Knut Tomas Dalen

• Bodin, Johanna Eva; Berg, Paul Ragnar; Dalen, Knut Tomas; Duale, Nur; Granquist, Erik Georg & Jevnaker, Anne-Marthe Ganes [Vis alle 19 forfattere av denne artikkelen] (2026). Guidance on the scientific information required for risk assessment of genetically modified animals intended for field trials in Norway. VKM Report. 2026(7), s. 1–68. Fulltekst i vitenarkiv Vis sammendrag

  The Norwegian Environment Agency has tasked The Norwegian Scientific Committee for Food and Environment (VKM) with developing generic guidance documents for environmental risk assessment of genetically modified organisms (GMOs) to be used in field trials. GMOs used in limited field trials may have effect on the environment, and human and animal health. All experiments involving the use of GMOs in field trails for research require approval under the Norwegian Gene Technology Act. The Norwegian Environment Agency is the decision-making authority for deliberate release of GM plants in field trials. VKM performs health and environmental risk assessments (ERAs) of GMOs for the Norwegian Environment Agency. This guidance document is intended as a support for applicants seeking approval for field trials under the Gene Technology Act and identifies the scientific documentation and data necessary to facilitate an ERA of a genetically modified animal (GM animal) conducted by VKM. The risk assessments conducted by VKM generally follow the step-by-step approach outlined in EU Directive 2001/18/EC on the deliberate release of genetically modified organisms into the environment, starting with hazard identification, hazard characterization, exposure characterization and risk characterization. The Gene Technology Act and the Regulations on impact assessment under the Gene Technology Act implements directive 2001/18/EC into Norwegian legislation. Appendix 2 of the Regulation contain the principles for environmental risk assessment, which corresponds to the principles of Annex II in the Directive. The European Food Safety Authority (EFSA) has developed further guidance on the risk assessment of genetically modified organisms based on Annex II. ERAs of GM animals involve the collection, assessment and, where appropriate, generation of information on a GM animal to determine its potential impacts on the environment and on human and animal health, compared with non-GM animals or appropriate comparators. VKM performs risk assessments that include the following six steps: hazard identification, hazard characterisation, exposure characterisation, risk characterisation, risk reducing measures, and overall risk evaluation of the use of the GM animal in a field trial. Applicants should identify the scientific documentation and data necessary for VKM to perform an ERA based on these steps. Applicants should also consider general risk reducing measures in relation to the identified risks, taking into consideration the type of GM animal, the intended management regime (confinement), the scale of the field trial, the characteristics of the genetic modification, the characteristics of the identified hazard(s), and the potential consequences for the environment and for human and animal health. This document provides guidance for the assessment of the potential environmental effects of GM animals, based on data from the required molecular characterisation, consideration of the potential impacts of the modified characteristics of the GM animal, and any risk mitigating measures implemented in the event of escape of GM animals into the environment during field trials. The guidance is intended as a dynamic document to be amended in accordance with future scientific and regulatory developments.

• Doncheva, Atanaska; Higa, Ryoko; Khanal, Prabhat; Ingebrigtsen, Martine Villemo Øksenvåg; Li, Yuchuan & Kolan, Shrikant [Vis alle 16 forfattere av denne artikkelen] (2025). Elevated adipose inflammation, but reduced hepatic triacylglycerol storage in diet-induced obese Plin4/mice. Journal of Biological Chemistry. ISSN 0021-9258. 302(2). doi: 10.1016/j.jbc.2025.111043. Fulltekst i vitenarkiv
• Dufour, Damien; Bryne, Sandra Kristine Stølen; Dapsance, Florian; Ferrito, Noemi; Plotton, Ingrid & Dalen, Knut Tomas [Vis alle 9 forfattere av denne artikkelen] (2025). Mechanisms of sexually dimorphic adipose tissue remodelling upon prolonged breastfeeding. bioRxiv (preprint article). doi: 10.1101/2025.09.05.674416. Fulltekst i vitenarkiv Vis sammendrag

  Early developmental cues exert lasting influence on the adipose tissue function and the metabolic health throughout adulthood. In mice, adipose tissue remodelling during the weaning transition programs long-term tissue plasticity, setting its capacity for expansion and thermogenesis in response to environmental stimuli. However, the mechanisms driving this remodelling, and the role of weaning-associated dietary changes in this process, are unknown. Here, we characterise the emergence of sexually dimorphic patterns of adipose tissue distribution and function during the post-weaning period. As subcutaneous adipocytes acquire a white phenotype, the tissue microenvironment undergoes a coordinated remodelling, including reduced innervation and an increase in immune cell content. Using a model of prolonged breastfeeding, we show that it promotes adipose tissue expansion through sex-dependent mechanisms, stimulating progenitor proliferation in males and adipocyte hypertrophy in females. In males, this is accompanied by accelerated tissue whitening, which we link to enhanced clearance of extracellular noradrenaline by mature adipocytes. Our findings reveal sex- and diet-dependent mechanisms governing adipose tissue maturation and highlight how early life nutritional cues shape the microenvironment and function of mature adipocytes. Highlights - The peri-weaning period associates with sexually dimorphic remodelling of the adipose tissue - Whitening of the adipose tissue associates with immune infiltration and decrease innervation in both sexes - Prolonged breastfeeding prevents drop in proliferation in males - Whitening is accelerated in males during prolonged breastfeeding

• Fosslie, Madeleine Lystad; Ilaslan, Erkut; Skuland, Trine; Choudalakis, Michel; Søegaard, Mirra Louise Cicilie & Halliwell, Jason Alexander [Vis alle 23 forfattere av denne artikkelen] (2025). Major waves of H2A.Z incorporation during mouse oogenesis and preimplantation embryo development. Nature Communications. 17(1). doi: 10.1038/s41467-025-66919-x. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Epigenomes of mammalian oocytes and embryos undergo major transitions essential for successful development. Here, we provide genome-wide maps of histone variant H2A.Z during twelve stages of mouse oogenesis and preimplantation embryo development and relate it to histone marks and genomic features. This revealed that major waves of H2A.Z incorporation occur early in growing oocytes, forming distinct patterns of maternal, embryonic, and persistent H2A.Z enrichment. Late maternal enrichment is inherited by the zygote and precedes reduced formation of lamina associated domains and early replication in the maternal genome of 2-cell embryos. Persistent H2A.Z enrichment is strongly associated with CpG islands and H3K4me3 near transcription start sites of active genes, but thousands of maternal and embryonic H2A.Z incorporation sites exist elsewhere, frequently at transposable elements. The persisting H2A.Z enrichments across related developmental stages enable preservation of epigenetic information despite major concurrent changes in H3K4me3, H3K27me3, and DNA methylation. Altogether, this advances our understanding of how histone variants contribute to epigenetic reprogramming during mammalian oogenesis and early development.

• Hindar, Kjetil; Bodin, Johanna Eva; Dalen, Knut Tomas; Duale, Nur; Garseth, Åse Helen & Malmstrøm, Martin [Vis alle 14 forfattere av denne artikkelen] (2025). Overview of methods for production of sterile salmonids, their applicability in aquaculture and possible implications to wild salmon populations and biodiversity in Norway. VKM Report. 2025(02), s. 1–92. doi: https:/vkm.no/risikovurderinger/allevurderinger/steriloppdrettsfiskeffekterpabiologiskmangfold.4.6b6641cb18a179b6780ab2db.html. Fulltekst i vitenarkiv Vis sammendrag

  VKM has assessed the positive and negative effects on biodiversity were sterile salmon to be used in Norwegian aquaculture. Triploidisation is assessed as the most effective method for sterilising fish, but it can affect the welfare and health of the fish. Several other techniques for producing sterile salmon are being tested, but it is too early to determine whether they can be used in large-scale farming. This is the key message in a knowledge summary VKM has prepared for the Norwegian Environment Agency. Background Escaped farmed salmon poses a major threat to wild salmon in Norway. hey can interbreed with wild salmon, genetically alter them, and make the populations less adaptable and more vulnerable to disease and environmental changes. A possible solution to the problem may be to use sterile salmon in farming. To date, only triploidisation has been tested. Newly fertilised eggs are given a hydrostatic pressure shock, thereby retaining an extra set of chromosomes which render the fish sterile. This method is currently the only one tested on a large scale. Triploidisation is effective but can also pose health and welfare challenges to fish. Methods VKM has reviewed available scientific literature regarding methods that can be used to produce sterile salmon. VKM has assessed whether these methods work as well, or better, than triploidy and whether they are likely to have fewer negative effects on fish welfare. Assessments have also been made of whether farmed fish treated with other sterilisation methods pose a greater or lesser threat to wild salmon than traditional farmed salmon. VKM has looked at the possibilities for further development of the triploidisation technique and has also assessed various methods currently being tested for producing sterile fish. Some of these are still at the laboratory-testing stage, while others are approaching trials with release into sea-pens. VKM has grouped the different methods based on whether they cause permanent changes in the genome (so-called "knock-out" of important genes) or whether the changes only result in temporary blocking or downregulation of gene expression (so-called "knock-down"). Results VKM concludes that triploidisation remains the most effective method and that there are possibilities to further develop this methodology through targeted breeding and adjustments in how the fish are kept. These measures can potentially solve the challenges for fish health and welfare. Using pure triploid female lines can also reduce some of the other challenges by preventing spawning interactions in rivers and reducing disease transmission to wild salmon. Alternative sterilisation methods, such as gene editing, vaccination, and temporary downregulation of proteins for gonad development using antisense oligomers and egg immersion, are promising but still under development. VKM assesses that methods causing permanent changes in the genome of diploid fish have a higher inherent risk than methods that only affect gene expression. Hope in egg-bathing Perhaps the most promising technique for safe production of sterile salmon is to add synthetic oligonucleotides to the eggs at an early stage, thereby preventing germ cell development without causing any inheritable changes. Such oligonucleotides can be injected into the eggs or absorbed by the eggs through bathing (immersion) in a special solution. "Especially the method involving targeted 'tools,' such as oligonucleotides that prevent germ cell development and can be added to the eggs in a water bath, seems promising," says Johanna Bodin, member of the Panel for Genetically Modified organisms and spokesperson for the report. (...)

• Pandey, Deepak; Doncheva, Atanaska Ivanova; Sapkota, Rumakanta; Jüterbock, Alexander Oliver; Viswanath, Kiron & Dalen, Knut Tomas [Vis alle 7 forfattere av denne artikkelen] (2025). Dietary inclusions of the brown macroalgae, Ascophyllum nodosum and Fucus vesiculosus, favourably modulate fat deposition and the caecal microbiome of obese mice. Food Bioscience. ISSN 2212-4292. 68. doi: 10.1016/j.fbio.2025.106590. Fulltekst i vitenarkiv Vis sammendrag

  Effective preventive measures are needed to lower the global incidence of obesity in humans. We investigated whether the dietary inclusions of brown macroalgae Ascophyllum nodosum (AN) or Fucus vesiculosus (FV) prevent diet-associated obesity development in mice by modulating the gut microbiome and body composition. Female C57BL/6J mice were fed a low-fat control, high-fat (HF), or HF diet with 5 % inclusion of whole AN or FV biomass for 12 weeks. Body composition, whole-body energy metabolism, caecal microbiome, and liver transcriptomics were evaluated. Mice fed AN and FV-added HF diets had lower gonadal (∼30 %), subcutaneous (∼25 %), and total (∼40 %) fat mass compared to the mice fed the HF diet, although the differences were statistically non-significant. Macroalgae-supplemented diet groups had reduced Firmicutes: Bacteroidota ratios and lower abundances of obesity-associated bacterial genera, including Lachnoclostridium, Lachnospiraceae, Lactococcus, Romboutsia, and Tuzzerella in the caecal contents, compared to the HF diet group (more prominently with FV-supplementation). These bacteria were found to be positively associated with fat mass gain. On the other hand, macroalgal addition promoted certain leanness-associated and short-chain fatty acids-producing bacteria, where FV-addition most prominently enriched Alistipes, Akkermansia, Muribaculum, and Oscillospiraceae NK4A214 group, while AN-addition highly promoted the Bacteroides. This study shows that dietary inclusion of AN or FV in the HF diet promotes a unique and healthier gut microbiota and lowers the HF diet-associated fat mass gain in mice.

• Higa, Ryoko; Pourteymour, Shirin; Kolan, Pratibha Shrikant; Dankel, Simon N; Fernø, Johan & Mellgren, Gunnar [Vis alle 12 forfattere av denne artikkelen] (2025). Hepatic lipid metabolism is altered in Ubiad1+/- mice of both sexes. Scientific Reports. 15. doi: 10.1038/s41598-025-91283-7. Fulltekst i vitenarkiv Vis sammendrag

  UbiA prenyltransferase domain containing 1 (Ubiad1) has the potential to affect cholesterol and phospholipid levels in different cell types. We previously identified Ubiad1 as a candidate gene for regulating subcutaneous fat pad weight in a mouse genome-wide association study. Here we evaluated the relationship between Ubiad1 and obesity-related traits in cohorts of humans and mice, and in Ubiad1+/− mice fed a high-fat diet. In both humans and mice, adipose tissue Ubiad1 mRNA expression correlated negatively with adiposity and positively with mitochondria-related genes. To determine the role of Ubiad1 in high-fat diet-induced obesity, we disrupted the Ubiad1 gene in mice. Deletion of Ubiad1 was embryonically lethal in C57BL/6 N mice, preventing analysis of adult Ubiad1−/− mice. Thus, male and female Ubiad1+/+ and Ubiad1+/− mice were fed high-fat diet for 10 weeks, with no difference in weight gain and adipose tissue organ weights observed between the genotypes. Analysis of liver mRNA expression revealed that Ubiad1 heterozygosis (Ubiad1+/−) altered several pathways involved in lipid metabolism. Detailed lipid quantification with HPLC-qTOF/MS showed increased levels of hepatic ceramides in female Ubiad1+/− mice, whereas phosphatidylglycerols, phosohatidylinositol and lysophosphatidylethanolamines were reduced in male Ubiad1+/− mice. Our findings reveal sex-specific effects of Ubiad1 expression on hepatic lipid metabolism.

