Abstract 524: Role of Transmembrane Protein 55B in Insulin Signaling and Hepatic Lipid Metabolism

Hepatic steatosis is the leading cause of liver disease in the United States and is associated with increased risk of cardiovascular disease. Insulin resistance appears to be a major determinant of hepatic steatosis, as improper hepatic insulin signaling stimulates lipogenesis and dysregulates lipoprotein secretion, resulting in fat accumulation in the liver. Insulin signal transduction is dependent on phosphatidylinositol-4,5-biphosphate (PIP2) conversion to phosphatidylinositol-3,4,5-biphosphate (PIP3), which results in activation of AKT. Transmembrane protein 55B (TMEM55B), a gene we recently identified as a novel regulator of cellular cholesterol metabolism, encodes a phosphatidylinositol phosphatase that converts PIP2 to phosphatidylinositol-5-phosphate (PI5P). PI5P has also been shown to activate AKT; however, the physiological effects of this pathway are less well understood. In the first in vivo model of Tmem55b modulation, we found that hepatic Tmem55b knockdown in Western diet-fed C57BL/6 mice c...