Metabolic determinants of hepatic lipotoxicity

Serum free fatty acids (FFAs) are typically elevated in individuals who suffer from obesity and type-2 diabetes. Abnormal hepatic lipid accumulation caused by FFA overload leads to a condition known as nonalcoholic fatty liver disease (NAFLD), which is estimated to effect up to 30% of the U.S. population. As a result, NAFLD is now the leading cause of referrals to hepatology clinics in the U.S. Unfortunately, the factors that influence disease progression are poorly understood, and therapeutic strategies for preventing or reversing NAFLD are limited. Our research aims to identify the lipid intermediates and signaling molecules that induce lipotoxic cell death in FFA-treated hepatic cells and to determine the mechanism by which these species promote abnormal cell metabolism and oxidative stress.

Funding support: NSF CAREER
Graduate students: Rob Egnatchik, Alexandra Leamy
Key collaborators: Masa Shiota (MP&B), David Jacobson (MP&B), Robb Flynn (Surgery)