• Medin, Anine Christine; Andersen, Lene Frost; Fadnes, Lars Thore; Lillegaard, Inger Therese Laugsand; Madsen, Lise & Mangschou, Bente [Vis alle 12 forfattere av denne artikkelen] (2024). Beregning og vurdering av i hvilken grad høringsutkast til nye kostråd vil dekke behov og anbefalinger for næringsstoffer. VKM Report. 2024(6), s. 1–79. Fulltekst i vitenarkiv Vis sammendrag

  Vitenskapskomiteen for mat og miljø (VKM) har vurdert om Helsedirektoratets høringsutkast til nye kostråd fra 22. mars dekker næringsstoffanbefalingene for voksne, inkludert gravide og ammende.' Oppdraget er gitt av Helsedirektoratet, som en del av arbeidet med å revidere kostrådene, og VKMs beregninger og vurderinger er basert på høringsutkastet. VKMs rapport med resultatene fra oppdraget publiseres samtidig som kostrådene. VKMs rapport og konklusjonerne som presenteres gjelder høringsutkast til kostråd, slik de forelå 22. mars 2024. Basert på VKMs arbeid, har Helsedirektoratet valgt å justere enkelte av kostrådene, slik at kritiske næringsstoffer vil dekkes bedre i de endelige kostrådene som ble publiseres 15. august, parallelt med publisering av VKMs rapport. Hovedkonklusjon fra VKMs rapport: VKM konkluderer at et kosthold i tråd med høringsutkastet til nye kostråd sannsynligvis kan være tilstrekkelig for å dekke næringsstoffanbefalingene for de fleste vitaminer og mineraler for de fleste voksne, med noen unntak. Vurderingen omfatter to scenarioer – lavt og høyt – basert på utkast til kostrådene. Disse to scenarioene representerer henholdsvis de laveste og høyeste mengdene av matvaregruppene som omfattes av utkastet til kostrådene; lavt kostrådsscenario og høyt kostrådsscenario. VKM har kun beregnet næringsinnholdet for maten fra mengdene i utkast til kostråd, ikke for det totale kostholdet. –Vi har vurdert om næringsinnholdet dekkes hvis man følger de foreslåtte kostrådene, slik de forelå i mars. Vi konkluderer med at å følge disse sannsynligvis kan være tilstrekkelig for å dekke næringsstoffanbefalingene for de fleste vitaminer og mineraler for de fleste voksne, hvis man spiser et kosthold basert på de høyeste mengdene av matvaregruppene i kostrådsutkastet, sier faglig leder Anine Medin, som har ledet VKMs arbeid. VKMs resultater viser at innholdet av de fleste beregnede vitaminer og mineraler synes å være tilstrekkelig for kvinner og menn i alle aldere ved et kosthold i tråd med høyt kostrådsscenario. Innholdet av vitamin D, kalsium (kun unge voksne), jern (kun kvinner i fertil alder), sink (kun menn) og selen vil imidlertid sannsynligvis kunne være for lavt for en mindre andel kvinner og menn ved et kosthold som tilsvarer høyt scenario. Beregningene viser at i et kosthold i tråd med lavt kostrådsscenario, ligger innholdet av flere næringsstoffer lavere enn i høyt scenario. Innholdet av riboflavin, kalsium, jern (kun kvinner i fertil alder), sink, jod og selen vil sannsynligvis kunne være for lavt for en betydelig andel kvinner og menn ved et kosthold som tilsvarer lavt scenario. Videre vil innholdet av vitamin D, vitamin B6, folat, kalium, og jern (kun menn) kunne være for lavt for en mindre andel kvinner og menn. Gravide og ammende står i en særstilling, fordi de har høyere behov for næringsstoffer enn den øvrige befolkningen. Slik er beregningene og vurderingene gjort VKM har laget to kostrådsscenarioer basert på mengder av ulike matvaregrupper, som er gitt i høringsutkastet eller som tilleggsinformasjon fra Helsedirektoratet underveis i arbeidet med rapporten. Eksempelvis inneholder det lave scenarioet 500 gram frukt og grønnsaker, mens det høye scenarioet inneholder 800 gram. Det lave scenarioet inneholder ikke egg, ost eller rødt kjøtt, mens høyt scenario inneholder ett egg om dagen, to osteskiver om dagen og 350 gram rødt kjøtt i uken. Begge scenarioene inneholder eksempelvis også 90 gram fullkorn per dag. Valget av matvarer fra matvaregruppene som er inkludert i scenarioene er basert på ordlyden i kostrådene, samt innsikt fra nasjonale kostholdsundersøkelser. For å vurdere sannsynligheten til om disse scenariene inneholder tilstrekkelig med næringsstoffer, har VKM vurdert dem opp mot næringsstoffanbefalingene.

• Dalen, Knut Tomas & Li, Yuchuan (2024). Regulation of lipid droplets and cholesterol metabolism in adrenal cortical cells. Vitamines and Hormones. ISSN 0083-6729. 124, s. 79–136. doi: 10.1016/bs.vh.2023.06.007. Fulltekst i vitenarkiv
• Chau, Khac Thanh Phong; Ryan, Elin; Dalen, Knut Tomas & Haugen, Fred (2024). Timing of acute cold exposure determines UCP1 and FGF21 expression - Possible interactions between the thermal environment, thermoregulatory responses, and peripheral clocks. Journal of Thermal Biology. ISSN 0306-4565. 124. doi: 10.1016/j.jtherbio.2024.103938. Fulltekst i vitenarkiv Vis sammendrag

  Thermoregulation is synchronized across the circadian cycle to uphold thermal homeostasis. To test if time-of-day matters for the response to environmental cold exposure, mice were acclimated to thermoneutrality (27 °C) for 2 months were subjected acutely (8 h) to cold ambient conditions (15 °C), whereas controls were maintained at thermoneutral conditions. The thermal exposure was tested in separate groups (N = 8) at three distinct time-of-day periods: in the LIGHT phase (L); the DARK phase (D); and a mix of the two (D + L). The magnitude of UCP1 protein and mRNA induction in brown adipose tissue (BAT) in response to acute cold exposure was time-of-day sensitive, peaking in LIGHT, whereas lower induction levels were observed in D + L, and DARK. Plasma levels of FGF21 were induced 3-fold by acute cold exposure at LIGHT and D + L, compared to the time-matched thermoneutral controls, whereas cold in DARK did not cause a significant increase of FGF21 plasma levels. Cold exposure affected, in BAT, the temporal mRNA expression patterns of core circadian clock components: Bmal1, Clock, Per1, Per3, Cry1, Cry2 Nr1d1, and Nr1d2, but in the liver, none of the transcripts were modified. Behavioral assessment using the Thermal Gradient Test (TGT) showed that acute cold exposure reduced cold sensitivity in D + L, but not in DARK. RNA-seq analyses of somatosensory neurons in DRG highlighted the role of the core circadian components in these cells, as well as transcriptional changes due to acute cold exposure. This elucidates the sensory system as a gauge and potential regulator of thermoregulatory responses based on circadian physiology. In conclusion, acute cold exposure elicits time-of-day specific effects on thermoregulatory pathways, which may involve underlying changes in thermal perception. These results have implications for efforts aimed at reducing risks associated with the organization of shift work in cold environments.

• Seferi, Gezime; Mjønes, Harald Stranger; Havik, Mona; Reiersen, Herman; Dalen, Knut Tomas & Nordengen, Kaja [Vis alle 7 forfattere av denne artikkelen] (2024). Distribution of lipid droplets in hippocampal neurons and microglia: impact of diabetes and exercise. Life Science Alliance (LSA). 7(10). doi: 10.26508/lsa.202302239. Fulltekst i vitenarkiv Vis sammendrag

  Neuroinflammation, aging, and neurodegenerative disorders are associated with excessive accumulation of neutral lipids in lipid droplets (LDs) in microglia. Type 2 diabetes mellitus (T2DM) may cause neuroinflammation and is a risk factor for neurodegenerative disorders. Here, we show that hippocampal pyramidal neurons contain smaller, more abundant LDs than their neighboring microglia. The density of LDs varied between pyramidal cells in adjacent subregions, with CA3 neurons containing more LDs than CA1 neurons. Within the CA3 region, a gradual increase in the LD content along the pyramidal layer from the hilus toward CA2 was observed. Interestingly, the high neuronal LD content correlated with less ramified microglial morphotypes. Using the db/db model of T2DM, we demonstrated that diabetes increased the number of LDs per microglial cell without affecting the neuronal LD density. High-intensity interval exercise induced smaller changes in the number of LDs in microglia but was not sufficient to counteract the diabetes-induced changes in LD accumulation. The changes observed in response to T2DM may contribute to the cerebral effects of T2DM and provide a mechanistic link between T2DM and neurodegenerative disorders.

• Li, Yanjiao; Wang, Yunhao; Vera-Rodriguez, Maria; Lindeman, Leif Christopher; Skuggen, Linda Ellevog & Rasmussen, Erik Magne Koscielniak [Vis alle 21 forfattere av denne artikkelen] (2023). Single-cell m6A mapping in vivo using picoMeRIP–seq. Nature Biotechnology. ISSN 1087-0156. doi: 10.1038/s41587-023-01831-7. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Current N 6 -methyladenosine (m 6 A) mapping methods need large amounts of RNA or are limited to cultured cells. Through optimized sample recovery and signal-to-noise ratio, we developed picogram-scale m 6 A RNA immunoprecipitation and sequencing (picoMeRIP–seq) for studying m 6 A in vivo in single cells and scarce cell types using standard laboratory equipment. We benchmark m 6 A mapping on titrations of poly(A) RNA and embryonic stem cells and in single zebrafish zygotes, mouse oocytes and embryos.

• Bodin, Johanna Eva; Aakre, Inger; Alexander, Jan; Mangschou, Bente; Parr, Christine Louise & Andersen, Lene Frost [Vis alle 15 forfattere av denne artikkelen] (2023). Risk assessment of hyaluronic acid in food supplements. VKM Report. 13, s. 1–70. Fulltekst i vitenarkiv Vis sammendrag

  Hyaluronic acid (HA) is a high-molecular-mass polysaccharide, that is endogenously produced and present in connective tissue, synovial fluid, intraoccular fluid, and skin. The basic unit of the HA polymer consists of D-glucuronic acid and N-acetyl-D-glucosamine. The Norwegian Food Safety Authority has requested VKM to evaluate the risk of adverse effects related to daily intake of food supplements with 150 mg, 120 mg, 64 mg, and 48 mg HA. Exposure from other sources of HA (food, cosmetics, and different medical applications) is not estimated.

• Meen, Astri Jeanette; Doncheva, Atanaska Ivanova; Böttcher, Yvonne; Dankel, Simon N; Hoffmann, Anne & Blüher, Matthias [Vis alle 16 forfattere av denne artikkelen] (2023). Obesity Is Associated with Distorted Proteoglycan Expression in Adipose Tissue. International Journal of Molecular Sciences. ISSN 1661-6596. 24(8). doi: 10.3390/ijms24086884. Fulltekst i vitenarkiv Vis sammendrag

  Proteoglycans are central components of the extracellular matrix (ECM) and binding partners for inflammatory chemokines. Morphological differences in the ECM and increased inflammation are prominent features of the white adipose tissues in patients with obesity. The impact of obesity and weight loss on the expression of specific proteoglycans in adipose tissue is not well known. This study aimed to investigate the relationship between adiposity and proteoglycan expression. We analyzed transcriptomic data from two human bariatric surgery cohorts. In addition, RT-qPCR was performed on adipose tissues from female and male mice fed a high-fat diet. Both visceral and subcutaneous adipose tissue depots were analyzed. Adipose mRNA expression of specific proteoglycans, proteoglycan biosynthetic enzymes, proteoglycan partner molecules, and other ECM-related proteins were altered in both human cohorts. We consistently observed more profound alterations in gene expression of ECM targets in the visceral adipose tissues after surgery (among others VCAN (p = 0.000309), OGN (p = 0.000976), GPC4 (p = 0.00525), COL1A1 (p = 0.00221)). Further, gene analyses in mice revealed sex differences in these two tissue compartments in obese mice. We suggest that adipose tissue repair is still in progress long after surgery, which may reflect challenges in remodeling increased adipose tissues. This study can provide the basis for more mechanistic studies on the role of proteoglycans in adipose tissues in obesity.

• Li, Yuchuan; Amrutkar, Manoj; Finstadsveen, Anette V.; Dalen, Knut Tomas; Verbeke, Caroline Sophie & Gladhaug, Ivar Prydz (2023). Fatty acids abrogate the growth-suppressive effects induced by inhibition of cholesterol flux in pancreatic cancer cells. Cancer Cell International. 23. doi: 10.1186/s12935-023-03138-8. Fulltekst i vitenarkiv Vis sammendrag

  Background Despite therapeutic advances, the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains extremely poor. Metabolic reprogramming is increasingly recognized as a key contributor to tumor progression and therapy resistance in PDAC. One of the main metabolic changes essential for tumor growth is altered cholesterol flux. Targeting cholesterol flux appears an attractive therapeutic approach, however, the complex regulation of cholesterol balance in PDAC cells remains poorly understood. Methods The lipid content in human pancreatic duct epithelial (HPDE) cells and human PDAC cell lines (BxPC-3, MIA PaCa-2, and PANC-1) was determined. Cells exposed to eight different inhibitors targeting different regulators of lipid flux, in the presence or absence of oleic acid (OA) stimulation were assessed for changes in viability, proliferation, migration, and invasion. Intracellular content and distribution of cholesterol was assessed. Lastly, proteome profiling of PANC-1 exposed to the sterol O-acyltransferase 1 (SOAT1) inhibitor avasimibe, in presence or absence of OA, was performed. Results PDAC cells contain more free cholesterol but less cholesteryl esters and lipid droplets than HPDE cells. Exposure to different lipid flux inhibitors increased cell death and suppressed proliferation, with different efficiency in the tested PDAC cell lines. Avasimibe had the strongest ability to suppress proliferation across the three PDAC cell lines. All inhibitors showing cell suppressive effect disturbed intracellular cholesterol flux and increased cholesterol aggregation. OA improved overall cholesterol balance, reduced free cholesterol aggregation, and reversed cell death induced by the inhibitors. Treatment with avasimibe changed the cellular proteome substantially, mainly for proteins related to biosynthesis and metabolism of lipids and fatty acids, apoptosis, and cell adhesion. Most of these changes were restored by OA. Conclusions The study reveals that disturbing the cholesterol flux by inhibiting the actions of its key regulators can yield growth suppressive effects on PDAC cells. The presence of fatty acids restores intracellular cholesterol balance and abrogates the alternations induced by cholesterol flux inhibitors. Taken together, targeting cholesterol flux might be an attractive strategy to develop new therapeutics against PDAC. However, the impact of fatty acids in the tumor microenvironment must be taken into consideration.

