Nolwenn Briand

Briand N, Collas P (2020). Lamina-associated domains: peripheral matters and internal affairs. Genome Biol 21(1):85.

Briand N, Guénantin AC, Jeziorowska D, Shah A, Mantecon M, Capel E, Garcia M, Oldenburg A, Paulsen J, Hulot JS, Vigouroux C, Collas P (2018). The lipodystrophic hotspot lamin A p.R482W mutation deregulates the mesodermal inducer T/Brachyury and early vascular differentiation gene networks. Hum Mol Genet 27(8):1447-1459.

Oldenburg AR, Briand N, Sørensen AL, Cahyani I, Shah A, Moskaug JØ, Collas P (2017). A lipodystrophy-causing lamin A mutant alters conformation and epigenetic regulation of the anti-adipogenic MIR335 locus. J Cell Biol 216(9):2731-2743.

Guénantin AC, Briand N, Capel E, Dumont F, Morichon R, Provost C, Stillitano F, Jeziorowska D, Siffroi JP, Hajjar RJ, Fève B, Hulot JS, Collas P, Capeau J, Vigouroux C (2017). Functional human beige adipocytes from induced pluripotent stem cells. Diabetes 66(6):1470-1478.

Paulsen J, Sekelja M, Oldenburg AR, Barateau A, Briand N, Delbarre E, Shah, A, Sørensen AL, Vigouroux C, Biendia B, Collas P (2017). Chrom3D: three-dimensional genome modeling from Hi-C and nuclear lamin-genome contacts. Genome Biol 18(1):21.

Vadrot N, Duband-Goulet I, Cabet E, Attanda W, Barateau A, Vicart P, Gerbal F, Briand N, Vigouroux C, Oldenburg AR, Lund EG, Collas P, Buendia B (2015). The p.R482W substitution in A-type lamins deregulates SREBP1 activity in Dunnigan-type familial partial lipodystrophy. Hum Mol Genet 24(7):2069-20109.

Briand N, Prado C, Mabilleau G, Lasnier F, Le Lièpvre X, Covington JD, Ravussin E, Le Lay S, Dugail I (2014). Caveolin-1 expression and cavin stability regulate caveolae dynamics in adipocyte lipid store fluctuation. Diabetes 63(12):4032-44.

Briand N, Le Lay S, Sessa WC, Ferré P, Dugail I (2011). Distinct roles of endothelial and adipocyte caveolin-1 in macrophage infiltration and adipose tissue metabolic activity. Diabetes 60(2):448-53.

Le Lay S, Briand N, Blouin CM, Chateau D, Prado C, Lasnier F, Le Liepvre X, Hajduch E, Dugail I (2010). The lipoatrophic caveolin-1 deficient mouse model reveals autophagy in mature adipocytes. Autophagy 6(6):754-63.

Briand N, Dugail I, Le Lay S. 2011. Cavin proteins: New players in the caveolae field. Biochimie 93(1):71-7.

• Nothnagel, Patrizia Maria Christiane; Meslin, Paul-Arthur Richard; Wik, Jonas Aakre; Dufour, Damien; Strøm, Yunna Erika & Bjørås, Magnar [Vis alle 11 forfattere av denne artikkelen] (2026). Transient SUMOylation inhibition in human pre-adipocytes stably imprints a transcriptional beiging fate. Nucleic Acids Research (NAR). ISSN 0305-1048. 54(6), s. 1–22. doi: 10.1093/nar/gkag232. Fulltekst i vitenarkiv Vis sammendrag

