The role of Plins and lipid droplets for hepatic and muscular insulin resistance
Obesity and associated complications are strong determinants for reduced life expectancy and development of chronic diseases in the Norwegian population. At a molecular level, the main difference between normal weighted and obese individuals is massive accumulation of excess lipids within lipid droplet (LD) in adipose tissue, and often in ectopic organs such as liver and muscle. Such ectopic accumulation is a strong predictor for clinical complications, including insulin resistance and type 2 diabetes mellitus (T2D). Current strategies to reduce the risk of development of T2D include dietary advice toward a healthier diet combined with various medications of insulin resistant individuals. Current medical approaches to treat T2D targets broadly with a secondary improvement of insulin sensitivity. Development of drugs to target alternative molecular pathways are of high priority to reduce future health costs linked to obesity.
A strong association between accumulation of LD organelles and lipid-mediated diseases is well known. In fact, LD often serve as pathological markers for the lipid diseases in question. Still, the contribution of accumulated LD organelles for disease development is poorly understood. The overall goal of this project is to address if accumulation of LD in liver and muscle 1) protects against, 2) promotes, 3) or have negligible impact on energy metabolism, insulin sensitivity and progression to chronic T2D. The project combines metabolic phenotyping of genetically modified mouse models with defective lipid droplet storage (Plin null) with state of the art molecular techniques carefully selected to investigate the influence of the LD organelle on organ metabolism and function. A number of parallel projects are currently ongoing related to various Plin null mice generated by Dalen at National Institutes of Health (NIH) in 2005-2009. The work carried out in Norway is coordinated by associate Professor Knut Tomas Dalen, in collaboration with Prof. Alan R. Kimmel at NIDDK, NIH, US.
- Samarbeid med National Institutes of Health