The effect of high ‐fat diet and inhibition of ceramide production on insulin action in liver

Hepatic insulin resistance induced by high ‐fat diet resulted from an increase in synthesis rate of ceramide and diacylglycerol (DAG). Myriocin treatment improved insulin sensitivity, which was accompanied by a decrease in the synthesis rate and content of ceramide and DAG. Liver, as one of the most important organs involved in lipids and glucose metabolism, is perceived as a key tissue for pharmacotherapy of insulin resistance (IRes) and type 2 diabetes. Ceramides (Cer) are biologically active lipids, which accumulation is associated with the induction of muscle IRes. We sought to determine the role of intrahepatic bioactive lipids production on insulin action in liver of insulin ‐resistant rats and after myriocin administration. The experiments were conducted on male Wistar rats divided into three groups: Control, fed high‐fat diet (HFD), and fed HFD and treated with myriocin (HFD/Myr). Before sacrifice, the animals were infused with a [U‐13C]palmitate to calculate lipid synthesis rate by means of tracer incorporation technique in particular lipid groups. Liver Cer, diacylglycerols (DAG), acyl ‐carnitine concentration, and isotopic enrichment were analyzed by LC/MS/MS. Proteins involved in lipid metabolism and insulin pathway were analyzed by western blot analysis. An OGTT and ITT was also performed. HFD‐induced IRes and increased both the synthesis rate and the content of DAG and Cer , which was accompanied by inhibition of an insulin pathway. Interestingly, my...
Source: Journal of Cellular Physiology - Category: Cytology Authors: Tags: ORIGINAL RESEARCH ARTICLE Source Type: research