  SUMOylation regulates chromatin states and transcriptional programs that preserve cellular identity, yet how perturbation of the SUMOylation pathway impacts adipocyte plasticity remains unclear. Here, we show that brief pharmacologic inhibition of SUMOylation in human pre-adipocytes using TAK-981 primes stable de novo beige differentiation in the presence of the PPARG agonist rosiglitazone. Transient TAK-981 exposure produces changes in the transcriptome and metabolism of mature adipocytes, including robust induction of canonical beiging markers like UCP1 and increased mitochondrial respiration. Mechanistically, ATAC-seq and RNA-sequencing revealed immediate chromatin remodeling and early mobilization of CEBP family members, followed by stable activation of CEBPA and PPARG regulatory networks. ChIP experiments demonstrated loss of H3K27me3 and gain of H3K27ac at PPAR response elements at thermogenic enhancers, and increased PPARG occupancy across the UCP1 regulatory unit. This mechanism is enforced by enhanced cAMP-PKA-p38 signaling and stabilization of beiging transcription activators. We propose that transient relief of SUMO-mediated repression unlocks dominant regulatory units, notably the UCP1 enhancer cluster, producing a monomorphic reprogramming toward adaptive thermogenesis. These findings identify SUMOylation as a reversible epigenetic barrier to adipocyte beiging and suggest that temporally controlled SUMO pathway inhibition combined with PPARG activation could be exploited to modulate adipose tissue thermogenic capacity.

• Pickering, Sarah Jai Hazell; Galigniana, Natalia Maricel; Abdelhalim, Mohamed; Sørensen, Anita Løvstad; Madsen-Østerbye, Julia-Kristina & Zucknick, Manuela [Vis alle 8 forfattere av denne artikkelen] (2026). Multimodal epigenetic and enhancer network remodeling shape the transcriptional landscape of human beige adipocytes. Communications Biology. doi: 10.1038/s42003-025-09469-8. Fulltekst i vitenarkiv Vis sammendrag

  Abstract Epigenetic regulation is a key determinant of adipocyte fate, driving the differentiation toward white or thermogenic beige phenotypes in response to environmental cues. To dissect the mechanisms orchestrating this plasticity in human adipocytes, we conducted an integrative analysis of transcriptomic, epigenomic and enhancer connectome dynamics throughout white and beige adipogenesis. Using a machine learning approach, we show that the white transcriptional program is tightly linked to promoter-level modulation of H3K27ac and chromatin accessibility, whereas the beige-specific induction of mitochondrial genes is driven by promoter remodeling of H3K4me3, underscoring distinct epigenetic mechanisms for white or beige specification. Adipocyte beiging is accompanied by a targeted reorganization of the 3D genome, characterized by increased recruitment of short-range enhancers controlling thermogenesis genes, enriched for C/EBP transcription factor binding sites. Our findings highlight the multimodal regulation of the beige adipocyte fate, driven by the interplay of chromatin state transitions, enhancer rewiring, and transcription factor dynamics.

• 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

• Nothnagel, Patrizia Maria Christiane; Meslin, Paul-Arthur Richard; Wik, Jonas Aakre; Strøm, Yunna Erika; Bjørås, Magnar & Enserink, Jorrit [Vis alle 10 forfattere av denne artikkelen] (2025). Transient SUMOylation Inhibition In Human Pre-adipocytes Stably Imprints a Transcriptional Beiging Fate. bioRxiv (preprint article). 54(6). doi: 10.1101/2025.03.07.642034. Fulltekst i vitenarkiv Vis sammendrag

  Abstract SUMOylation regulates chromatin states and transcriptional programs that preserve cellular identity, yet how transient perturbation of the SUMO pathway impacts adipocyte plasticity remains unclear. Here we show that brief pharmacologic inhibition of SUMO conjugation in human pre-adipocytes using TAK-981 primes stable de novo beige differentiation in the presence of the PPARG agonist rosiglitazone. Transient TAK-981 exposure before adipogenic induction produces long-lasting changes in the transcriptome and metabolism of mature adipocytes, including robust induction of canonical beiging markers like UCP1 and increased mitochondrial respiration. Mechanistically, ATAC-seq and transcription factor footprinting revealed immediate and durable chromatin remodeling and early mobilization of CEBP family members, followed by stable activation of CEBPA and PPARG regulatory networks. ChIP experiments demonstrated loss of H3K27me3 and gain of H3K27ac at PPAR response elements within key thermogenic enhancers, with increased PPARG occupancy across the UCP1 regulatory unit. This mechanism is enforced by enhanced cAMP-PKA-p38 signaling, and stabilization of beiging transcriptional activators. Our data support a model in which transient relief of SUMO-mediated repression unlocks dominant regulatory units, notably the UCP1 enhancer cluster, producing a monomorphic, cell type specific reprogramming toward adaptive thermogenesis. These findings identify SUMOylation as a reversible epigenetic barrier to adipocyte beiging and suggest that temporally controlled SUMO pathway inhibition combined with PPARG activation could be exploited to modulate adipose tissue thermogenic capacity. Graphical abstract SUMOylation restricts de novo differentiation of pre-adipocytes into beige adipocytes by repressing cAMP signaling and preventing epigenetic and transcriptional reprogramming of white adipocytes.

