Differential effects of caloric intake and vitamin A status on insulin‐regulated Pck1 and Srebp1c expression in hepatocytes from Zucker fatty rats

Abstract

Insulin‐regulated hepatic gene expression is impaired in Zucker fatty (ZF) rats. This is corrected by fasting or introducing vitamin A (VA) deficiency. VA deficiency reduces VA status and caloric intake. To separate these two effects, the insulin‐regulated Pck1 and Srebp1c expression were analyzed in primary hepatocytes from ZF rats. ZF rats after weaning were fed ad libitum a VA deficient (VAD), an isocaloric VA sufficient (VAS) diet ad libitum or the same amount of VAS diet consumed by the VAD group in the previous day for 8 weeks. The Pck1 and Srebp1c mRNA levels after insulin stimulation for 6 hours in the primary hepatocytes of these rats were determined by real‐time PCR. In hepatocytes of ZF rats fed the VAS diet, the insulin‐mediated inhibition of Pck1 and induction of Srebp1c expressions were impaired. This impairment was partially restored in hepatocytes of ZF rats fed the VAD diet. In hepatocytes of ZF rats pair‐fed the VAS diet, the insulin‐inhibited Pck1 expression, but not insulin‐induced Srebp1c expression, returned to normal. We conclude that insulin‐regulated expressions of Pck1 and Srebp1c in the ZF rat hepatocytes are respectively affected by caloric intake and VA status of the rats.Grant Funding Source: AHA (09SDG2140003)