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Am J Physiol Endocrinol Metab (March 4, 2008). doi:10.1152/ajpendo.00769.2007
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Submitted on December 11, 2007
Accepted on February 14, 2008

Exercise-induced Alterations in Intramyocellular Lipids and Insulin Resistance: The Athlete’s Paradox Revisited

John J Dube1, Francesca Amati2, Maja Stefanovic-Racic2, Frederico Toledo3, Sarah E Sauers2, and Bret H. Goodpaster4*

1 Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, Pennsylvania, United States; , United States
2 Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
3 Medicine / Division of Endocrinolgy, University of Pittsburgh, Pittsburgh, Pennsylvania, United States; Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
4 Division of Endocrinology and Metabolism, University of Pittsburgh Department of Medicine, Pittsburgh, Pennsylvania, United States

* To whom correspondence should be addressed. E-mail: goodpaster{at}dom.pitt.edu.

We previously reported an "athlete’s paradox" in which endurance-trained athletes, who possess a high oxidative capacity and enhanced insulin sensitivity, also have higher intramyocellular lipid (IMCL) content. The purpose of this study was to determine whether moderate exercise training would increase IMCL, oxidative capacity of muscle and insulin sensitivity in previously sedentary overweight to obese, insulin resistant older subjects. Twenty-five older (66.4±0.8years) obese (BMI=30.3±0.7kg/m2) men (n=9) and women (n=16) completed a 16-week moderate but progressive exercise training program. Body weight and fat mass modestly but significantly (P<0.01) decreased. Insulin sensitivity, measured using the euglycemic-hyperinsulinemic clamp, was increased (21%, P=0.02) with modest improvements (7%, P=0.04) in aerobic fitness (VO2peak). Histochemical analyses of IMCL (Oil Red O staining), oxidative capacity (succinate dehydrogenase activity; SDH), glycogen content, capillary density and fiber type were performed on skeletal muscle biopsies. Exercise training increased IMCL by 21%. In contrast, diacylglycerol and ceramide, measure by mass-spectroscopy, were decreased (n=13, -29% and -24%, respectively,both P<0.05) with exercise training. SDH (19%), glycogen content (15%), capillary density (7%) and the percentage of type I, slow-oxidative fibers (from 50.8% to 55.7%), all P≤0.05 were increased after exercise. In summary, these results extend the "athlete’s paradox" by demonstrating that chronic exercise in overweight to obese older adults improves insulin sensitivity in conjunction with favorable alterations in lipid partitioning and an enhanced oxidative capacity within muscle. Therefore, several key deleterious effects of aging and/or obesity on the metabolic profile of skeletal muscle can be reversed with only moderate increases in physical activity.




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F. Amati, J. J. Dube, C. Shay, and B. H. Goodpaster
Separate and combined effects of exercise training and weight loss on exercise efficiency and substrate oxidation
J Appl Physiol, September 1, 2008; 105(3): 825 - 831.
[Abstract] [Full Text] [PDF]




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