• Pickering, Sarah Jai Hazell; Abdelhalim, Mohamed Ibrahim Mohamed; Collas, Philippe & Briand, Nolwenn (2024). Alternative isoform expression of key thermogenic genes in human beige adipocytes. Frontiers in Endocrinology. 15. doi: 10.3389/fendo.2024.1395750. Fulltekst i vitenarkiv Vis sammendrag

  Background: The beneficial effect of thermogenic adipocytes in maintaining body weight and protecting against metabolic disorders has raised interest in understanding the regulatory mechanisms defining white and beige adipocyte identity. Although alternative splicing has been shown to propagate adipose browning signals in mice, this has yet to be thoroughly investigated in human adipocytes. Methods: We performed parallel white and beige adipogenic differentiation using primary adipose stem cells from 6 unrelated healthy subjects and assessed differential gene and isoform expression in mature adipocytes by RNA sequencing. Results: We find 777 exon junctions with robust differential usage between white and beige adipocytes in all 6 subjects, mapping to 562 genes. Importantly, only 10% of these differentially spliced genes are also differentially expressed, indicating that alternative splicing constitutes an additional layer of gene expression regulation during beige adipocyte differentiation. Functional classification of alternative isoforms points to a gain of function for key thermogenic transcription factors such as PPARG and CITED1, and enzymes such as PEMT, or LPIN1. We find that a large majority of the splice variants arise from differential TSS usage, with beige-specific TSSs being enriched for PPARγ and MED1 binding compared to white-specific TSSs. Finally, we validate beige specific isoform expression at the protein level for two thermogenic regulators, PPARγ and PEMT. Discussion: These results suggest that differential isoform expression through alternative TSS usage is an important regulatory mechanism for human adipocyte thermogenic specification.

• Potolitsyna, Evdokiia; Pickering, Sarah Jai Hazell; Bellanger, Aurelie Nathalie Pascale; Germier, Thomas Lodewijk Guy; Collas, Philippe & Briand, Nolwenn (2024). Cytoskeletal rearrangement precedes nucleolar remodeling during adipogenesis. Communications Biology. 7. doi: 10.1038/s42003-024-06153-1. Fulltekst i vitenarkiv Vis sammendrag

  Differentiation of adipose progenitor cells into mature adipocytes entails a dramatic reorganization of the cellular architecture to accommodate lipid storage into cytoplasmic lipid droplets. Lipid droplets occupy most of the adipocyte volume, compressing the nucleus beneath the plasma membrane. How this cellular remodeling affects sub-nuclear structure, including size and number of nucleoli, remains unclear. We describe the morphological remodeling of the nucleus and the nucleolus during in vitro adipogenic differentiation of primary human adipose stem cells. We find that cell cycle arrest elicits a remodeling of nucleolar structure which correlates with a decrease in protein synthesis. Strikingly, triggering cytoskeletal rearrangements mimics the nucleolar remodeling observed during adipogenesis. Our results point to nucleolar remodeling as an active, mechano-regulated mechanism during adipogenic differentiation and demonstrate a key role of the actin cytoskeleton in defining nuclear and nucleolar architecture in differentiating human adipose stem cells.

