Hepatic steatosis by dietary-conjugated linoleic acid is accompanied by accumulation of diacylglycerol and increased membrane-associated protein kinase C ε in mice

Abstract

Scope: Conjugated linoleic acid reduces weight gain and adipose mass while inducing liver enlargement, hepatic steatosis, and insulin resistance in mice. The objective of this study was to determine if hepatic steatosis induced by conjugated linoleic acid would predict for hepatic diacylglycerol accumulation, increased membrane-associated protein kinase C ε, and hyperglycemia.

Methods and results: Six-wk-old C57Bl/6 male mice were fed a high-saturated fat diet for 3 wk and were then randomized to high-saturated fat diet with or without conjugated linoleic acid (1.5% wt). Following a 6-wk intervention, hepatic triacylglycerol, diacylglycerol, membrane-associated protein kinase C ε, and gluconeogenic gene expression were determined. Fasting glucose was determined at baseline and at the end of the study. Conjugated linoleic acid increased hepatic triacylglycerol and diacylglycerol concentration in association with increased membrane-associated protein kinase C ε. Diacylglycerol concentration proved to be a better predictor than triacylglycerol concentration for the change from baseline in fasting glucose concentration and final insulin concentration. The increase in diacylglycerol concentration was also associated with increased hepatic gluconeogenic gene expression in conjugated linoleic acid-treated animals.

Conclusion: Our data suggest that conjugated linoleic acid can initiate the pathophysiology responsible for hepatic insulin resistance. Additional studies are needed to determine if the accumulation of hepatic diacylglycerol by conjugated linoleic acid leads to hepatic insulin resistance.