Abstract
Triglyceride accumulation in skeletal muscle is increased in subjects with insulin resistance. Increased intracellular lipolysis from stored triglyceride may induce insulin resistance in skeletal muscle by activating the glucosefatty acid cycle. However, inconsistent with this hypothesis, intracellular lipolysis from skeletal muscle is decreased in high fat-fed, insulin resistant rats. Therefore, it is suggested that an increase in triglyceride accumulation is the result of decreased mitochondrial fatty acid oxidation in the cells. As evidence, fenofibrate (a PPARα activator), rosiglitazone (a PPARγ activator) and alpha-lipoic acid completely prevented the development of diabetes in obese diabetes-prone rats. All three drugs increased fatty acid oxidation and decreased triglyceride accumulation in skeletal muscle. Administration of ALA activated AMPK and increased fatty acid oxidation. It is suggested that decreased fatty acid oxidation in skeletal muscle is one of the major factors leading to an accumulation of lipid metabolites and insulin resistance.
Keywords: triglyceride, fatty acid oxidation, mitochondria, insulin resistance, skeletal muscle, ampk
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