Artificial selection for high-capacity endurance running is protective against high-fat diet-induced insulin resistance

Departments of 1 Physiology, 3 Exercise and Sport Science, and 5 Anatomy and Cell Biology, East Carolina University, Greenville, North Carolina; 2 Departments of Nutritional Sciences and Internal Medicine, and Harry S. Truman Veterans Affairs Hospital, University of Missouri, Columbia, Missouri; and 4 Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, Michigan Submitted 14 September 2006 ; accepted in final form 21 February 2007 Elevated oxidative capacity, such as occurs via endurance exercise training, is believed to protect against the development of obesity and diabetes. Rats bred both for low (LCR)- and high (HCR)-capacity endurance running provide a genetic model with inherent differences in aerobic capacity that allows for the testing of this supposition without the confounding effects of a training stimulus. The purpose of this investigation was to determine the effects of a high-fat diet (HFD) on weight gain patterns, insulin sensitivity, and fatty acid oxidative capacity in LCR and HCR male rats in the untrained state. Results indicate chow-fed LCR rats were heavier, hypertriglyceridemic, less insulin sensitive, and had lower skeletal muscle oxidative capacity compared with HCR rats. Upon exposure to an HFD, LCR rats gained more weight and fat mass, and their insulin resistant condition was exacerbated, despite consuming similar amounts of metabolizable energy as chow-fed controls. These metabolic variables remained unaltered in HCR rats. The HFD increased skeletal muscle oxidative capacity similarly in both strains, whereas hepatic oxidative capacity was diminished only in LCR rats. These results suggest that LCR rats are predisposed to obesity and that expansion of skeletal muscle oxidative capacity does not prevent excess weight gain or the exacerbation of insulin resistance on an HFD. Elevated basal skeletal muscle oxidative capacity and the ability to preserve liver oxidative capacity may protect HCR rats from HFD-induced obesity and insulin resistance. fatty acid; lipid metabolism; liver; heart; skeletal muscle Address for reprint requests and other correspondence: R. M. Lust, Brody School of Medicine, 600 Moye Blvd., 6N-96 Brody Bldg., East Carolina Univ., Greenville, NC 27834 (e-mail: lustr{at}ecu.edu )