Nutritional regulation of transcription
The ability to sense the environmental fluctuations of nutrients is a requisite for living cells. Cells have acquired an intricate system for detecting and responding to changes in nutrient levels and their metabolites. Nutrient sensing transcription factors, such as PPARs, LXRs and ChREBP, play essential roles in regulating fat and sugar metabolism, adipose tissue dynamics, cholesterol transport and disposal, and inflammatory responses.
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.
- 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.
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).
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).
The University of Oslo, The Research Council of Norway, The Throne-Holst Foundation, and The Norwegian Seafood Research Fund.