Vitamin A and feeding statuses modulate the insulin‐regulated Pck1 and Srebp‐1c expression in primary hepatocytes from lean and obese rats (645.1)

Abstract

The hepatic insulin resistance occurs with profound changes of the expression of genes for glucose and lipid metabolism. Previously, we compared insulin‐regulated gene expression in hepatocytes of Zucker lean (ZL) and fatty (ZF) rats. We found that insulin‐regulated Srebp‐1c and Pck1 expressions are impaired in hepatocytes of ZF, but not ZL, rats fed ad libitum, which can be corrected by fasting. As vitamin A (VA) deficiency causes reduction of body mass and food intake in rats, we set up a pair‐feeding experiment to study the effects of energy intake and VA status on the insulin‐regulated gene expression. Rats were fed a VA deficient (VAD) diet ad libitum (VAD‐AD) for 8 weeks. An isocaloric VA sufficient (VAS) diet equal to the amount of the VAD diet taken by the VAD‐AD rat in 24‐hour was given to the pair‐fed rats in two ways. On the last day, VAS‐PF‐AD rat was allowed to ingest the VAS diet ad libitum to avoid the fasting state. VAS‐PF‐4M rat was given one fourth of the daily ration every 6 hours. Here, we report that the insulin‐ and retinoic acid (RA)‐regulated Srebp1c and Pck1 expressions were impaired in hepatocytes of ZF rats fed ad libitum, confirming our previous results. The impairment was partially corrected in hepatocytes of ZF rats fed the VAD diet ad libitum. The ZL and ZF VAS‐PF‐AD or ‐4M rats had higher body mass and feed efficiency than their VAD‐AD controls before the reduction of food intake occurred. The VAS‐PF rats overate when enough diet was present at the end of the pair‐feeding paradigm. Insulin‐inhibited Pck1 (VAS‐PF‐AD ZL rats) and induced Srebp1c (VAS‐PF‐AD ZL and ZF rats) expressions ware partially impaired. The expressions of genes for hepatic VA metabolism were altered in those rats. VA and feeding statuses modulate the insulin‐regulated gene expression.Grant Funding Source: Supported by AHA