Abstract 1146: Vitamin A Status Regulates Glucose and Lipid Homeostasis in Rats
Since elevation of hepatic vitamin A (VA, retinol) content in diabetic patients was observed before, we hypothesized that VA status may play a role in glucose and lipid homeostasis. Recently, we observed that retinoids synergized with insulin to induce hepatic glucokinase gene expression. To further examine our hypothesis, male Zucker lean rats were fed with VA deficient (VAD) or sufficient (VAS) diet before their plasma and tissue samples were analyzed. The content of liver glycogen; weights of body, liver and epididymal fat; and levels of plasma glucose, triglycerides, insulin, and leptin, were lower in VAD than in VAS rats. VAD rats disposed glucose more rapidly than VAS rats did in a glucose tolerance test, whereas both groups had the similar response to insulin in an insulin tolerance test. When analyzed by microarray and confirmed by real time PCR, the expression levels of hepatic genes involved in glucose utilization and fatty acid biosynthesis were lower in VAD than in VAS rats. In primary hepatocytes, retinoic acid transiently synergized with insulin to induce the expression of sterol regulatory element-binding protein 1c, a critical transcriptional activator for lipogenesis, and resulted in elevation of the expression of its down stream targeted gene, fatty acid synthase. It does so through activation of retinoid X receptor, but not retinoic acid receptor. These results demonstrated that VA status regulates glucose and lipid homeostasis in rats. It is achieved, at least in part, through regulating hepatic gene expression. Further work is needed to understand the underlying molecular mechanisms.