Increased lipid accumulation and insulin resistance in transgenic mice expressing DGAT2 in glycolytic (type II) muscle

Abstract

Insulin resistance and type 2 diabetes are frequently accompanied by lipid accumulation in skeletal muscle. However, it is unknown whether primary lipid deposition in skeletal muscle is sufficient to cause insulin resistance or whether the type of muscle fiber, oxidative or glycolytic fiber, is an important determinant of lipid-mediated insulin resistance. Here we utilized transgenic mice to test the hypothesis that lipid accumulation specifically in glycolytic muscle promotes insulin resistance. Overexpression of DGAT2, which encodes an acyl-CoA:diacylglycerol acyltransferase that catalyzes triacylglycerol (TG) synthesis, in glycolytic muscle of mice increased the content of TG, ceramides, ..