Suzanne E. Barbour
University of Georgia, USA
Title: Novel Roles of iPLA2ï¢ in Hepatic Lipid Metabolism
Biography
Biography: Suzanne E. Barbour
Abstract
The Group VIA phospholipase A2 (iPLA2b) is highly expressed in metabolically active tissues and recent studies have connected the enzyme to a variety of metabolic diseases. Our studies are focused on the role of the enzyme in fatty liver disease. Exogenous unsaturated fatty acids (UFA) suppress expression and processing of sterol regulatory element binding protein-1 (SREBP-1), a transcription factor that regulates lipogenic gene expression in the liver. We compared hepatic lipid metabolism in iPLA2b-/- and wild type mice, to test the hypothesis that the iPLA2b might be a source of endogenous UFA that regulate SREBP-1 and thereby modulate fatty liver. As expected, iPLA2b-/- livers contained more SREBP-1c and exhibited increased processing of this protein, compared to wild type livers. The changes in SREBP-1 expression/ processing correlated with increased lipogenic gene expression, synthesis of fatty acids and triacylglycerols (TAG), and TAG mass in iPLA2b-/- livers. We also observed evidence of reduced secretion of TAG, cholesterol, and cholesterol ester in iPLA2b-/- hepatocytes, suggesting that TAG accumulation in iPLA2b-/- livers is the result of both increased synthesis and reduced secretion. Our studies indicate that iPLA2b-derived lipids contribute to pathogenesis of at least two metabolic diseases. Identification of the bioactive lipids and their mechanisms of action may uncover novel ways to treat diabetes mellitus and fatty liver disease.