• Dapsance, Florian; Hou, Jie; Dufour, Damien; Boccara, Charlotte; Briand, Nolwenn & Martinsen, Ørjan Grøttem (2023). Adipose Tissue Characterization With Electrical Impedance Spectroscopy and Machine Learning. IEEE Sensors Letters. 7(10). doi: 10.1109/LSENS.2023.3317921. Fulltekst i vitenarkiv Vis sammendrag

  Biological tissues have variable passive electrical properties depending on their cellular constitution. Electrical impedance spectroscopy (EIS) is commonly used to monitor cell and tissue characteristics. By measuring the impedance of a sample at various frequencies, it is possible to collect information regarding cell size and shape, cell membrane properties, or cytoplasm conductivity. From the perspective of longitudinal structural monitoring, bioimpedance measurements outrank traditional tissue analysis methods, such as fixation and slicing, owing to their nondestructive nature. Machine learning can be used to automatically process the impedance data and make real-time classifications of tissue types. Here, we present preliminary results on ex-vivo mouse adipose tissue measurements using EIS and further data processing and classification using machine learning models.

• Potolitsyna, Evdokiia; Pickering, Sarah Jai Hazell; Tooming-Klunderud, Ave; Collas, Philippe & Briand, Nolwenn (2022). De novo annotation of lncRNA HOTAIR transcripts by long-read RNA capture-seq reveals a differentiation-driven isoform switch. BMC Genomics. 23(1). doi: 10.1186/s12864-022-08887-w. Fulltekst i vitenarkiv Vis sammendrag

  Background LncRNAs are tissue-specific and emerge as important regulators of various biological processes and as disease biomarkers. HOTAIR is a well-established pro-oncogenic lncRNA which has been attributed a variety of functions in cancer and native contexts. However, a lack of an exhaustive, cell type-specific annotation questions whether HOTAIR functions are supported by the expression of multiple isoforms. Results Using a capture long-read sequencing approach, we characterize HOTAIR isoforms expressed in human primary adipose stem cells. We find HOTAIR isoforms population displays varied splicing patterns, frequently leading to the exclusion or truncation of canonical LSD1 and PRC2 binding domains. We identify a highly cell type-specific HOTAIR isoform pool regulated by distinct promoter usage, and uncover a shift in the HOTAIR TSS usage that modulates the balance of HOTAIR isoforms at differentiation onset. Conclusion Our results highlight the complexity and cell type-specificity of HOTAIR isoforms and open perspectives on functional implications of these variants and their balance to key cellular processes.

• Potolitsyna, Evdokiia; Pickering, Sarah Jai Hazell; Germier, Thomas Lodewijk Guy; Collas, Philippe & Briand, Nolwenn (2022). Long non-coding RNA HOTAIR regulates cytoskeleton remodeling and lipid storage capacity during adipogenesis. Scientific Reports. 12(1). doi: 10.1038/s41598-022-14296-6. Fulltekst i vitenarkiv Vis sammendrag

  Abstract The long non-coding RNA HOTAIR is the most differentially expressed gene between upper- and lower-body adipose tissue, yet its functional significance in adipogenesis is unclear. We report that HOTAIR expression is transiently induced during early adipogenic differentiation of gluteofemoral adipose progenitors and repressed in mature adipocytes. Upon adipogenic commitment, HOTAIR regulates protein synthesis pathways and cytoskeleton remodeling with a later impact on mature adipocyte lipid storage capacity. Our results support novel and important functions of HOTAIR in the physiological context of adipogenesis.

• Briand, Nolwenn & Collas, Philippe (2020). Lamina-associated domains: Peripheral matters and internal affairs. Genome Biology. ISSN 1465-6906. 21:85, s. 1–25. doi: 10.1186/s13059-020-02003-5. Fulltekst i vitenarkiv Vis sammendrag

  At the nuclear periphery, associations of chromatin with the nuclear lamina through lamina-associated domains (LADs) aid functional organization of the genome. We review the organization of LADs and provide evidence of LAD heterogeneity from cell ensemble and single-cell data. LADs are typically repressive environments in the genome; nonetheless, we discuss findings of lamin interactions with regulatory elements of active genes, and the role lamins may play in genome regulation. We address the relationship between LADs and other genome organizers, and the involvement of LADs in laminopathies. The current data lay the basis for future studies on the significance of lamin-chromatin interactions in health and disease.

