About the project
The main objective of this project is to strengthen the molecular understanding of nutrition-induced lifestyle diseases, such as non-alcoholic fatty liver disease (NAFLD), Type 2 diabetes (T2D), and Metabolic syndrom (MetS). Using both in vivo and in vitro approaches we are studying the crosstalk between nutrients, nuclear receptors and other nutrient sensing transcription factors, underlying the transcriptional regulation of metabolism and differentiation.
Ongoing research
- Regulation of glycolytic and lipogenic genes by complexed LXR and ChREBP.
- Sugar-induced O-linked GlcNAc modifications of transcription factors.
- Identification, design and synthesis of novel PPAR agonists of marine origin.
- Salmon proteins and salmon protein hydrolysates as nutraceuticals with health benefits.
Outcomes/Recent findings
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LXRα regulates ChREBPα transactivity in a target gene-specific manner through an agonist-modulated LBD-LID interaction (Fan et al. 2020 Cells)
- Molecular modelling, synthesis, and biological evaluations of an oxohexadecenoic analogue as a PPARα-selective agonist (Arnesen et al. 2019 Bioorg Med Chem).
- Total synthesis and pharmacological characterization of two marine oxohexadecenoic acids (Sæther et al. 2018 Eur J Med Chem).
- O-GlcNAc site-mapping of liver X receptor-α and O-GlcNAc transferase (Fan et al. 2018 Biochem Biophys Res Commun ).
- LXRα Regulates Hepatic ChREBPα Activity and Lipogenesis upon Glucose, but Not Fructose (Fan et al. 2017 Nutrients).
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Identification of two oxohexadecenoic acids from the marine diatome Chaetoceros karianus with PPARα/γ dual agonist activity (Moldes-Anaya, Sæther et al. 2017 Mar Drugs).
- Liver X receptor regulates hepatic nuclear O-GlcNAc signaling and carbohydrate responsive element-binding protein activity (Bindesbøll et al. 2015 J Lipid Res).
Funding
The University of Oslo, The Research Council of Norway, The Throne-Holst Foundation, and The Norwegian Seafood Research Fund.
Collaborations
- Trond Vidar Hansen, Dept. of Pharmaceutical Chemistry , UiO: Chemical synthesis of PPAR-activating compounds.
- Ingebrigt Sylte, Dept. of Medical Biology, UiT The Arctic University of Norway: 3D in silico docking of PPAR-agonists.
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Cathrine Rein Carlson, Inst. for Experimental Medical Research, OUS: Interaction mapping using peptide arrays
- Steinar Paulsen, MabCent - SFI, UiT The Arctic University of Norway: HTS for novel nuclear receptor ligands from marine invertebrates.
- Knut Tomas Dalen, Dept. of Nutrition, UiO: In vivo, ex vivo and in vitro effects of salmon fishmeal.
- Ola Ween, Møreforsking AS: In vitro digestion of marin proteins and peptides and bioactivity assays.
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Hilde Nebb, prev. Dept. of Nutrition, UiO: Metabolic regulation and life style diseases.