Effects of vitamin A status on the responses of the hepatic genes’ expression to insulin and retinoic acid in primary hepatocytes from Zucker lean and fatty rats

Insulin‐mediated regulation of hepatic gene expression plays a key role in glucose and lipid homeostasis. This study was aimed to examine the hepatic gene expression in response to insulin and retinoic acid (RA) treatments in primary hepatocytes from Zucker rats of different vitamin A (VA) status. Primary hepatocytes were isolated from Zucker lean (ZL) or fatty (ZF) rats fed either vitamin A sufficient (VAS) or deficient diet (VAD) for 8 weeks after weaning. The mRNA levels of Gck, Pck1, Srebp‐1c and Pklr after insulin and RA stimulation for 6 hours were determined using real‐time PCR. In hepatocytes of ZL rats on either diet, insulin synergized with RA to induce the expression of Gck and Srebp‐1c. This was impaired in hepatocytes of ZF rats on VAS, but partially recovered in those on VAD diet. In lean hepatocytes, the Pck1 expression was suppressed by insulin and induced by RA respectively. The insulin‐suppressed Pck1 expression was impaired in hepatocytes from ZF rats fed VAS diet and partially restored in that fed VAD diet. The RA‐induced Pck1 expression was normal in hepatocytes from ZF rats fed VAS, and was enhanced in that fed VAD. The Pklr expression was similar between ZL and ZF and not affected by VA status. We conclude that VA status modulate the insulin‐ and RA‐regulated hepatic gene expression in hepatocytes of ZF rats. It suggests that micronutrients contribute to the hepatic insulin response. Grant Funding Source : AHA