Grant: Operating Grant

Obesity is strongly associated with excessive fat storage in multiple tissues including the liver, where this fat deposition leads to abnormal liver functions and risk for cardiovascular disease and diabetes. Increased liver fat deposition stimulates the export of particles that carry bad cholesterol (LDL). We have shown that a protein called Ces3/TGH plays an important role in regulating the cholesterol export from the liver into blood. We have developed mice that are deficient in this protein and have shown that these animals have less harmful blood lipid levels and are protected from high-fat diet-induced cardiovascular disease, fat accumulation in the liver and have improved sugar metabolism. Therefore, decreasing the function of this protein would seem beneficial in treatment of obesity-related metabolic complications. In the proposed research we plan to investigate the mechanisms by which Ces3/TGH regulates fat absorption, fat storage, address mutations in this protein in humans, and research a novel animal model in effort to develop therapeutics for the treatment of obesity.