• Doncheva, Atanaska Ivanova; Li, Yuchuan; Khanal, Prabhat; Hjorth, Marit; Kolset, Svein Olav & Norheim, Frode Amador [Vis alle 8 forfattere av denne artikkelen] (2023). Altered hepatic lipid droplet morphology and lipid metabolism in fasted Plin2-null mice. Journal of Lipid Research. ISSN 0022-2275. 64(12). doi: 10.1016/j.jlr.2023.100461. Fulltekst i vitenarkiv Vis sammendrag

  Perilipin 2 (Plin2) binds to the surface of hepatic lipid droplets (LDs) with expression levels that correlate with triacylglyceride (TAG) content. We investigated if Plin2 is important for hepatic LD storage in fasted or high-fat diet-induced obese Plin2+/+ and Plin2−/− mice. Plin2−/− mice had comparable body weights, metabolic phenotype, glucose tolerance, and circulating TAG and total cholesterol levels compared with Plin2+/+ mice, regardless of the dietary regime. Both fasted and high-fat fed Plin2−/− mice stored reduced levels of hepatic TAG compared with Plin2+/+ mice. Fasted Plin2−/− mice stored fewer but larger hepatic LDs compared with Plin2+/+ mice. Detailed hepatic lipid analysis showed substantial reductions in accumulated TAG species in fasted Plin2−/− mice compared with Plin2+/+ mice, whereas cholesteryl esters and phosphatidylcholines were increased. RNA-Seq revealed minor differences in hepatic gene expression between fed Plin2+/+ and Plin2−/− mice, in contrast to marked differences in gene expression between fasted Plin2+/+ and Plin2−/− mice. Our findings demonstrate that Plin2 is required to regulate hepatic LD size and storage of neutral lipid species in the fasted state, while its role in obesity-induced steatosis is less clear.

• Wang, Yunhao; Li, Yanjiao; Skuland, Trine; Zhou, Chengjie; Li, Aifu & Hashim, Adnan [Vis alle 13 forfattere av denne artikkelen] (2023). The RNA m6A landscape of mouse oocytes and preimplantation embryos. Nature Structural & Molecular Biology. ISSN 1545-9993. 30(5), s. 703–709. doi: 10.1038/s41594-023-00969-x. Fulltekst i vitenarkiv Vis sammendrag

  Despite the significance of N6-methyladenosine (m6A) in gene regulation, the requirement for large amounts of RNA has hindered m6A profiling in mammalian early embryos. Here we apply low-input methyl RNA immunoprecipitation and sequencing to map m6A in mouse oocytes and preimplantation embryos. We define the landscape of m6A during the maternal-to-zygotic transition, including stage-specifically expressed transcription factors essential for cell fate determination. Both the maternally inherited transcripts to be degraded post fertilization and the zygotically activated genes during zygotic genome activation are widely marked by m6A. In contrast to m6A-marked zygotic ally-activated genes, m6A-marked maternally inherited transcripts have a higher tendency to be targeted by microRNAs. Moreover, RNAs derived from retrotransposons, such as MTA that is maternally expressed and MERVL that is transcriptionally activated at the two-cell stage, are largely marked by m6A. Our results provide a foundation for future studies exploring the regulatory roles of m6A in mammalian early embryonic development.

• Hindar, Kjetil; Bodin, Johanna Eva; Duale, Nur; Jevnaker, Anne-Marthe Ganes; Garseth, Åse Helen & Malmstrøm, Martin [Vis alle 15 forfattere av denne artikkelen] (2023). Environmental risk assessment of genetically modified sterile VIRGIN® Atlantic salmon for use in research trials in aquaculture sea-cages. VKM Report. 2023:20, s. 1–94. Fulltekst i vitenarkiv Vis sammendrag

  One of the substantial environmental challenges posed by the aquaculture industry is the escape of farmed Atlantic salmon (Salmo salar), which can mate with wild Atlantic salmon and alter the genetic composition of the wild populations. One potential solution to mitigate this issue is the cultivation of sterile salmon in aquaculture. Atlantic salmon can be made sterile by pressure or temperature treatment of newly fertilized eggs to produce triploids, which are functionally sterile due to their unpaired chromosomes. However, these triploids often perform poorly on commercial fish farms and the production of triploid salmon in Norway is put on hold due to welfare issues of the fish.

• Pourteymour, Shirin; Drevon, Christian André; Dalen, Knut Tomas & Norheim, Frode Amador (2023). Mechanisms Behind NAFLD: a System Genetics Perspective. Current Atherosclerosis Reports. ISSN 1523-3804. 25(11), s. 869–878. doi: 10.1007/s11883-023-01158-3. Fulltekst i vitenarkiv
• Doncheva, Atanaska Ivanova; Romero, Silvana Angelica Troncoso; Ramirez-Garrastacho, Manuel; Lee-Ødegård, Sindre; Kolnes, Kristoffer Jensen & Tangen, Daniel S. [Vis alle 11 forfattere av denne artikkelen] (2022). Extracellular vesicles and microRNAs are altered in response to exercise, insulin sensitivity and overweight. Acta Physiologica. ISSN 1748-1708. 236(4). doi: 10.1111/apha.13862. Fulltekst i vitenarkiv Vis sammendrag

  Abstract: Extracellular vesicles induced by exercise have emerged as potential mediators of tissue crosstalk. Extracellular vesicles and their cargo miRNAs have been linked to dysglycemia and obesity in animal models, but their role in humans is unclear. Aim: The aim of the study was to characterize the miRNA content in plasma extracellular vesicle isolates after acute and long-term exercise and to study associations between extracellular vesicle miRNAs, mRNA expression in skeletal muscle and adipose tissue, and cardiometabolic risk factors. Methods: Sedentary men with or without dysglycemia and overweight underwent an acute bicycle test and a 12-week exercise intervention with extensive metabolic phenotyping. Gene expression in m. vastus lateralis and subcutaneous adipose tissue was measured with RNA sequencing. Extracellular vesicles were purified from plasma with membrane affinity columns or size exclusion chromatography. Results: Extracellular vesicle miRNA profiling revealed a transient increase in the number of miRNAs after acute exercise. We identified miRNAs, such as miR-652-3p, that were associated to insulin sensitivity and adiposity. By performing explorative association analyses, we identified two miRNAs, miR-32-5p and miR-339-3p, that were strongly correlated to an adipose tissue macrophage signature. Conclusion: Numerous miRNAs in plasma extracellular vesicle isolates were increased by exercise, and several miRNAs correlated to insulin sensitivity and adiposity. Our findings warrant future studies to characterize exercise-induced extracellular vesicles and cargo miRNA to clarify where exercise-induced extracellular vesicles originate from, and to determine whether they influence metabolic health or exercise adaptation.

• Hjorth, Marit; Galigniana, Natalia; Ween, Ola; Ulven, Stine Marie; Holven, Kirsten Bjørklund & Dalen, Knut Tomas [Vis alle 7 forfattere av denne artikkelen] (2022). Postprandial Effects of Salmon Fishmeal and Whey on Metabolic Markers in Serum and Gene Expression in Liver Cells. Nutrients. 14(8). doi: 10.3390/nu14081593. Fulltekst i vitenarkiv Vis sammendrag

  Fish is considered an important part of a healthy diet, in part due to the content of long chain omega-3 fatty acids. However, both lean and fatty fish have beneficial health effects, suggesting that micronutrients and proteins may play a role. In a randomised, controlled, cross-over trial, five healthy male participants consumed 5.2 g of protein from either salmon fishmeal or whey. Blood samples were taken before and 30 and 60 min after intake. The concentration of glucose, lipids, hormones and metabolites, including 28 different amino acids and derivatives, were measured in serum or plasma. Cultured HepG2 cells were incubated with or without serum from the participants, and transcriptomic profiling was performed using RNA sequencing. The ingestion of both salmon fishmeal and whey reduced the glucose and triglyceride levels in serum. Protein intake, independent of the source, increased the concentration of 22 amino acids and derivatives in serum. Fishmeal increased the concentration of arginine, methionine, serine, glycine, cystathionine and 2-aminobutyric acid more than whey did. Incubation with postprandial serum resulted in large transcriptomic alterations in serum-fasted HepG2 cells, with the differential expression of >4500 protein coding genes. However, when comparing cells cultivated in fasting serum to postprandial serum after the ingestion of fishmeal and whey, we did not detect any differentially regulated genes, neither with respect to the protein source nor with respect to the time after the meal. The comparable nutrigenomic effects of fishmeal and whey do not change the relevance of fish by-products as an alternative food source.

• Canet, Francisco; Christensen, Jacob J.; Victor, Victor M.; Hustad, Kristin Solheim; Ottestad, Inger & Rundblad, Amanda [Vis alle 11 forfattere av denne artikkelen] (2022). Glycated proteins, glycine, acetate, and monounsaturated fatty acids may act as new biomarkers to predict the progression of type 2 diabetes: Secondary analyses of a randomized controlled trial. Nutrients. 14(23), s. 1–19. doi: 10.3390/nu14235165. Fulltekst i vitenarkiv Vis sammendrag

  Food protein or food-derived peptides may regulate blood glucose levels; however, studies have shown inconsistent results. The aim of the present study was to characterize subgroups of individuals with increased risk of type 2 diabetes (T2D) and to investigate the cardiometabolic effects of fish protein in the same subgroups. We first divided participants into high insuliniAUC and low insuliniAUC subjects based on their insulin incremental area under the curve (iAUC) levels after a 2 h oral glucose tolerance test (OGTT), and secondly based on whether they had received 5.2 g salmon fish protein or placebo for 8 weeks, in a previously conducted randomized controlled trial (RCT). We then profiled these groups by analyzing plasma metabolomics and peripheral blood mononuclear cell (PBMC) gene expression. Compared to the low insuliniAUC group, the high insuliniAUC group had higher plasma concentrations of monounsaturated fatty acids (MUFAs) and glycated proteins (GlycA) and lower concentrations of glycine and acetate. After intervention with fish protein compared to placebo, however, only acetate was significantly increased in the low insuliniAUC group. In conclusion, we identified metabolic biomarkers known to be associated with T2D; also, intervention with fish protein did not affect cardiometabolic risk markers in subgroups with increased risk of T2D.

• Torp, May-Kristin; Ranheim, Trine; Schjalm, Camilla; Hjorth, Marit; Heiestad, Christina Mathisen & Dalen, Knut Tomas [Vis alle 13 forfattere av denne artikkelen] (2022). Intracellular Complement Component 3 Attenuated Ischemia-Reperfusion Injury in the Isolated Buffer-Perfused Mouse Heart and Is Associated With Improved Metabolic Homeostasis. Frontiers in Immunology. 13. doi: 10.3389/fimmu.2022.870811. Fulltekst i vitenarkiv Vis sammendrag

  The innate immune system is rapidly activated during myocardial infarction and blockade of extracellular complement system reduces infarct size. Intracellular complement, however, appears to be closely linked to metabolic pathways and its role in ischemia-reperfusion injury is unknown and may be different from complement activation in the circulation. The purpose of the present study was to investigate the role of intracellular complement in isolated, retrogradely buffer-perfused hearts and cardiac cells from adult male wild type mice (WT) and from adult male mice with knockout of complement component 3 (C3KO). Main findings: (i) Intracellular C3 protein was expressed in isolated cardiomyocytes and in whole hearts, (ii) after ischemia-reperfusion injury, C3KO hearts had larger infarct size (32 ± 9% in C3KO vs. 22 ± 7% in WT; p=0.008) and impaired post-ischemic relaxation compared to WT hearts, (iii) C3KO cardiomyocytes had lower basal oxidative respiration compared to WT cardiomyocytes, (iv) blocking mTOR decreased Akt phosphorylation in WT, but not in C3KO cardiomyocytes, (v) after ischemia, WT hearts had higher levels of ATP, but lower levels of both reduced and oxidized nicotinamide adenine dinucleotide (NADH and NAD+, respectively) compared to C3KO hearts. Conclusion: intracellular C3 protected the heart against ischemia-reperfusion injury, possibly due to its role in metabolic pathways important for energy production and cell survival.

