Rat Liver HFD vs Chow, HFD vs PKCepsilon ASO

Insulin resistance drives the development of type 2 diabetes (T2D). In liver, diacylglycerol (DAG) is a key mediator of lipid-induced insulin resistance. DAG activates protein kinase C epsilon (PKCε), which phosphorylates and inhibits the insulin receptor. In rats, a 3-day high fat diet produces hepatic insulin resistance through this mechanism, and knockdown of hepatic PKCε protects against high fat diet-induced hepatic insulin resistance. Here we employ a systems level approach to uncover additional signaling pathways involved in high fat diet-induced hepatic insulin resistance. We used quantitative phosphoproteomics to map global in vivo changes in hepatic protein phosphorylation in chow-fed, high fat-fed, and high fat-fed with PKCε knockdown rats to distinguish the impact of lipid- and PKCε-induced protein phosphorylation.