Intracellular fatty acid metabolism in skeletal muscle and insulin resistance

• Published in: Current diabetes reviews Vol. 1; no. 3; p. 331
• Main Authors: Koh, Eun H, Lee, Woo J, Kim, Min-Seon, Park, Joong-Yeol, Lee, In K, Lee, Ki-Up
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.11.2005
• Subjects: Adenylate Kinase - metabolism; Animals; Fatty Acids - metabolism; Glucose - metabolism; Glycolysis; Homeostasis; Humans; Insulin Resistance - physiology; Mitochondria, Muscle - metabolism; Muscle, Skeletal - metabolism; Muscle, Skeletal - physiology
• ISSN: 1875-6417
• DOI: 10.2174/157339905774574347

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 glucose-fatty 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 PPARalpha activator), rosiglitazone (a PPARgamma 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.