• Hjorth, Marit; Doncheva, Atanaska Ivanova; Norheim, Frode Amador; Ulven, Stine Marie; Holven, Kirsten Bjørklund & Sæther, Thomas [Vis alle 7 forfattere av denne artikkelen] (2022). Consumption of salmon fishmeal increases hepatic cholesterol content in obese C57BL/6 J mice. European Journal of Nutrition. ISSN 1436-6207. 61, s. 4027–4043. doi: 10.1007/s00394-022-02930-y. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Purpose By-products from farmed fish contain large amounts of proteins and may be used for human consumption. The purpose of this study was to investigate cardiometabolic effects and metabolic tolerance in mice consuming fishmeal from salmon by-products, salmon filet or beef. Methods Female C57BL/6J mice were fed chow, as a healthy reference group, or a high-fat diet for 10 weeks to induce obesity and glucose intolerance. Obese mice were subsequently given isocaloric diets containing 50% of the dietary protein from salmon fishmeal, salmon filet or beef for 10 weeks. Mice were subjected to metabolic phenotyping, which included measurements of body composition, energy metabolism in metabolic cages and glucose tolerance. Lipid content and markers of hepatic toxicity were determined in plasma and liver. Hepatic gene and protein expression was determined with RNA sequencing and immunoblotting. Results Mice fed fishmeal, salmon filet or beef had similar food intake, energy consumption, body weight gain, adiposity, glucose tolerance and circulating levels of lipids and hepatic toxicity markers, such as p-ALT and p-AST. Fishmeal increased hepatic cholesterol levels by 35–36% as compared to salmon filet (p = 0.0001) and beef (p = 0.005). This was accompanied by repressed expression of genes involved in steroid and cholesterol metabolism and reduced levels of circulating Pcsk9. Conclusion Salmon fishmeal was well tolerated, but increased hepatic cholesterol content. The high cholesterol content in fishmeal may be responsible for the effects on hepatic cholesterol metabolism. Before introducing fishmeal from salmon by-products as a dietary component, it may be advantageous to reduce the cholesterol content in fishmeal. Introduction

• Bodin, Johanna Eva; Thorstensen, Tage; Alsheikh, Muath K; Basic, Dean; Edvardsen, Rolf Brudvik & Dalen, Knut Tomas [Vis alle 41 forfattere av denne artikkelen] (2021). Genome editing in food and feed production – implications for risk assessment. Scientific Opinion of the Scientific Steering Committee of the Norwegian Scientific Committee for Food and Environment. VKM Report. 2021(18). Fulltekst i vitenarkiv Vis sammendrag

  The Norwegian Scientific Committee for Food and Environment (VKM) initiated this work to examine the extent to which organisms developed by genome-editing technologies pose new challenges in terms of risk assessment. This report considers whether the risk assessment guidance on genetically modified organisms, developed by the European Food Safety Authority (EFSA), can be applied to evaluate potential risks of organisms developed by genome editing. Background Gene technology has allowed for the transfer of genes between organisms and species, and thereby to design altered genotypes with novel traits, i.e. GMOs. A new paradigm started in the early 2000s with the development of genome-editing techniques. Unlike traditional genetic modification techniques resulting in insertion of foreign DNA fragments at random locations in the genome, the new genome-editing techniques additionally open for a few single nucleotide edits or short insertions/deletions at a targeted site in an organism’s genome. These new techniques can be applied to most types of organisms, including plants, animals and microorganisms of commercial interest. An important question is how the novel, genome-edited organisms should be evaluated with respect to risks to health and the environment. The European Court of Justice decided in 2018 to include genome-edited organisms in the GMO definition and hence in the regulatory system already in place. This implies that all products developed by genome-editing techniques must be risk-assessed within the existing regulatory framework for GMOs. The European and Norwegian regulatory frameworks regulate the production, import and placing on the market of food and feed containing, consisting of or produced from GMOs, as well as the release of GMOs into the environment. The assessment draws on guidance documents originally developed by EFSA for risk assessment of GMOs, which were drawn up mainly to address risks regarding insertion of transgenes. The new genome-editing techniques, however, provide a new continuum of organisms ranging from those only containing a minor genetic alteration to organisms containing insertion or deletion of larger genomic regions. Risk assessment of organisms developed by genome editing The present discourse on how new genome-editing techniques should be regulated lacks an analysis of whether risk assessment methodologies for GMOs are adequate for risk assessment of organisms developed through the use of the new genome-editing techniques. Therefore, this report describes the use of genome-editing techniques in food and feed production and discusses challenges in risk assessment with the regulatory framework. Specifically, this report poses the question as to whether the EFSA guidance documents are sufficient for evaluating risks to health and environment posed by genome-edited plants, animals and microorganisms. To address these questions, the report makes use of case examples relevant for Norway. These examples, intended for food and feed, include oilseed rape with a modified fatty acid profile, herbicide-tolerant and pest-resistant crops, sterile salmon, virus-resistant pigs and hornless cattle. The report considers all aspects of the stepwise approach as described in the EFSA guidance documents. Conclusions The inherent flexibility of the EFSA guidance makes it suitable to cover health and environmental risk assessments of a wide range of organisms with various traits and intended uses. Combined with the embedded case-by-case approach the guidance is applicable to genome-edited organisms. The evaluation of the guidance demonstrates that the parts of the health and environmental risk assessment concerned with novel traits (i.e. the phenotype of the organism) may be fully applied to all categories of genome-edited organisms. ............

• Doncheva, Atanaska Ivanova; Norheim, Frode Amador; Hjorth, Marit; Grujic, Mirjana; Paivandy, Aida & Dankel, Simon N [Vis alle 14 forfattere av denne artikkelen] (2021). Serglycin Is Involved in Adipose Tissue Inflammation in Obesity. Journal of Immunology. ISSN 0022-1767. 208(1), s. 121–132. doi: 10.4049/jimmunol.2100231. Fulltekst i vitenarkiv Vis sammendrag

  Chronic local inflammation of adipose tissue is an important feature of obesity. Serglycin is a proteoglycan highly expressed by various immune cell types known to infiltrate adipose tissue under obese conditions. To investigate if serglycin expression has an impact on diet-induced adipose tissue inflammation, we subjected Srgn+/+ and Srgn−/− mice (C57BL/6J genetic background) to an 8-wk high-fat and high-sucrose diet. The total body weight was the same in Srgn+/+ and Srgn−/− mice after diet treatment. Expression of white adipose tissue genes linked to inflammatory pathways were lower in Srgn−/− mice. We also noted reduced total macrophage abundance, a reduced proportion of proinflammatory M1 macrophages, and reduced formation of crown-like structures in adipose tissue of Srgn−/− compared with Srgn+/+ mice. Further, Srgn−/− mice had more medium-sized adipocytes and fewer large adipocytes. Differentiation of preadipocytes into adipocytes (3T3-L1) was accompanied by reduced Srgn mRNA expression. In line with this, analysis of single-cell RNA sequencing data from mouse and human adipose tissue supports that Srgn mRNA is predominantly expressed by various immune cells, with low expression in adipocytes. Srgn mRNA expression was higher in obese compared with lean humans and mice, accompanied by an increased expression of immune cell gene markers. SRGN and inflammatory marker mRNA expression was reduced upon substantial weight loss in patients after bariatric surgery. Taken together, this study introduces a role for serglycin in the regulation of obesity-induced adipose inflammation.

• Li, Yuchuan; Khanal, Prabhat; Norheim, Frode; Hjorth, Marit; Bjellaas, Thomas & Drevon, Christian A [Vis alle 9 forfattere av denne artikkelen] (2021). Plin2 deletion increases cholesteryl ester lipid droplet content and disturbs cholesterol balance in adrenal cortex. Journal of Lipid Research. ISSN 0022-2275. 62. doi: 10.1016/J.JLR.2021.100048. Fulltekst i vitenarkiv Vis sammendrag

  Cholesteryl esters (CEs) are the water-insoluble transport and storage form of cholesterol. Steroidogenic cells primarily store CEs in cytoplasmic lipid droplet (LD) organelles, as contrasted to the majority of mammalian cell types that predominantly store triacylglycerol (TAG) in LDs. The LD-binding Plin2 binds to both CE- and TAG-rich LDs, and although Plin2 is known to regulate degradation of TAG-rich LDs, its role for regulation of CE-rich LDs is unclear. To investigate the role of Plin2 in the regulation of CE-rich LDs, we performed histological and molecular characterization of adrenal glands from Plin2+/+ and Plin2−/− mice. Adrenal glands of Plin2−/− mice had significantly enlarged organ size, increased size and numbers of CE-rich LDs in cortical cells, elevated cellular unesterified cholesterol levels, and increased expression of macrophage markers and genes facilitating reverse cholesterol transport. Despite altered LD storage, mobilization of adrenal LDs and secretion of corticosterone induced by adrenocorticotropic hormone stimulation or starvation were similar in Plin2+/+ and Plin2−/− mice. Plin2−/− adrenals accumulated ceroid-like structures rich in multilamellar bodies in the adrenal cortex-medulla boundary, which increased with age, particularly in females. Finally, Plin2−/− mice displayed unexpectedly high levels of phosphatidylglycerols, which directly paralleled the accumulation of these ceroid-like structures. Our findings demonstrate an important role of Plin2 for regulation of CE-rich LDs and cellular cholesterol balance in the adrenal cortex.

• Hustad, Kristin Solheim; Ottestad, Inger Olaug; Hjorth, Marit; Dalen, Knut Tomas; Sæther, Thomas & Sheikh, Navida Akhter [Vis alle 9 forfattere av denne artikkelen] (2021). No effect of salmon fish protein on 2-h glucose in adults with increased risk of type 2 diabetes: a randomised controlled trial. British Journal of Nutrition. ISSN 0007-1145. 126(9), s. 1304–1313. doi: 10.1017/S0007114521000040. Fulltekst i vitenarkiv Vis sammendrag

  Abstract The association between fish consumption and decreased risk of CVD is well documented. However, studies on health effects of fish consumption suggest that other components than n -3 PUFA have beneficial cardiometabolic effects, including effects on glucose metabolism. The aim of the present study was to investigate effects of salmon fish protein on cardiometabolic risk markers in a double-blind, randomised controlled parallel trial. We hypothesised that daily intake of a salmon fish protein supplement for 8 weeks would improve glucose tolerance in persons with increased risk of type 2 diabetes mellitus (T2DM). Our primary outcome measure was serum glucose (s-glucose) 2 h after a standardised oral glucose tolerance test. In total, eighty-eight adults with elevated s-glucose levels were randomised to 7·5 g of salmon fish protein/d or placebo, and seventy-four participants were included in the analysis. We found no significant effect of salmon fish protein supplementation on our primary outcome or other markers related to glucose tolerance, serum lipids, weight or blood pressure compared with placebo. The present study does not support the hypothesis that daily intake of a salmon fish protein supplement for 8 weeks improves glucose tolerance in persons with increased risk of T2DM.

• Norheim, Frode Amador; Krishnan, Karthickeyan Chella; Bjellaas, Thomas; Vergnes, Laurent; Pan, Calvin & Parks, Brian W. [Vis alle 18 forfattere av denne artikkelen] (2021). Genetic regulation of liver lipids in a mouse model of insulin resistance and hepatic steatosis. Molecular Systems Biology. 17. doi: 10.15252/msb.20209684. Fulltekst i vitenarkiv Vis sammendrag

  To elucidate the contributions of specific lipid species to metabolic traits, we integrated global hepatic lipid data with other omics measures and genetic data from a cohort of about 100 diverse inbred strains of mice fed a high-fat/high-sucrose diet for 8 weeks. Association mapping, correlation, structure analyses, and network modeling revealed pathways and genes underlying these interactions. In particular, our studies lead to the identification of Ifi203 and Map2k6 as regulators of hepatic phosphatidylcholine homeostasis and triacylglycerol accumulation, respectively. Our analyses highlight mechanisms for how genetic variation in hepatic lipidome can be linked to physiological and molecular phenotypes, such as microbiota composition.

• Li, Yuchuan; Torp, May-Kristin; Norheim, Frode; Khanal, Prabhat; Kimmel, Alan R. & Stensløkken, Kåre-Olav [Vis alle 8 forfattere av denne artikkelen] (2020). Isolated Plin5-deficient cardiomyocytes store less lipid droplets than normal, but without increased sensitivity to hypoxia. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. ISSN 1388-1981. 1866(4). doi: 10.1016/j.bbalip.2020.158873. Fulltekst i vitenarkiv Vis sammendrag

  Plin5 is abundantly expressed in the heart where it binds to lipid droplets (LDs) and facilitates physical interaction between LDs and mitochondria. We isolated cardiomyocytes from adult Plin5+/+ and Plin5-/- mice to study the role of Plin5 for fatty acid uptake, LD accumulation, fatty acid oxidation, and tolerance to hypoxia. Cardiomyocytes isolated from Plin5-/- mice cultured with oleic acid stored less LDs than Plin5+/+, but comparable levels to Plin5+/+ cardiomyocytes when adipose triglyceride lipase activity was inhibited. The ability to oxidize fatty acids into CO2 was similar between Plin5+/+ and Plin5-/- cardiomyocytes, but Plin5-/- cardiomyocytes had a transient increase in intracellular fatty acid oxidation intermediates. After pre-incubation with oleic acids, Plin5-/- cardiomyocytes retained a higher content of glycogen and showed improved tolerance to hypoxia compared to Plin5+/+. In isolated, perfused hearts, deletion of Plin5 had no important effect on ventricular pressures or infarct size after ischemia. Old Plin5-/- mice had reduced levels of cardiac triacylglycerides, increased heart weight, and apart from modest elevated expression of mRNAs for beta myosin heavy chain Myh7 and the fatty acid transporter Cd36, other genes involved in fatty acid oxidation, glycogen metabolism and glucose utilization were essentially unchanged by removal of Plin5. Plin5 seems to facilitate cardiac LD storage primarily by repressing adipose triglyceride lipase activity without altering cardiac fatty acid oxidation capacity. Expression of Plin5 and cardiac LD content of isolated cardiomyocytes has little importance for tolerance to acute hypoxia and ischemia, which contrasts the protective role for Plin5 in mouse models during myocardial ischemia.