• Briand, Nolwenn & Collas, Philippe (2018). Laminopathy-causing lamin A mutations reconfigure lamina-associated domains and local spatial chromatin conformation. Nucleus. ISSN 1949-1034. 9(1), s. 216–226. doi: 10.1080/19491034.2018.1449498. Fulltekst i vitenarkiv Vis sammendrag

  The nuclear lamina contributes to the regulation of gene expression and to chromatin organization. Mutations in A-type nuclear lamins cause laminopathies, some of which are associated with a loss of heterochromatin at the nuclear periphery. Until recently however, little if any information has been provided on where and how lamin A interacts with the genome and on how disease-causing lamin A mutations may rearrange genome conformation. Here, we review aspects of nuclear lamin association with the genome. We highlight recent evidence of reorganization of lamin A-chromatin interactions in cellular models of laminopathies, and implications on the 3-dimensional rearrangement of chromatin in these models, including patient cells. We discuss how a hot-spot lipodystrophic lamin A mutation alters chromatin conformation and epigenetic patterns at an anti-adipogenic locus, and conclude with remarks on links between lamin A, Polycomb and the pathophysiology of laminopathies. The recent findings presented here collectively argue towards a deregulation of large-scale and local spatial genome organization by a subset of lamin A mutations causing laminopathies.

• Briand, Nolwenn; Cahyani, Inswasti; Madsen-Østerbye, Julia-Kristina Jensen; Paulsen, Jonas; Rønningen, Torunn & Sørensen, Anita Løvstad [Vis alle 7 forfattere av denne artikkelen] (2018). Lamin A, Chromatin and FPLD2:Not ust a Peripheral Ménage-à-Trois. Frontiers in Cell and Developmental Biology. 6. doi: 10.3389/fcell.2018.00073. Fulltekst i vitenarkiv Vis sammendrag

  At the nuclear periphery, the genome is anchored to A- and B-type nuclear lamins in the form of heterochromatic lamina-associated domains. A-type lamins also associate with chromatin in the nuclear interior, away from the peripheral nuclear lamina. This nucleoplasmic lamin A environment tends to be euchromatic, suggesting distinct roles of lamin A in the regulation of gene expression in peripheral and more central regions of the nucleus. The hot-spot lamin A R482W mutation causing familial partial lipodystrophy of Dunnigan-type (FPLD2), affects lamin A association with chromatin at the nuclear periphery and in the nuclear interior, and is associated with 3-dimensional (3D) rearrangements of chromatin. Here, we highlight features of nuclear lamin association with the genome at the nuclear periphery and in the nuclear interior. We address recent data showing a rewiring of such interactions in cells from FPLD2 patients, and in adipose progenitor and induced pluripotent stem cell models of FPLD2. We discuss associated epigenetic and genome conformation changes elicited by the lamin A R482W mutation at the gene level. The findings argue that the mutation adversely impacts both global and local genome architecture throughout the nucleus space. The results, together with emerging new computational modeling tools, mark the start of a new era in our understanding of the 3D genomics of laminopathies.

