Journal of Applied Physiology AJP: Renal Physiology
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J Appl Physiol 104: 708-715, 2008. First published December 13, 2007; doi:10.1152/japplphysiol.01034.2007
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Exercise-induced attenuation of obesity, hyperinsulinemia, and skeletal muscle lipid peroxidation in the OLETF rat

R. Tyler Morris,1 Matthew J. Laye,1 Simon J. Lees,5 R. Scott Rector,3 John P. Thyfault,2,3,4 and Frank W. Booth1,5,6

1Department of Medical Pharmacology and Physiology, School of Medicine; 2Harry S. Truman Memorial Veterans Medical Center; Departments of 3Internal Medicine and 4Nutritional Sciences; 5Department of Biomedical Sciences, College of Veterinary Medicine; and 6Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri

Submitted 27 September 2007 ; accepted in final form 12 December 2007

The Otsuka Long-Evans Tokushima fatty (OLETF) rat is a model of hyperphagic obesity in which the animals retain the desire to run voluntarily. Running wheels were provided for 4-wk-old OLETF rats for 16 wk before they were killed 5 h (WL5), 53 h (WL53), or 173 h (WL173) after the wheels were locked. Sedentary (SED) OLETF rats that were not given access to running wheels served as age-matched cohorts. Epididymal fat pad mass, adipocyte volume, and adipocyte number were 58%, 39%, and 47% less, respectively, in WL5 than SED rats. Contrary to cessation of daily running in Fischer 344 x Brown Norway rats, epididymal fat did not increase during the first 173 h of running cessation in the OLETF runners. Serum insulin and glucose levels were 77% and 29% less, respectively, in WL5 than SED rats. Oil red O staining for intramyocellular lipid accumulation was not statistically different among groups. However, lipid peroxidation levels, as determined by total trans-4-hydroxy-2-nonenal (4-HNE) and 4-HNE normalized to oil red O, was higher in epitrochlearis muscles of SED than WL5, WL53, and WL173 rats. mRNA levels of glutathione S-transferase-{alpha} type 4, an enzyme involved in cellular defense against electrophilic compounds such as 4-HNE, were higher in epitrochlearis muscle of WL53 than WL173 and SED rats. In contrast, 4-HNE levels in omental fat were unaltered. Epitrochlearis muscle palmitate oxidation and relative transcript levels for peroxisome proliferator-activated receptor-{delta} and peroxisome proliferator-activated receptor-{gamma} coactivator type 1 were surprisingly not different between runners and SED rats. In summary, voluntary running was associated with lower levels of lipid peroxidation in skeletal muscle without significant changes in intramyocellular lipids or mitochondrial markers in OLETF rats at 20 wk of age. Therefore, even in a genetic animal model of extreme overeating, daily physical activity promotes improved health of skeletal muscle.

physical activity; oxidative stress; chronic disease


Address for reprint requests and other correspondence: F. W. Booth, Univ. of Missouri, Dept. of Biomedical Sciences, 1600 E. Rollins, E102, Vet. Med. Bldg., Columbia, MO 65201 (e-mail: boothf{at}missouri.edu)




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