• Henjum, Sigrun; Brantsæter, Anne Lise; Holvik, Kristin; Lillegaard, Inger Therese Laugsand; Mangschou, Bente & Parr, Christine Louise [Vis alle 14 forfattere av denne artikkelen] (2020). Benefit and risk assessment of iodization of household salt and salt used in bread and bakery products. Scientific opinion of the Panel on Nutrition, Dietetic Products, Novel Food and Allergy of the Norwegian Scientific Committee for Food and Environment. VKM Report. 2020(5), s. 1–312. Fulltekst i vitenarkiv
• Raheel, Tayyaba Qureshi; Sørensen, Christina; Berghuis, Paul; Jensen, Vidar; Dobszay, Marton B. & Farkas, Tamás [Vis alle 15 forfattere av denne artikkelen] (2019). The glutamine transporter Slc38a1 regulates GABAergic neurotransmission and synaptic plasticity. Cerebral Cortex. ISSN 1047-3211. 29(12), s. 5166–5179. doi: 10.1093/cercor/bhz055. Fulltekst i vitenarkiv Vis sammendrag

  GABA signaling sustains fundamental brain functions, from nervous system development to the synchronization of population activity and synaptic plasticity. Despite these pivotal features, molecular determinants underscoring the rapid and cell-autonomous replenishment of the vesicular neurotransmitter GABA and its impact on synaptic plasticity remain elusive. Here, we show that genetic disruption of the glutamine transporter Slc38a1 in mice hampers GABA synthesis, modifies synaptic vesicle morphology in GABAergic presynapses and impairs critical period plasticity. We demonstrate that Slc38a1-mediated glutamine transport regulates vesicular GABA content, induces high-frequency membrane oscillations and shapes cortical processing and plasticity. Taken together, this work shows that Slc38a1 is not merely a transporter accumulating glutamine for metabolic purposes, but a key component regulating several neuronal functions.

• Mardani, Ismena; Dalen, Knut Tomas; Miljanovic, Azra; Drevinge, Christina; Ståhlman, Marcus & Klevstig, Martina [Vis alle 17 forfattere av denne artikkelen] (2019). Plin2-deficiency reduces lipophagy and results in increased lipid accumulation in the heart. Scientific Reports. 9(1). doi: 10.1038/s41598-019-43335-y. Fulltekst i vitenarkiv Vis sammendrag

  Myocardial dysfunction is commonly associated with accumulation of cardiac lipid droplets (LDs). Perilipin 2 (Plin2) is a LD protein that is involved in LD formation, stability and trafficking events within the cell. Even though Plin2 is highly expressed in the heart, little is known about its role in myocardial lipid storage. A recent report shows that cardiac overexpression of Plin2 result in massive myocardial steatosis suggesting that Plin2 stabilizes LDs. In this study, we hypothesized that deficiency in Plin2 would result in reduced myocardial lipid storage. In contrast to our hypothesis, we found increased accumulation of triglycerides in hearts, and specifically in cardiomyocytes, from Plin2−/− mice. Although Plin2−/− mice had markedly enhanced lipid levels in the heart, they had normal heart function under baseline conditions and under mild stress. However, after an induced myocardial infarction, stroke volume and cardiac output were reduced in Plin2−/− mice compared with Plin2+/+ mice. We further demonstrated that the increased triglyceride accumulation in Plin2-deficient hearts was caused by altered lipophagy. Together, our data show that Plin2 is important for proper hydrolysis of LDs.

• Gamage, Thilini Hansamali Gamage Yaddehi; Gunnes, Gjermund; Lee, Robert Hugh; Louch, William Edward; Holmgren, Asbjørn & Bruton, Joseph D. [Vis alle 19 forfattere av denne artikkelen] (2018). STIM1 R304W causes muscle degeneration and impaired platelet activation in mice. Cell Calcium. ISSN 0143-4160. 76, s. 87–100. doi: 10.1016/j.ceca.2018.10.001. Fulltekst i vitenarkiv Vis sammendrag

  STIM1 and ORAI1 regulate store-operated Ca2+ entry (SOCE) in most cell types, and mutations in these proteins have deleterious and diverse effects. We established a mouse line expressing the STIM1 R304 W gain-of-function mutation causing Stormorken syndrome to explore effects on organ and cell physiology. While STIM1 R304 W was lethal in the homozygous state, surviving mice presented with reduced growth, skeletal muscle degeneration, and reduced exercise endurance. Variable STIM1 expression levels between tissues directly impacted cellular SOCE capacity. In contrast to patients with Stormorken syndrome, STIM1 was downregulated in fibroblasts from Stim1R304W/R304W mice, which maintained SOCE despite constitutive protein activity. In studies using foetal liver chimeras, STIM1 protein was undetectable in homozygous megakaryocytes and platelets, resulting in impaired platelet activation and absent SOCE. These data indicate that downregulation of STIM1 R304 W effectively opposes the gain-of-function phenotype associated with this mutation, and highlight the importance of STIM1 in skeletal muscle development and integrity.

• Lee, Yun K.; Sohn, Jee Hyung; Han, Ji Seul; Park, Yoon Jeong; Jeon, Yong Geun & Ji, Yul [Vis alle 10 forfattere av denne artikkelen] (2018). Perilipin 3 deficiency stimulates thermogenic Beige adipocytes through PPARa activation. Diabetes. ISSN 0012-1797. 67(5), s. 791–804. doi: 10.2337/db17-0983. Fulltekst i vitenarkiv
• Fan, Qiong; Nørgaard, Rikke Christine; Bindesbøll, Christian; Lucas, Christin; Dalen, Knut Tomas & Babaie, Eshrat [Vis alle 10 forfattere av denne artikkelen] (2017). LXR? regulates hepatic ChREBP? activity and lipogenesis upon glucose, but not fructose feeding in mice. Nutrients. 9(7). doi: 10.3390/nu9070678. Fulltekst i vitenarkiv
• Yasein, Nadia Haj; Berg, Ole; Jerneren, Fredrik; Refsum, Helga; Nebb, Hilde Irene & Dalen, Knut Tomas (2017). Cysteine deprivation prevents induction of peroxisome proliferator-activated receptor gamma-2 and adipose differentiation of 3T3-L1 cells. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. ISSN 1388-1981. 1862(6), s. 623–635. doi: 10.1016/j.bbalip.2017.02.009. Fulltekst i vitenarkiv
• Feng, Yuan Zeng; Lund, Jenny; Li, Yuchuan; Knabenes, Irlin; Bakke, Siril Skaret & Kase, Eili Tranheim [Vis alle 11 forfattere av denne artikkelen] (2017). Loss of perilipin 2 in cultured myotubes enhances lipolysis and redirects the metabolic energy balance from glucose oxidation towards fatty acid oxidation. Journal of Lipid Research. ISSN 0022-2275. 58(11), s. 2147–2161. doi: 10.1194/jlr.M079764. Fulltekst i vitenarkiv Vis sammendrag

  Lipid droplet (LD) coating proteins are essential for the formation and stability of intracellular LDs. Plin2 is an abundant LD coating protein in skeletal muscle, but its importance for muscle function is unclear. We show that myotubes established from Plin2−/− mice contain reduced content of LDs and accumulate less oleic acid (OA) in triacylglycerol (TAG) due to elevated LD hydrolysis in comparison with Plin2+/+ myotubes. The reduced ability to store TAG in LDs in Plin2−/− myotubes is accompanied by a shift in energy metabolism. Plin2−/− myotubes are characterized by increased oxidation of OA, lower glycogen synthesis, and reduced glucose oxidation in comparison with Plin2+/+ myotubes, perhaps reflecting competition between FAs and glucose as part of the Randle cycle. In accord with these metabolic changes, Plin2−/− myotubes have elevated expression of Ppara and Ppargc1a, transcription factors that stimulate expression of genes important for FA oxidation, whereas genes involved in glucose uptake and oxidation are suppressed. Loss of Plin2 had no impact on insulin-stimulated Akt phosphorylation. Our results suggest that Plin2 is essential for protecting the pool of skeletal muscle LDs to avoid an uncontrolled hydrolysis of stored TAG and to balance skeletal muscle energy metabolism. This article was originally published in the Journal of Lipid Research. © 2017 American Society for Biochemistry and Molecular Biology

• Andersson, Linda; Drevinge, Christina; Mardani, Ismena; Dalen, Knut Tomas; Ståhlman, Marcus & Klevstig, Martina [Vis alle 18 forfattere av denne artikkelen] (2017). Deficiency in perilipin 5 reduces mitochondrial function and membrane depolarization in mouse hearts. International Journal of Biochemistry and Cell Biology. ISSN 1357-2725. 91, s. 9–13. doi: 10.1016/j.biocel.2017.07.021. Fulltekst i vitenarkiv
• Drevinge, Christina; Dalen, Knut Tomas; Mannila, Maria Nastase; Täng, Margareta Scharin; Ståhlman, Marcus & Klevstig, Martina [Vis alle 30 forfattere av denne artikkelen] (2016). Perilipin 5 is protective in the ischemic heart. International Journal of Cardiology. ISSN 0167-5273. 219, s. 446–454. doi: 10.1016/j.ijcard.2016.06.037. Fulltekst i vitenarkiv
• Dahl, John Arne; Jung, Inkyung; Aanes, Håvard; Greggains, Gareth; Manaf, Adeel & Lerdrup, Mads [Vis alle 20 forfattere av denne artikkelen] (2016). Broad histone H3K4me3 domains in mouse oocytes modulate maternal-to-zygotic transition. Nature. ISSN 0028-0836. 537(7621), s. 548–552. doi: 10.1038/nature19360. Fulltekst i vitenarkiv
• Pourteymour, Shirin; Lee, Sindre; Langleite, Torgrim Mikal; Eckardt, Kristin; Hjorth, Marit & Bindesbøll, Christian [Vis alle 11 forfattere av denne artikkelen] (2015). Perilipin 4 in human skeletal muscle: localization and effect of physical activity. Physiological Reports. 3:e12481(8), s. 1–15. doi: 10.14814/phy2.12481. Fulltekst i vitenarkiv
• Norheim, Frode; Hjorth, Marit; Langleite, Torgrim Mikal; Lee, Sindre; Holen, Torgeir & Bindesbøll, Christian [Vis alle 13 forfattere av denne artikkelen] (2014). Regulation of angiopoietin-like protein 4 Production during and after exercise. Physiological Reports. 2(8), s. 12–12. doi: 10.14814/phy2.12109. Fulltekst i vitenarkiv
• Bindesbøll, Christian; Berg, Ole; Arntsen, Borghild M; Nebb, Hilde Irene & Dalen, Knut Tomas (2013). Fatty acids regulate perilipin5 in muscle by activating PPARdelta. Journal of Lipid Research. ISSN 0022-2275. 54(7), s. 1949–1963. doi: 10.1194/jlr.M038992. Fulltekst i vitenarkiv
• Haj-Yasein, Nadia Nabil; Dalen, Knut Tomas; Berg, Ole; Bastani, Nasser Ezzatkhah; Refsum, Helga & Nebb, Hilde Irene (2013). Low Cysteine Interferes With PPARγ Activity And Reduces Adipocyte Differentiation. The Journal of Inherited Metabolic Disease (JIMD). ISSN 0141-8955. 36, s. S44–S44. doi: 10.1007/s10545-013-9631-1. Fulltekst i vitenarkiv
• Telle, Vibeke Helen; Halvorsen, Bente; Dalen, Knut Tomas; Narverud, Ingunn; Rao, Nima & Granlund, L [Vis alle 8 forfattere av denne artikkelen] (2013). Altered expression of genes involved in lipid metabolism in obese subjects with unfavourable phenotype. Genes & Nutrition. ISSN 1555-8932. 8(4), s. 425–434. doi: 10.1007/s12263-012-0329-z. Fulltekst i vitenarkiv
• Norheim, Frode; Gjelstad, Ingrid Merethe Fange; Hjorth, Marit; Vinknes, Kathrine; Langleite, Torgrim Mikal & Holen, Torgeir [Vis alle 12 forfattere av denne artikkelen] (2012). Molecular nutrition research - the modern way of performing nutritional science. Nutrients. 4(12), s. 1898–1944. doi: 10.3390/nu4121898. Fulltekst i vitenarkiv Vis sammendrag

  In spite of amazing progress in food supply and nutritional science, and a striking increase in life expectancy of approximately 2.5 months per year in many countries during the previous 150 years, modern nutritional research has a great potential of still contributing to improved health for future generations, granted that the revolutions in molecular and systems technologies are applied to nutritional questions. Descriptive and mechanistic studies using state of the art epidemiology, food intake registration, genomics with single nucleotide polymorphisms (SNPs) and epigenomics, transcriptomics, proteomics, metabolomics, advanced biostatistics, imaging, calorimetry, cell biology, challenge tests (meals, exercise, etc.), and integration of all data by systems biology, will provide insight on a much higher level than today in a field we may name molecular nutrition research. To take advantage of all the new technologies scientists should develop international collaboration and gather data in large open access databases like the suggested Nutritional Phenotype database (dbNP). This collaboration will promote standardization of procedures (SOP), and provide a possibility to use collected data in future research projects. The ultimate goals of future nutritional research are to understand the detailed mechanisms of action for how nutrients/foods interact with the body and thereby enhance health and treat diet-related diseases.