• Briand, Nolwenn; Guénantin, Anne-Claire; Jeziorowska, Dorota; Shah, Akshay; Mantecon, Matthieu & Capel, Emilie [Vis alle 12 forfattere av denne artikkelen] (2018). The lipodystrophic hotspot lamin A p.R482W mutation deregulates the mesodermal inducer T/Brachyury and early vascular differentiation gene networks. Human Molecular Genetics. ISSN 0964-6906. 27(8), s. 1447–1459. doi: 10.1093/hmg/ddy055. Fulltekst i vitenarkiv
• Guénantin, Anne-Claire; Briand, Nolwenn; Capel, Emilie; Dumont, Florent; Morichon, Romain & Provost, Claire [Vis alle 15 forfattere av denne artikkelen] (2017). Functional human beige adipocytes from induced pluripotent stem cells. Diabetes. ISSN 0012-1797. 66(6), s. 1470–1478. doi: 10.2337/db16-1107. Fulltekst i vitenarkiv
• Oldenburg, Anja; Briand, Nolwenn; Sørensen, Anita Løvstad; Cahyani, Inswasti; Shah, Akshay & Moskaug, Jan Øivind [Vis alle 7 forfattere av denne artikkelen] (2017). A lipodystrophy-causing lamin A mutant alters conformation and epigenetic regulation of the anti-adipogenic MIR335 locus. Journal of Cell Biology. ISSN 0021-9525. 216(9), s. 2731–2743. doi: 10.1083/jcb.201701043. Fulltekst i vitenarkiv
• Paulsen, Jonas; Sekelja, Monika; Oldenburg, Anja; Barateau, Alice; Briand, Nolwenn & Delbarre, Erwan [Vis alle 11 forfattere av denne artikkelen] (2017). Chrom3D: Three-dimensional genome modeling from Hi-C and nuclear lamin-genome contacts. Genome Biology. ISSN 1465-6906. 18:21, s. 1–15. doi: 10.1186/s13059-016-1146-2. Fulltekst i vitenarkiv Vis sammendrag

  Current three-dimensional (3D) genome modeling platforms are limited by their inability to account for radial placement of loci in the nucleus. We present Chrom3D, a user-friendly whole-genome 3D computational modeling framework that simulates positions of topologically-associated domains (TADs) relative to each other and to the nuclear periphery. Chrom3D integrates chromosome conformation capture (Hi-C) and lamin-associated domain (LAD) datasets to generate structure ensembles that recapitulate radial distributions of TADs detected in single cells. Chrom3D reveals unexpected spatial features of LAD regulation in cells from patients with a laminopathy-causing lamin mutation. Chrom3D is freely available on github.

• Vadrot, Nathalie; Duband-Goulet, Isabelle; Cabet, Eva; Attanda, Wikayatou; Barateau, Alice & Vicart, Patrick [Vis alle 13 forfattere av denne artikkelen] (2014). The p.R482W substitution in a-type lamins deregulates SREBP1 activity in dunnigan-type familial partial lipodystrophy. Human Molecular Genetics. ISSN 0964-6906. 24(7), s. 2096–2109. doi: 10.1093/hmg/ddu728. Fulltekst i vitenarkiv

Se alle arbeider i NVA

• Bryne, Sandra Kristine Stølen; Dufour, Damien; Briand, Nolwenn & Boccara, Charlotte (2025). Does poor sleep during adolescence lead to metabolic disorders later in life? – Targeted chemogenetic models of sleep deprivation in mice. Fulltekst i vitenarkiv Vis sammendrag

  Poor sleep and obesity are concurrent health epidemics in adolescents. This is especially concerning given that adolescents are getting less and less sleep as technology invades their bedrooms. Several studies point to adolescence as a critical period for sleep and adipose tissue development, implying that poor sleep during this period might alter the normal development of adipose tissue and cause metabolic imbalance. To investigate whether adolescent sleep quality contributes to the emergence of metabolic dysfunctions later in life, we propose to establish new rodent models of reversible sleep deprivation for which we can turn on and off sleep quality/quantity at specific developmental windows. Here we present preliminary data of our new chemogenetic model for which we can disturb sleep at specific time points between postnatal day P21 and P54 by targeting brain nuclei promoting wakefulness through the stimulation of GABAergic neurons in the ventral pallidum. We assessed the sleep amounts and quality of these animals by recording their neural (EEG) and muscular (EMG) activity. Metabolic parameters during and after sleep disturbances were assessed with metabolic cages (energy expenditure, respiratory exchange rate, food intake, weight, activity), adipose tissue histology and plasma collection (hormones and proteins). Our preliminary results indicate successful sleep deprivation concomitant with decreased respiratory exchange rate indicating a shift toward lipid oxidation as a primary energy source.

