Comparison of insulin and retinoid responses of hepatocytes from Zucker lean and fatty rat fed with chow and a synthetic vitamin A sufficient diet

The mechanisms of hepatic insulin resistance at transcription level remain unknown. This study aims to compare the insulin and retinoid mediated responses of hepatocytes from Zucker lean (ZL) and fatty (ZF) rats fed with chow or a synthetic vitamin A sufficient diet, TestDiet 5755 (TD). Primary hepatocytes were isolated from chow‐fed or TD‐fed ZL and ZF rats. The expression levels of Gck, Srebf‐1c and Pklr in response to insulin and retinoic acid (RA) were determined by RT‐PCR. We showed here that, in hepatocytes of ZL rat fed with chow or TD, RA synergized with insulin to induce the expression of both Gck and Srebf‐1c. The fold of induction was greater in hepatocytes of ZL rats on TD compared with that on chow. Hepatocytes from ZF rat on chow or TD diet had impaired regulation of Gck and Srebf‐1c expression mediated by insulin and retinoids. The insulin and RA mediated response was impaired to a similar level in hepatocytes of ZF rats on both diets. Pklr gene expression was not responsive to insulin and RA in hepatocytes from either ZL or ZF rats. We demonstrated here that insulin and retinoid mediated gene expression pattern in hepatocytes was similar in rats fed chow or synthetic diet. The impaired insulin response observed in the hepatocytes from chow‐fed ZF rats remained in the hepatocytes from ZF rats fed on a synthetic diet. It indicated a possibility of using synthetic diet to investigate how nutrient contributes to the impairment. Grant Funding Source : American Heart Association