• Hsieh, Kai; Lee, Yen-Kun; Londos, C; Raaka, BM; Dalen, Knut Tomas & kimmel, Alan (2012). Perilipin family members preferentially sequester to either triacylglycerol-specific or cholesteryl-ester-specific intracellular lipid storage droplets. Journal of Cell Science. ISSN 0021-9533. 125(17), s. 4067–4076. doi: 10.1242/jcs.104943. Fulltekst i vitenarkiv
• Wang, H; Bell, H; Sreenevasan, u; Hu, H; Liu, J & Dalen, Knut Tomas [Vis alle 13 forfattere av denne artikkelen] (2011). Unique regulation of adipose triglyceride lipase (ATGL) by perilipin 5, a lipid droplet-associated protein. Journal of Biological Chemistry. ISSN 0021-9258. 286(6), s. 15707–15715. Fulltekst i vitenarkiv
• Weedon, Mina Susanne; Dalen, Knut Tomas; Solaas, Karianne; Staff, Anne Cathrine; Duttaroy, Asim K. & Nebb, Hilde Irene (2010). Activation of LXR increases acyl-CoA synthetase activity through direct regulation of ACSL3 in human placental trophoblast cells. Journal of Lipid Research. ISSN 0022-2275. 51(7), s. 1886–1896. doi: 10.1194/jlr.M004978. Fulltekst i vitenarkiv
• Qin, Yan; Dalen, Knut Tomas; Gustafsson, Jan Åke & Nebb, Hilde Irene (2009). Regulation of hepatic fatty acid elongase 5 by LXRalpha-SREBP-1c. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. ISSN 1388-1981. 1791(2), s. 140–147. doi: 10.1016/j.bbalip.2008.12.003. Fulltekst i vitenarkiv
• Wang, H; hu, l; Dalen, Knut Tomas; dorward, h; Marcinkiewicz, a & Russell, d [Vis alle 13 forfattere av denne artikkelen] (2009). Activation of hormone-sensitive lipase requires two steps, protein phosphorylation and binding to the PAT-1 domain of lipid droplet coat proteins. Journal of Biological Chemistry. ISSN 0021-9258. 46(284), s. 32116–32125. Fulltekst i vitenarkiv
• Dalen, Knut Tomas; Dahl, Tuva Børresdatter; Holter, Elin; Arntsen, Borghild M; Londos, C & Sztalryd, C [Vis alle 7 forfattere av denne artikkelen] (2007). LSDP5 is a PAT protein specifically expressed in fatty acid oxidizing tissues. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. ISSN 1388-1981. 1771, s. 210–227. doi: 10.1016/j.bbalip.2006.11.011. Fulltekst i vitenarkiv
• Tobin, Kari Anne Risan; Harsem, NK; Dalen, Knut Tomas; Staff, AC; Nebb, Hilde Irene & Duttaroy, Asim K. (2006). Regulation of ADRP expression by long-chain polyunsaturated fatty acids in BeWo cells, a human placental choriocarcinoma cell line. Journal of Lipid Research. ISSN 0022-2275. 47, s. 815–823. Fulltekst i vitenarkiv
• Wang, Line M. Grønning; Tingsabadh, R; Hardy, K; Dalen, Knut Tomas; Jat, PS & Gnudi, L [Vis alle 7 forfattere av denne artikkelen] (2006). Glucose induces increases in levels of the transcriptional repressor Id2 via the hexosamine pathway. American Journal of Physiology. Endocrinology and Metabolism. ISSN 0193-1849. 290(4), s. 599–606. Fulltekst i vitenarkiv
• Dalen, Knut Tomas; Ulven, Stine Marie; Arntsen, Borghild M; Solaas, Karianne & Nebb, Hilde Irene (2006). PPAR alpha activators and fasting induce the expression of adipose differentiation-related protein in liver. Journal of Lipid Research. ISSN 0022-2275. 47, s. 931–943. Fulltekst i vitenarkiv
• Zernichow, L; Dalen, Knut Tomas; Dalen, L.; Prydz, K; Winberg, Jan-Olof & Kolset, S O (2006). Secretion of proteases in serglycin transfected Madin-Darby canine kidney cells. The FEBS Journal. ISSN 1742-464X. 273. Fulltekst i vitenarkiv
• Ulven, Stine Marie; Dalen, Knut Tomas; Gustafsson, JA & Nebb, Hilde Irene (2005). LXR is crucial in lipid metabolism. Prostaglandins, Leukotrienes and Essential Fatty Acids. ISSN 0952-3278. 73, s. 59–63. Fulltekst i vitenarkiv

Se alle arbeider i NVA

• Jez, Joseph & Dalen, Knut Tomas (2021). Encyclopedia of Biological Chemistry III (Third Edition). Elsevier. ISBN 9780128220405. 500 s. Fulltekst i vitenarkiv
• Dalen, Knut Tomas; londos, constantine & kimmel, Alan (2011). Adipocyte Fat Mobilization: The Regulatory Roles of Perilipin 1, Adipose Triglyceride Lipase, and Hormone Sensitive Lipase. Elsevier. ISBN 9780124437104. Fulltekst i vitenarkiv

Se alle arbeider i NVA

• Andersen, Lene Frost; Lillegaard, Inger Therese L.; Mangschou, Bente; Medin, Anine; Aakre, Inger & Dalen, Knut Tomas [Vis alle 12 forfattere av denne artikkelen] (2026). Vurdering av inntaket av vitaminer og mineraler i Norge sammenlignet med inntaksdata fra EFSA. VKM Bulletin. 2026(1), s. 1–65. Fulltekst i vitenarkiv Vis sammendrag

  Vitenskapskomiteen for mat og miljø (VKM) har undersøkt hvordan nordmenns inntak av vitaminer og mineraler skiller seg fra resten av Europa. Vi konkluderer med at det er viktig å ta høyde for norske data når man fastsetter nye maksimumsgrenser.

• Bodin, Johanna Eva; Blaalid, Rakel; Duale, Nur; Tekle, Selamawit; Nielsen, Kaare Magne & Olsen, Siri Lie [Vis alle 11 forfattere av denne artikkelen] (2025). Environmental risk assessment of genetically modified late blight resistant potato for use in field trials in Norway. VKM Bulletin. 2025(28), s. 1–39. doi: https:/vkm.no/english/riskassessments/allpublications/nohazardsidentifiedinafieldtrialwithlateblightresistantpotato.4.26217ad5192ae2cc0cc94d7.html. Fulltekst i vitenarkiv Vis sammendrag

  Upon a request from The Norwegian Environment Agency, VKM has assessed potential risks to the environment from genetically modified (GM) late blight resistant potato intended for cultivation in small scale field trials (100 m2) over several seasons in Norway. Late blight is the most severe disease affecting potato and tomato plants in Norway, and is caused by the pathogen Phytophthora infestans, a fungus-like microorganism. Increased resistance of the GM potato to the pathogen is enabled by expression of three genes acquired from wild potato relatives (Solanum spp.). The GM potato is also made resistant to a potato virus (PVY), as well as certain herbicides that were used for selection purposes during plant development. The application is presented by the Norwegian Institute of Bioeconomy Research (NIBIO) and covers two GM potato breeding lines (SLJ25587_11 and SLJ25587_49) developed by the Sainsbury Laboratory, Norwich, England. The lines were generated from two independent T-DNA transformation events using an Agrobacterium-mediated transfer technique. VKM has assessed risks to the environment, including any effects on human and/or animal health, which may arise from the field trial. The environmental risk assessment (ERA) was structured according to EFSA guidance and included molecular characterisation of the GM potato, effects on the environment, and non-food/feed effects on human and animal health. The specific areas of concern included spread and survival of the GM potato outside of the field area, plant-to-plant gene flow, plant-to-microorganism gene flow, effects on specific potato pathogen target organisms (Phytophthora infestans and PVY), and effects on non-target organisms. The assessment also included an evaluation of the risk-reducing measures proposed in the application. VKM concludes that the applicant’s documentation on molecular characterisation is sufficient to demonstrate the presence of the intended target genes (T-DNA) as well as the absence of vector backbone elements in the two GM potato lines intended for use in the field trials. The insertion sites in the plant genome have not been described, but this is not considered critical for the evaluation of the planned field trial. Available scientific literature suggests that cultivated potato is a biologically contained species in Norway with the following characteristics: plants do not persist or invade natural habitats and have limited capacity of vertical gene transfer including outcrossing with cultivated or wild Solanum species. The likelihood of persistence and gene transfer from the GM potato is hence also considered very low as the introduced traits are not considered to affect these characteristics. A specific hazard has not been identified for these characteristics in relation to the GM potato. VKM therefore concludes that the risk of adverse effects from persistence or plant-to-plant gene transfer from the GM potatoes is low. VKM has not identified specific hazards from horizontal transfer of the inserted genes in the GM potatoes to microorganisms, and as these are derived from Solanum spp., microorganisms in the field area might already be naturally exposed to similar genes from local flora. Horizontal gene transfer is also considered very unlikely given that the T-DNA consists of plant derived genes with plant promoters. VKM therefore concludes that the risk of adverse effects from horizontal gene transfer from the GM potatoes is low. No indications of an increase in toxicity or allergenic potential of the GM potatoes have been identified compared to conventional non-GM potatoes. The target organisms are sufficiently defined, and potential adverse effects on non-target organisms are not expected from the novel traits expressed by the GM potato. As a specific hazard with a defined likelihood has not been identified, VKM concludes there is a low risk of adverse effects from these areas of concern. VKM concludes that the management proposed for the field trial is sufficient to contain the GM plants within the trial site for the duration of the experiment, which may include repeated planting over several seasons, and that the proposed measures for monitoring, removing, and disposal of GM material, as well as the follow up period of the site, is adequate. The limited field trial area, with a maximum of 200 plants/year, limited invasive and hybridizing potential of potatoes, and low survivability beyond a growing season, further mitigates potential risks.

• Andersen, Lene Frost; Lillegaard, Inger Therese Laugsand; Mangschou, Bente; Medin, Anine Christine; Aakre, Inger & Dalen, Knut Tomas [Vis alle 12 forfattere av denne artikkelen] (2025). New update of a fortification model. VKM Bulletin. VKM Bulletin 2025: 13(Bulletin 2025: 13), s. 1–34. Fulltekst i vitenarkiv Vis sammendrag

  VKM has calculated the intakes of vitamins and minerals and compared them with the tolerable upper intake levels (UL) in a model for assessing the fortification of food and drink. Fortification means adding vitamins and minerals. The intake calculations cover all age groups. The model has been updated with data from a new dietary survey for adults, and with new tolerable upper intake levels from EFSA for several of the vitamins and minerals. Some of the data entered into the model has been taken from Danish dietary surveys, as there is no Norwegian data available. For most nutrients, it is the amount that can be added for 1- and 2-year-olds that regulates the fortification. The model was established in 2006, and has been updated in 2009, 2013 and 2021. The model does not include the risk of low intake of nutrients. The work has been commissioned by the Norwegian Food Safety Authority, which will use the results from the model as part of the basis for assessing applications for food fortification.

• Schultz, Gry Irene Granli; Parr, Christine Louise; Trosvik, Pål; Yazdankhah, Siamak Pour; Andersen, Lene Frost & Dalen, Knut Tomas [Vis alle 14 forfattere av denne artikkelen] (2025). Health risk assessment of Bifidobacterium breve M-16V in infant formula. VKM Bulletin. 2025(VKM Bulletin 2025: 09), s. 1–115. Fulltekst i vitenarkiv Vis sammendrag

  VKM has not identified any short-term negative health effects from consuming infant formula with Bifidobacterium breve M-16V. However, there is uncertainty and limited research on possible long-term effects. There is also little research conducted independently of the manufacturers. The Norwegian Food Safety Authority has asked VKM to assess whether there may be health risks associated with giving infants (up to 12 months) infant formula supplemented with a specific probiotic bacterium (Bifidobacterium breve M-16V). "Probiotics" generally refers to health products containing live microorganisms, usually bacteria. Currently, some infant formulas outside Norway are supplemented with freeze-dried probiotic bacteria. The bacterium Bifidobacterium breve M-16V (B. breve M-16V) in given concentrations is considered safe in the USA and EU for use in food, but this status is regularly reviewed in the EU and may change if negative health effects are discovered. In infants, the intestinal microbiota (composition of microorganisms) and immune system are not fully developed, and it is uncertain whether the addition of high doses of probiotic bacteria during infancy may have unintended long-term effects. Background for the risk assessment A company has applied to the Norwegian Food Safety Authority to market two specific infant formulas in Norway: one peptide-based and another amino acid-based. The products are intended for infants having allergies and are regulated as foods for special medical purposes. Both products are supplemented with the probiotic bacterium B. breve M-16V. The Norwegian Food Safety Authority has asked VKM to assess whether there may be health risks associated with giving infants these products specifically, and infant formula supplemented with B. breve M-16V in general. VKM’s methodology A multidisciplinary project group appointed by VKM has reviewed documentation from the company. The group has also conducted a systematic literature review of health effects reported in studies where infants received infant formula supplemented with B. breve M-16V and calculated the possible intake of infant formula and B. breve M-16V among Norwegian infants. VKM has only assessed the risk of negative health effects based on the assignment and according to guidelines for probiotics in food, not as a medicinal product. The assessment has been approved by a multidisciplinary approval group, also appointed by VKM. Findings VKM has not found any unwanted properties of B. breve M-16V based on reported laboratory studies and animal experiments. VKM has also not found negative health effects in 13 clinical studies involving a total of 1580 children, of whom 836 received infant formula supplemented with B. breve M-16V (test) and the rest received infant formula without B. breve M-16V (control). The studies lasted from 6 weeks to 12 months (median 16 weeks). VKM found no consistent differences between test and control groups in reported side effects, children's growth, or symptoms from the gastrointestinal tract, skin, or respiratory system as long as the studies were ongoing (short-term). VKM has found only two studies of long-term effects in children one year (development of asthma symptoms) or 3-5 years (neurocognitive outcomes) after they received infant formula with B. breve M-16V. This is too little to draw conclusions about long-term effects.