• Bryne, Sandra Kristine Stølen; Dufour, Damien; Briand, Nolwenn & Boccara, Charlotte (2025). Can poor sleep during adolescence lead to metabolic disorders later in life?- Targeted chemogenetic models of sleep deprivation in mice. Fulltekst i vitenarkiv Vis sammendrag

  Obesity and poor sleep are concurrent health epidemics in adolescents. This is especially concerning given that adolescents are getting less and less sleep as technology invades their bedrooms. Several studies point to adolescence as a critical period for sleep and adipose tissue development, implying that poor sleep during this period might alter the normal development of adipose tissue. To investigate whether adolescent sleep quality contributes to the emergence of metabolic dysfunctions later in life, we propose to establish new rodent models of reversible sleep deprivation for which we can turn on/off sleep quality/quantity at specific developmental windows. Here we present preliminary data of our new chemogenetic model for which we can disturb sleep at specific time points between postnatal day P21 and P54 by targeting brain nuclei promoting wakefulness through the stimulation of GABAergic neurons in the ventral pallidum. We assessed the sleep amounts and quality of these animals by recording their neural (EEG) and muscular (EMG) activity. Metabolic parameters during and after sleep disturbances were assessed with metabolic cages (energy expenditure, respiratory exchange rate, food/water intake, weight), adipose tissue histology and plasma collection (hormones and proteins). Our preliminary results indicate successful sleep deprivation concomitant with decreased respiratory exchange rate indicating a shift toward lipid oxidation as a primary energy source.

• Bryne, Sandra Kristine Stølen; Dufour, Damien; Briand, Nolwenn & Boccara, Charlotte (2024). Inducible mouse models of adolescent sleep deprivation: the role of sleep in metabolic health. Fulltekst i vitenarkiv
• Pickering, Sarah Jai Hazell; Briand, Nolwenn; Collas, Philippe & Zucknick, Manuela (2025). White and beige adipogenesis: Transcriptomic and epigenetic insights into human adipocyte plasticity. Universitetet i Oslo. ISSN 9788234806742. Fulltekst i vitenarkiv Vis sammendrag

  Adipose tissue plasticity plays a critical role in maintaining metabolic homeostasis and represents an important focus of research in a world with a growing prevalence of obesity and type 2 diabetes. The presence of thermogenic beige adipocytes within white adipose tissue correlates with a lean, metabolically healthy phenotype in adults. Yet, the mechanisms underlying individual variations in thermogenic capacity remain poorly understood. To understand the regulation of beige adipocyte identity and lineage specification, we investigated the transcriptome and 3D epigenome of human white and beige mature adipocytes and mapped early adipogenic differentiation at single-cell resolution. As a model, we differentiated primary adipose stem cells isolated from six unrelated individuals in the presence or absence of the beiging agent rosiglitazone, generating matched beige and white adipocytes. We define a range of cell states among adipose progenitors during early white and beige adipogenesis, including several bipotential progenitor populations that can produce both white and beige adipocytes. Further, we characterised the transcriptomic and epigenetic landscape of mature adipocytes and found that alternative isoform usage makes a significant contribution to the functional transcriptome of beige versus white adipocytes. We discovered a novel beige-specific isoform of PEMT and alternative TSS usage of key transcription factor PPARy. In addition, we identified increased active epigenetic marks and enhancer contacts in beige adipocytes. White adipocytes, in comparison, have an enrichment for different epigenetic markers, highlighting distinctive features of the epigenome between beige and white adipocytes. Together this thesis provides insights into the transcriptional heterogeneity of adipose progenitors, early adipogenesis and the epigenetic regulation of healthy white and beige cultured adipocytes.

• Boccara, Charlotte; Gosse, Laure; Briand, Nolwenn & Dufour, Damien (2023). Innervation of adipose tissue in mice. Sorbone Universite. Fulltekst i vitenarkiv

Se alle arbeider i NVA