Journal of Obesity & Weight Loss Therapy
Open Access

Abstract

Pathological elevation of plasma free fatty acids (FFAs) induces insulin resistance (IR). Previous work demonstrates that palmitic acid (PA) affects ectopic lipid distribution, which is associated with endoplasmic reticulum (ER) stress and IR, is rescued by oleic acid (OA). The exact mechanisms how different saturation FFAs regulate insulin signaling are poorly understood, especially in skeletal muscle where most of the blood glucose is consumed. We investigated the potential role of PA and OA in the lipid metabolism and insulin signal in C2C12 cells (mouse myoblast cell line). We found that diacylglycerol (DAG) was accumulated significantly in PA treatment with a time- and dose-dependent manner, suggesting that triacylglycerol (TAG) synthesis was blocked in the step of DAG to TAG. Overexpression of DAG acyltransferase 1 (DGAT1) efficiently converted DAG to TAG but overexpression of DGAT2 had almost no effect. In addition, PA-reduced phosphorylation of AKT was rescued by DGAT1 overexpression without affecting splicing of XBP-1 and phosphorylation of PERK. The data indicate that PA incorporation into non-toxic TAG was stopped at toxic DAG and DGAT1 could reduce PA-induced IR without rescuing PA-induced ER stress.

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