• Steffensen, Inger-Lise Karin; Bodin, Johanna Eva; Dalen, Knut Tomas; Mangschou, Bente; Aakre, Inger & Andersen, Lene Frost [Vis alle 13 forfattere av denne artikkelen] (2024). Risk assessment of quercetin dihydrate and rutin in food supplements – “Other substances”. VKM Bulletin. 2024(9), s. 1–149. Fulltekst i vitenarkiv Vis sammendrag

  Det er trygt å bruke flavonoidene quercetin eller rutin i bestemte i kosttilskudd, ifølge Vitenskapskomiteen for mat og miljø (VKM). Det er hovedbudskapet i en risikovurdering utført på oppdrag fra Mattilsynet. I rapporten ble det konkludert at det er trygt å bruke quercetin eller rutin i kosttilskudd i daglige doser på 5 mg rutin for barn fra fireårsalderen, daglige doser på 25 mg rutin for voksne og 500 mg quercetin dihydrat for voksne i hvert fall opp til tre måneder. VKM har vurdert risiko for helseskadelige effekter ved daglig inntak av kosttilskudd med 25 mg rutin eller 500 mg quercetin dihydrat for voksne fra 18 år og eldre, og 5 mg rutin for barn fra fireårsalderen. Quercetin og rutin er flavonoider. Disse finnes naturlig i planter og inngår i kosten, særlig i frukt, grønnsaker og te. Mange flavonoider fra mat og drikke tas i liten grad opp i kroppen. Risikovurderingen er basert på informasjon fra en systematisk kunnskapsoppsummering av 23 randomiserte kontrollerte studier (studier hvor man undersøker effekten av en behandling ved å fordele deltagere tilfeldig i behandlings- og kontrollgruppe(r). Disse studiene omfattet voksne mennesker. I tillegg er det brukt kunnskap om hvordan stoffene håndteres i kroppen og noen dyrestudier i vurderingen. Studiene hadde undersøkt, men funnet få, og lite alvorlige, skadelige helseeffekter. Den lengste studien varte i 10 måneder. Konklusjonen for barna er basert på studiene av voksne og én studie spesifikk av barn. På grunn av mangel på tilstrekkelige data om gravide kvinner og fostre, og mangel på data om ammende kvinner og deres spedbarn, samt om barn generelt, er det ikke kjent om disse gruppene potensielt kan være mer sårbare for disse stoffene enn voksne. Studiene i mennesker undersøkte hovedsakelig positive effekter av quercetin og rutin for en rekke ulike tilstander og sykdommer. Mulige helseskadelige effekter ble dokumentert og undersøkt i varierende grad, og svært få og lite alvorlige skadelige effekter ble observert. Resultatene understøttes også av dyrestudiene. Ettersom de fleste studiene med quercetin og rutin ikke undersøkte bruk av stoffene i mer enn tre måneder, er lengre tids inntak mer usikkert, selv om noen få studier heller ikke fant skadelige effekter etter bruk i seks til ti måneder, sier Inger-Lise Steffensen, faglig leder av arbeidet. VKM har ikke beregnet bidrag fra andre kilder til rutin eller quercetin som mat, og har heller ikke vurdert bruk av stoffene til behandling av ulike tilstander og sykdommer. Noe data kan tyde på at personer med kronisk nyresykdom eller østrogen-avhengig kreft kanskje kan være sårbare for skadelige effekter av quercetin. Studier i mennesker og dyr har vist at quercetin kan påvirke opptaket av ulike medikamenter i kroppen, og kan påvirke enzymer som omdanner medikamenter. Om quercetin og rutin Quercetin og rutin inngår i gruppen “andre stoffer”. Dette er stoffer med ernæringsmessig eller fysiologisk effekt, og som ikke er vitaminer eller mineraler. Risikovurderingen er godkjent av VKMs faggruppe for ernæring, dietetiske produkter, ny mat og allergi.

• Doncheva, Atanaska Ivanova; Li, Yuchuan; Khanal, Prabhat & Dalen, Knut Tomas (2022). Perilipin 2 regulates hepatic lipid content and lipid droplet size during fasting. Fulltekst i vitenarkiv
• Dalen, Knut Tomas (2022). Perilipins and regulation of intracellular lipid droplets. Fulltekst i vitenarkiv
• Hjorth, Marit; Doncheva, Atanaska Ivanova; Norheim, Frode Amador; Ulven, Stine Marie; Holven, Kirsten Bjørklund & Sæther, Thomas [Vis alle 7 forfattere av denne artikkelen] (2022). Consumption of salmon fishmeal increases hepatic cholesterol content in obese C57BL/6J mice. Fulltekst i vitenarkiv
• Dalen, Knut Tomas (2021). Lipid droplets and transgenic animals. Fulltekst i vitenarkiv
• Dalen, Knut Tomas & Kimmel, Alan R (2021). Lipids | Adipocyte Fat Mobilization: Regulatory Functions Involving Perilipin 1, Adipose Triglyceride Lipase, and Hormone-Sensitive Lipase, Encyclopedia of Biological Chemistry III (Third Edition). Elsevier. ISSN 9780128220405. s. 492–500. doi: 10.1016/B978-0-12-819460-7.00337-6. Fulltekst i vitenarkiv
• Holven, Kirsten Bjørklund; Sæther, Thomas; Hjorth, Marit; Dalen, Knut Tomas; Ulven, Stine Marie & Ottestad, Inger [Vis alle 7 forfattere av denne artikkelen] (2019). Kan fisk utnyttes enda mer og samtidig fremme folkehelsen? Norsk tidsskrift for ernæring (NTFE). ISSN 1503-5034. 17(2), s. 20–22. Fulltekst i vitenarkiv
• Catterall, Tara Cherie; Johnson, Inna; Khan, Shaista; Jermstad, Ingunn; Nesse, Gaute & Klungland, Arne [Vis alle 7 forfattere av denne artikkelen] (2015). The Norwegian Transgenic Centre. Fulltekst i vitenarkiv
• Feng, Yuan Zeng; knabenes, Irlin Knivsland; Bakke, Siril S.; Lund, Jenny; Lee, Y.K. & kimmel, Alan [Vis alle 9 forfattere av denne artikkelen] (2015). Increased lipid oxidation and decreased lipid storage in myotubes lacking the lipid droplet binding protein perilipin2. Fulltekst i vitenarkiv
• Feng, Yuan Zeng; knabenes, Irlin Knivsland; Lund, Jenny; Lee, Y.K.; kimmel, Alan & Thoresen, G. Hege [Vis alle 8 forfattere av denne artikkelen] (2014). Increased lipid oxidation and decreased lipid storage in myotubes lacking perilipin2. Fulltekst i vitenarkiv
• Dalen, Knut Tomas; Haj-Yasein, Nadia Nabil; Berg, Ole; Refsum, Helga & Nebb, Hilde Irene (2014). Cysteine and adipocyte differentiation. Fulltekst i vitenarkiv
• Dalen, Knut Tomas (2014). Transgenic techniques provided by the Norwegian Transgenic Centre. Fulltekst i vitenarkiv
• Khan, Shaista; Jermstad, Ingunn; Catterall, Tara Cherie; Nesse, Gaute; Klungland, Arne & Dalen, Knut Tomas (2014). The Norwegian Transgenic Centre. Fulltekst i vitenarkiv
• Bindesbøll, Christian; Berg, Ole; Arntsen, Borghild M; Nebb, Hilde Irene & Dalen, Knut Tomas (2014). Fatty acids regulate perilipin5 in muscle by activating PPARdelta. Fulltekst i vitenarkiv
• Bindesbøll, Christian; Fan, Qiong; Sæther, Thomas; Dalen, Knut Tomas; Nebb, Hilde Irene & Grønning-Wang, Line Mariann (2013). Nuclear receptors as targets for treatment and prevention of metabolic diseases. Fulltekst i vitenarkiv Vis sammendrag

  Obesity, type 2 diabetes (T2D) and its associated comorbidity atherosclerosis are the leading cause of mortality in the Western world. A major consequence of obesity is insulin resistance, which is strongly associated with deposition of fat and uncontrolled glucose production in the liver, thereby contributing to the development of T2D. Peroxisome proliferator-activated receptors (PPARs) and liver X receptors (LXRs) are lipid-activated nuclear receptors (NRs) that through target gene activation regulate systemic glucose and lipid metabolism, control cholesterol transport, and modulate inflammation within the vascular wall. The NR Group at the Department of Nutrition, UoO studies the LXRs and PPARs in cross-talk with signaling pathways activated by lipids, insulin and glucose. We have recently shown that LXRalpha and LXRbeta are targets for glucose-hexosamine-derived OGlcNAc modification in liver and macrophages. Importantly, induction of LXRa O-GlcNAcylation by high carbohydrate feeding coincides with increased expression of the lipogenic gene SREBP-1c. This intriguing observation gives insight into novel aspects of LXR activation, and suggests LXR to be an important mediator of sugar-induced hepatic fat deposition and insulin resistance. Our ultimate goal is to gain new understanding of the role of LXRs and PPARs in the development of diet-induced metabolic diseases and to identify and develop specific ligands from marine microalgae for the treatment of metabolic disease.

• Telle-Hansen, Vibeke; Halvorsen, Bente; Dalen, Knut Tomas; Narverud, Ingunn; Wesseltoft-Rao, Nima & Granlund, Linda [Vis alle 8 forfattere av denne artikkelen] (2013). Altered expression of genes involved in lipid metabolism in obese subjects with unfavourable phenotype. Fulltekst i vitenarkiv
• Dalen, Knut Tomas (2011). Lipid droplet binding proteins and lipid accumulation. Fulltekst i vitenarkiv
• Dalen, Knut Tomas; Londos, C & Nebb, Hilde Irene (2009). PAT proteins and their function on intracellular lipid droplets. Fulltekst i vitenarkiv
• Mikkelsen, Johanne Kristofina; Dalen, Knut Tomas & Hjorth, Marit (2025). Investigating the Role of Perilipin 2 in Atherosclerosis. Universitetet i Oslo. Fulltekst i vitenarkiv Vis sammendrag

  Introduction: Cardiovascular disease (CVD) remains the leading cause of death globally, with atherosclerosis as its primary driver. Atherosclerosis is a chronic inflammatory disease characterised by lipoprotein retention in the arterial wall, macrophage infiltration, and lesion formation. Lipid droplets (LDs) in foam cells store neutral lipids such as triacylglycerol (TAG) and cholesteryl esters (CEs), regulated by LD-associated proteins, including the perilipin (Plin) family. Although Plin2 is highly expressed in macrophages, its role in atherosclerosis is unclear. Materials and methods: To investigate the role of Plin2 in atherosclerosis, male Plin2+/+ and Plin2-/- C57BL/6N mice were injected at 13 weeks of age with an adeno-associated virus serotype 8 (AAV8) carrying a D377Y-mutant murine pro-protein convertase subtilisin/kexin type 9 (Pcsk9) or left uninjected. All mice were subsequently fed an atherogenic diet high in fat, cholesterol, and sucrose. Validation of the AAV model was performed by RT-qPCR, immunoblotting, and measurements of circulating levels of TAG and cholesterol. Body composition, body and organ weights, and hepatic lipid levels were measured. Atherosclerotic lesions in the aortic arch were quantified by lipid staining and image analysis. Bone marrow-derived macrophages (BMDMs) were treated in vitro with cholesterol and oleic acid (OA) and analysed for LD accumulation and gene expression. Results: The AAV8-mPcsk9-D377Y model successfully induced hyperlipidaemia, marked by elevated levels of plasma TAG and cholesterol, due to increased hepatic Pcsk9 mRNA expression and reduced Ldlr protein expression. Plin2 deletion did not affect atherosclerotic lesion size but was associated with reduced body weight and fat mass, and reduced lipid accumulation in liver and plasma. Plin2-deficient BMDMs appeared to accumulate fewer LDs, without any major effects on the expression of genes related to lipid metabolism, inflammation, or immune responses. Conclusion: The findings in this study confirm and highlight a role for Plin2 in systemic and hepatic lipid regulation. Although Plin2 deletion did not reduce atherosclerotic lesions under the tested conditions, its effects on lipid accumulation in liver, plasma, and macrophages warrant further research to investigate its role as a potential therapeutic target in atherosclerosis.

• Løvik, Martinus; Dahl, Lisbeth; Mangschou, Bente; Ulven, Stine Marie; Andersen, Lene Frost & Dalen, Knut Tomas [Vis alle 10 forfattere av denne artikkelen] (2019). Assessment of dietary intake of fluoride and maximum limits of fluoride in food supplements. Opinion of the Panel on Nutrition, Dietetic Products, Novel Food and Allergy of the Norwegian Scientific Committee for Food and Environment. Norwegian Scientific Committee for Food and Environment (VKM). ISSN 9788282593281. Fulltekst i vitenarkiv Vis sammendrag

  The Norwegian Scientific Committee for Food and Environment (Vitenskapskomiteen for mat og miljø, VKM) has, at the request of the Norwegian Food Safety Authority (Mattilsynet, NFSA), evaluated the intake of fluoride in the diet, together with intake of fluoride from dental hygiene and caries prevention products. VKM has also evaluated suggested maximum limits for fluoride in food supplements at 0.5, 1, 5 and 7 mg/day in relation to established tolerable upper intake levels (ULs). The former maximum limit for fluoride of 0.5 mg/day in food supplements was repealed 30 May 2017. Fluorine is a gaseous halogen which occurs naturally only in anionic form as fluoride (F-). Fluorides are ubiquitous in air, water and the lithosphere. Fluoride is found naturally in all water sources. The highest levels are found in groundwater. Surface water usually has lower concentrations of fluoride than groundwater, most often under 0.5 mg/L. Major dietary fluoride sources are water and tea. An important non-dietary source is dental hygiene products such as toothpaste and tablets for caries prevention. There is no fluoridation of drinking water or salt in Norway. Fluoride is not an essential nutrient. Caries is not a fluoride deficiency disease. However, because of the beneficial effects for caries prevention, an adequate intake (AI) of 0.05 mg per kg body weight per day has been set for fluoride by the European Food Safety Authority (EFSA). Readily soluble fluorides (sodium- and potassium fluoride) are rapidly and almost completely absorbed by passive diffusion in the stomach and the small intestine. Absorption is influenced by acidity and concomitant food intake. Absorbed fluoride is rapidly distributed in blood plasma, but is retained only in calcified tissues, that are bones and teeth. Consequently, 99% of the total fluoride content of the body is found in bone and teeth. Absorbed fluoride which is not deposited in calcified tissues is excreted almost exclusively via the kidneys. Whereas skeletal bone and dentine accumulate fluoride throughout life, enamel of teeth incorporate fluoride only at the time of tooth formation. Fluoride substitutes for hydroxyl groups in the apatite, increasing the resistance to caries. In permanent teeth enamel maturation is completed at the age of seven to eight years, except in the third molars. Posteruptive fluoride uptake by enamel occurs only in the outer layer and depends on local oral fluoride levels. A linear relationship between fluoride exposure and caries resistance has been demonstrated. Over the years, the view has shifted from systemic fluoride being most effective for caries prevention to local oral exposure being most important. Acute toxic effects may be provoked by fluoride, and deaths have been reported after intake of very large doses from fluoride tablets. The main adverse outcomes from intake of excess doses of fluoride over time, are enamel fluorosis in children up to eight years of age, and bone fluorosis in older children and adults. Dental fluorosis causing mottled teeth is largely a cosmetic effect, whereas bone fluorosis causes stiff joints and a greater tendency to fractures. Tolerable upper intake levels (UL) for fluoride have been set by the American Institute of Medicine (IOM) and by the European Food Safety Authority (EFSA). In this report, we relate estimated fluoride intakes to the upper level set by EFSA. Intakes of the main dietary fluoride sources, water and tea, in different age groups were obtained from Norwegian dietary surveys. High fluoride intakes were estimated by applying the 95 percentile of fluoride concentrations in water obtained from 2001 fluoride analyses from Norwegian waterworks in the period between 2010 and 2018 and in tea obtained from a Polish study to the daily volume consumed. Fluoride intakes from recommended use of dental hygiene and caries prevention products were then added, plus a small fixed value for undescribed sources. The estimated 95 percentile fluoride exposure calculated this way was compared to the upper level, and scenarios with additional fluoride supplementation of 0.5, 1, 5 or 7 mg/day were developed. The estimated 95-percentile of fluoride exposure from water, tea and dental hygiene products alone (before fluoride from the suggested food supplement doses at 0.5, 1, and 7 mg/day were added) was found to exceed the upper level for 2-year old children and for adults. VKM concludes that all the suggested food supplement doses considered will cause the tolerable upper intake level to be exceeded in all age groups, except for the supplement doses of 0.5 in 9- and 13-year olds and 1 mg/day in 9 year olds. VKM emphasises that the current assessment of maximum limits for fluoride in food supplements is merely based on published reports concerning upper levels from the IOM (USA, 2001), Scientific Committee on Food (EU, 2003), Expert Group on Vitamins and Minerals (UK, 2003) and Nordic Nutrition Recommendations (Nordic Countries, 2012). VKM has not conducted any review of the literature for the current opinion, as this was outside the scope of the terms of reference from the NFSA.

