An oversupply of fatty acids plays a key role in the development of insulin resistance in the skeletal muscle of obese individuals. Two related studies appearing online in advance of publication in the June print issue of the Journal of Clinical Investigation show that exercise and expression of the enzyme diacylglycerol acyltransferase 1 (DGAT1) have important effects on the development of insulin resistance. In the first of these two studies, Simon Schenk and Jeffrey Horowitz from the University of Michigan have shown that a single session of endurance exercise on a treadmill was sufficient to prevent insulin resistance in healthy, non-obese women. The authors showed that exercise triggered a corresponding increase in triglyceride synthesis within skeletal muscle as well as a parallel increase in the expression of the enzymes DGAT1 and mitochondrial glycerol-3-phosphate acyltransferase (mGPAT). By directing more fatty acids towards triglyceride synthesis within muscle, toxic fatty acid metabolite accumulation was reduced, which protected against fatty acid-induced insulin resistance. The study suggests that regularly performed endurance exercise may help improve insulin resistance in people with excess levels of available fatty acid, such as those with obesity. In a related study, Yi-Hao Yu and colleagues from Columbia University also observed an increase in DGAT1 activity in skeletal muscle and that fatty acids were channeled into triglycerides following exercise. In addition, the author studied mice that overexpressed DGAT1 in skeletal muscle and found that they were protected against high-fat diet-induced insulin resistance. The data illustrate how exercise can enhance muscle insulin sensitivity and the authors suggest that increasing muscle DGAT activity may offer a potential new approach to prevent and treat insulin resistance in type 2 diabetes. TITLE: Acute exercise increases triglyceride synthesis in skeletal muscle and prevents fatty acid-induced insulin resistance AUTHOR CONTACT: Jeffrey F. Horowitz University of Michigan, Ann Arbor, Michigan, USA RELATED ARTICLE: TITLE: Upregulation of myocellular DGAT1 augments triglyceride synthesis in skeletal muscle and protects against fat-induced insulin resistance AUTHOR CONTACT: Yi-Hao Yu Columbia University, New York, New York, USA ### JCI table of contents -- May 17, 2007 Contact: Brooke Grindlinger