Eric Yen

Our research focuses on the physiological functions of triacylglycerol (triglyceride; TG) synthesis. TG serves as a storage and transport molecule of bioactive fatty acids and its synthesis is essential for many biological processes, including the absorption of dietary fat and the production of milk. Excessive accumulation of TG, however, leads to obesity and related metabolic diseases, such as type 2 diabetes. Using genetically engineered mice, we examine the physiological functions of enzymes involved in the synthesis of TG. One current focus is on the acyl CoA:monoacylglycerol acyltransferase MGAT2, which mediates fat absorption in the small intestine. Mice lacking the enzyme are protected against obesity and other metabolic disorders normally induced by high-fat feeding. Interestingly, they absorb a normal quantity of dietary fat but exhibit increases in energy expenditure. We are now combining biochemical and systems biology approaches to understand the molecular mechanisms by which intestinal lipid metabolism regulates systemic energy balance. This is a research area of critical importance. Several MGAT2 inhibitors have been developed and are being tested for efficacy. Our on-going research has also expanded into other functions of MGATs and additional genetic and dietary factors modulating energy balance. The ultimate goals of these studies are to better understand the fundamental process of fat assimilation and to explore new approaches to prevent or treat obesity and other metabolic diseases associated with excessive fat intake and energy storage.