MIRBATWAT · Role of miRNAs in brown and white adipose tissue differentiation and function

Mammals have two types of fat: brown and white, with opposing functions. The white adipose tissue (WAT) is an important regulator of the whole body homeostasis that also serves to store energy in form of triglycerides (TGs). The main function of the brown adipose tissue (BAT) is to catabolize lipids in order to produce heat, a function that can be induced by cold exposure or diet. Disruption of the normal differentiation or development of the WAT causes ectopic lipid storage and severe pathology in both humans and experimental animals. Increased BAT development leads to increased energy expenditure without causing dysfunction in other tissues, and is associated with a lean and healthy phenotype, outlining the manipulation of the fat stores as an obvious therapeutic objective. With the proposed research we will identify miRNAs and other factors that regulate BAT and WAT differentiation and function. We will distinguish the miRNAs that specifically regulate brown or white adipogenesis and are expressed in the respective precursors, and establish them as signatures for either cell type. We will also identify the molecular mechanisms of action of the identified miRNAs in regulation of adipose tissue differentiation and metabolism. Using in vitro and in vivo systems, linage tracing studies, transgenic animals, as well as cohorts of human patients, we will determine the origin of the beige cells within the SAT, establish their importance in the regulation of metabolism in vivo, and develop novel strategies to induce the brown fat differentiation and function. Finally, we will discover ways to exclusively silence miRNAs in the brown fat will that will allow us not only to investigate the miRNAs function specifically in the brown fat, but also to develop new strategies for treatment of dyslipedaemia, diabetes and obesity.