• Meadow, Richard; Asare, Nana Yaa Ohene; Dalen, Knut Tomas; Finne, Merethe Aasmo; Junttila, Olavi & Kirkendall, Lawrence R. [Vis alle 13 forfattere av denne artikkelen] (2017). Risk assessment of insect-resistant and herbicide-tolerant genetically modified maize Bt11 for cultivation, import, processing, food and feed uses under Directive 2001/18/EC and Regulation (EC). Opinion of the Panel on Genetically Modified Organisms of the Norwegian Scientific Committee for Food Safety. Norwegian Scientific Committee for Food Safety (VKM). ISSN 9788282592796. Fulltekst i vitenarkiv
• Meadow, Richard; Asare, Nana Yaa Ohene; Finne, Merethe Aasmo; Junttila, Olavi; Kirkendall, Lawrence R. & Måren, Inger Elisabeth [Vis alle 13 forfattere av denne artikkelen] (2017). Risk assessment of insect-resistant and herbicide-tolerant genetically modified maize 1507 for cultivation, import, processing, food and feed uses under Directive 2001/18/EC (C/ES/01/01, C/NL/00/10) and Regulation (EC) No 1829/2003 (EFSA/GMO/NL/2004/02, EFSA/GMO/RX/1507). Opinion of the Panel on Genetically Modified Organisms of the Norwegian Scientific Committee for Food Safety. Norwegian Scientific Committee for Food Safety (VKM). ISSN 9788282592789. Fulltekst i vitenarkiv Vis sammendrag

  The Norwegian Environment Agency (NEA) and the Norwegian Food Safety Authority (NFSA) requested the Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) for an opinion of potential risks to biodiversity and agriculture in Norway associated with import of seeds for sowing, and cultivation of insect-resistant and herbicide-tolerant genetically modified maize 1507 under Directive 2001/18/EC (Notification C/ES/01/01). The notification is still pending for authorisation in the European Union. VKM is also requested to assess the applicant´s post-market environmental monitoring plan, and the management measures suggested in the draft implementing decision of the European Commission.

• Andreassen, Åshild Kristine; Sipinen, Ville Erling; Finne, Merethe Aasmo; Brandtzæg, Per; Dahl, Knut Helkås & Dalen, Knut Tomas [Vis alle 13 forfattere av denne artikkelen] (2016). Risk assessment of genetically modified carnation SHD-27531-4. Scientific opinion on genetically modified carnation SHD-27531-4 from Suntory Holdings Ltd. with modified petal colour for import as cut flowers for ornamental use under Part C of Directive 2001/18/EC (Application C/NL/13/01). Opinion of the Panel on Genetically Modified Organisms of the Norwegian Scientific Committee for Food Safety. Nofima. ISSN 9788282592246. Fulltekst i vitenarkiv
• Andreassen, Åshild Kristine; Sipinen, Ville Erling; Finne, Merethe Aasmo; Brandtzæg, Per; Dahl, Knut Helkås & Dalen, Knut Tomas [Vis alle 13 forfattere av denne artikkelen] (2016). Risk assessment of genetically modified carnation FLO-40685-2. Scientific opinion on genetically modified carnation FLO-40685-2 from Suntory Holdings Ltd. with modified petal colour for import as cut flowers for ornamental use under Part C of Directive 2001/18/EC (Application C/NL/13/02). Opinion of the Panel on Genetically Modified Organisms of the Norwegian Scientific Committee for Food Safety. Nofima. ISSN 9788282592253. Fulltekst i vitenarkiv
• Andreassen, Åshild Kristine; Bakke, Anne Marie; Dahl, Knut Helkås; Junttila, Olavi; Mikalsen, Arne & Sipinen, Ville Erling [Vis alle 14 forfattere av denne artikkelen] (2016). Final health and environmental risk assessment of genetically modified cotton 281-24-236 x 3006-210-23 (MXB-13). Scientific opinion on insect-resistant and glufosinate-tolerant, genetically modified MXB-13 from Dow AgroSciences for food and feed uses, import and processing under Regulation (EC) No 1829/2003 (Application EFSA/GMO/NL/2005/16). Opinion of the Panel on Genetically Modified Organisms of the Norwegian Scientific Committee for Food Safety. Nofima. ISSN 9788282591980. Fulltekst i vitenarkiv
• Andreassen, Åshild Kristine; Bakke, Anne Marie; Junttila, Olavi; Mikalsen, Arne; Sipinen, Ville Erling & Vikse, Rose [Vis alle 14 forfattere av denne artikkelen] (2016). Final health and environmental risk assessment of genetically modified LLcotton25. Scientific opinion on glufosinate-tolerant, genetically modified LLcotton25 from Bayer CropScience for food and feed uses, import and processing under Regulation (EC) No 1829/2003 (Application EFSA/GMO/NL/2005/13). Opinion of the Panel on Genetically Modified Organisms of the Norwegian Scientific Committee for Food Safety. Nofima. ISSN 9788282592000. Fulltekst i vitenarkiv
• Andreassen, Åshild Kristine; Bakke, Anne Marie; Junttila, Olavi; Mikalsen, Arne; Sipinen, Ville Erling & Vikse, Rose [Vis alle 14 forfattere av denne artikkelen] (2016). Final health and environmental risk assessment of genetically modified cotton GHB614. Scientific opinion on glyphosate-tolerant, genetically modified cotton GHB614 from Bayer CropScience for food and feed uses, import and processing under Regulation (EC) No 1829/2003 (Application EFSA/GMO/NL/2008/51). Opinion of the Panel on Genetically Modified Organisms of the Norwegian Scientific Committee for Food Safety. Nofima. ISSN 9788282591997. Fulltekst i vitenarkiv
• Andreassen, Åshild Kristine; Asare, Nana Yaa Ohene; Bakke, Anne Marie; Dahl, Knut Helkås; Dalen, Knut Tomas & Nielsen, Kaare Magne [Vis alle 13 forfattere av denne artikkelen] (2015). Final health and environmental risk assessment of genetically modified soybean MON 87701. Scientific opinion on insect resistant, genetically modified soybean MON 87701 from Monsanto for food and feed uses, import and processing under Regulation (EC) No 1829/2003 (Application EFSA/GMO/BE/2010/79). Opinion of the Panel on Genetically Modified Organisms of the Norwegian Scientific Committee for Food Safety. Nofima. ISSN 9788282591690. Fulltekst i vitenarkiv
• Andreassen, Åshild Kristine; Asare, Nana Yaa Ohene; Bakke, Anne Marie; Finne, Merethe Aasmo; Jevnaker, Anne Marthe & Junttila, Olavi [Vis alle 15 forfattere av denne artikkelen] (2015). Final health and environmental risk assessment of genetically modified carnation Moonberry IFD-25958-3. Scientific opinion on genetically modified carnation Moonberry IFD-25958-3 from Florigene with modified petal colour for import as cut flowers for ornamental use under Part C of Directive 2001/18/EC (Application C/NL /09/01). Opinion of the Panel on Genetically Modified Organisms of the Norwegian Scientific Committee for Food Safety. Nofima. ISSN 9788282591720. Fulltekst i vitenarkiv
• Andreassen, Åshild Kristine; Asare, Nana Yaa Ohene; Bakke, Anne Marie; Finne, Merethe Aasmo; Jevnaker, Anne Marthe & Junttila, Olavi [Vis alle 15 forfattere av denne artikkelen] (2015). Final health and environmental risk assessment of genetically modified carnation Moonlite 123.2.38. Scientific opinion on genetically modified carnation Moonlite 123.2.38 from Florigene with modified petal colour for import as cut flowers for ornamental use under Part C of Directive 2001/18/EC (Application C/NL/04/02). Opinion of the Panel on Genetically Modified Organisms of the Norwegian Scientific Committee for Food Safety. Norwegoan Scientific Committee for Food Safety (VKM). ISSN 9788282591706. Fulltekst i vitenarkiv
• Andreassen, Åshild Kristine; Asare, Nana Yaa Ohene; Bakke, Anne Marie; Dahl, Knut Helkås; Dalen, Knut Tomas & Nielsen, Kaare Magne [Vis alle 13 forfattere av denne artikkelen] (2015). Final health and environmental risk assessment of genetically modified soybean 356043. Scientific opinion on herbicide tolerant, genetically modified soybean 356043 from Pioneer Hi-Bred for food and feed uses, import and processing under Regulation (EC) No 1829/2003 (Application EFSA/GMO/UK/2007/43). Opinion of the Panel on Genetically Modified Organisms of the Norwegian Scientific Committee for Food Safety. Nofima. ISSN 9788282591683. Fulltekst i vitenarkiv
• Andreassen, Åshild Kristine; Asare, Nana Yaa Ohene; Bakke, Anne Marie; Finne, Merethe Aasmo; Jevnaker, Anne Marthe & Junttila, Olavi [Vis alle 15 forfattere av denne artikkelen] (2015). Final health and environmental risk assessment of genetically modified carnation Moonaqua 123.8.12. Scientific opinion on genetically modified carnation Moonaqua 123.8.12 from Florigene with modified petal colour for import as cut flowers for ornamental use under Part C of Directive 2001/18/EC (Application C/NL/06/01). Opinion of the Panel on Genetically Modified Organisms of the Norwegian Scientific Committee for Food Safety. Nofima. ISSN 9788282591713. Fulltekst i vitenarkiv
• Andreassen, Åshild Kristine; Bakke, Anne Marie; Dahl, Knut Helkås; Dalen, Knut Tomas; Finne, Merethe Aasmo & Mikalsen, Arne [Vis alle 14 forfattere av denne artikkelen] (2015). Final health and environmental risk assessment of genetically modified soybean MON 89788. Scientific opinion on herbicide tolerant, genetically modified soybean MON 89788 from Monsanto Company for food and feed uses, import and processing under Regulation (EC) No 1829/2003 (Application EFSA/GMO/NL/2006/36). Opinion of the Panel on Genetically Modified Organisms of the Norwegian Scientific Committee for Food Safety. Nofima. ISSN 9788282591645. Fulltekst i vitenarkiv
• Andreassen, Åshild Kristine; Bakke, Anne Marie; Dahl, Knut Helkås; Dalen, Knut Tomas; Finne, Merethe Aasmo & Mikalsen, Arne [Vis alle 14 forfattere av denne artikkelen] (2015). Food/feed and environmental risk assessment of herbicide tolerant genetically modified soybean A2704-12 for food and feed uses, import and processing under Regulation (EC) No 1829/2003 (EFSA/GMO/NL/2005/18). Opinion of the Panel on Genetically Modified Organisms of the Norwegian Scientific Committee for Food Safety. Nofima. ISSN 9788282591621. Fulltekst i vitenarkiv
• Andreassen, Åshild Kristine; Bakke, Anne Marie; Dahl, Knut Helkås; Dalen, Knut Tomas; Finne, Merethe Aasmo & Mikalsen, Arne [Vis alle 14 forfattere av denne artikkelen] (2015). Food/feed and environmental risk assessment of herbicide tolerant genetically modified soybean A5547-127 for food and feed uses, import and processing under Regulation (EC) No 1829/2003 (EFSA/GMO/NL/2008/52). Opinion of the Panel on Genetically Modified Organisms of the Norwegian Scientific Committee for Food Safety. Nofima. ISSN 9788282591638. Fulltekst i vitenarkiv
• Andreassen, Åshild Kristine; Asare, Nana Yaa Ohene; Bakke, Anne Marie; Finne, Merethe Aasmo; Jevnaker, Anne Marthe & Junttila, Olavi [Vis alle 15 forfattere av denne artikkelen] (2015). Final health and environmental risk assessment of genetically modified carnation Moonvelvet IFD-26407-2. Scientific opinion on genetically modified carnation Moonvelvet IFD-26407-2 from Florigene with modified petal colour for import as cut flowers for ornamental use under Part C of Directive 2001/18/EC (Application C/NL/09/02). Opinion of the Panel on Genetically Modified Organisms of the Norwegian Scientific Committee for Food Safety. Nofima. ISSN 9788282591737. Fulltekst i vitenarkiv

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