Abstract
Unattended hepatic insulin resistance predisposes individuals to dyslipidemia, type 2 diabetes and many other metabolic complications. The mechanism of hepatic insulin resistance at the gene expression level remains unrevealed. To examine the effects of vitamin A (VA), total energy intake and feeding conditions on the insulin-regulated gene expression in primary hepatocytes of Zucker lean (ZL) and fatty (ZF) rats, we analyze the expression levels of hepatic model genes in response to the treatments of insulin and retinoic acid (RA). We report that the insulin- and RA-regulated glucokinase, sterol regulatory element-binding protein-1c and cytosolic form of phosphoenolpyruvate carboxykinase expressions are impaired in hepatocytes of ZF rats fed chow or a VA sufficient (VAS) diet ad libitum. The impairments are partially corrected when ZF rats are fed a VA deficient (VAD) diet ad libitum or pair-fed a VAS diet to the intake of their VAD counterparts in non-fasting conditions. Interestingly in the pair-fed ZL and ZF rats, transient overeating on the last day of pair-feeding regimen changes the expression levels of some VA catabolic genes, and impairs the insulin- and RA-regulated gene expression in hepatocytes. These results demonstrate that VA and feeding statuses modulate the hepatic insulin sensitivity at the gene expression level.
Highlights
The liver is critical for glucose and lipid homeostasis, which is achieved partially through the regulation of hepatic gene expression in response to hormonal and nutritional stimuli [1,2]
The insulin- and retinoic acid (RA)-regulated Gck, Pck1, and Srebp-1c expressions were impaired in primary hepatocytes from Zucker fatty (ZF) rats fed chow ad libitum
The expressions of liver type pyruvate kinase gene (Pklr) in primary hepatocytes from either Zucker lean (ZL) or ZF rats were not affected by insulin and RA treatments (Figure 1D)
Summary
The liver is critical for glucose and lipid homeostasis, which is achieved partially through the regulation of hepatic gene expression in response to hormonal and nutritional stimuli [1,2]. The disturbance of these responses may lead to the development of metabolic diseases, including obesity and type 2 diabetes [1]. It is able to concurrently induce the expression of lipogenic genes [2]. This phenomenon demonstrates the coexistence of hyperglycemia and hyperlipidemia in type 2 diabetes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
