Diabetes 2015-06-01

Defects in mitochondrial efficiency and H2O2 emissions in obese women are restored to a lean phenotype with aerobic exercise training.

Adam R Konopka, Albert Asante, Ian R Lanza, Matthew M Robinson, Matthew L Johnson, Chiara Dalla Man, Claudio Cobelli, Mark H Amols, Brian A Irving, K S Nair

Index: Diabetes 64 , 2104-15, (2015)

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Abstract

The notion that mitochondria contribute to obesity-induced insulin resistance is highly debated. Therefore, we determined whether obese (BMI 33 kg/m(2)), insulin-resistant women with polycystic ovary syndrome had aberrant skeletal muscle mitochondrial physiology compared with lean, insulin-sensitive women (BMI 23 kg/m(2)). Maximal whole-body and mitochondrial oxygen consumption were not different between obese and lean women. However, obese women exhibited lower mitochondrial coupling and phosphorylation efficiency and elevated mitochondrial H2O2 (mtH2O2) emissions compared with lean women. We further evaluated the impact of 12 weeks of aerobic exercise on obesity-related impairments in insulin sensitivity and mitochondrial energetics in the fasted state and after a high-fat mixed meal. Exercise training reversed obesity-related mitochondrial derangements as evidenced by enhanced mitochondrial bioenergetics efficiency and decreased mtH2O2 production. A concomitant increase in catalase antioxidant activity and decreased DNA oxidative damage indicate improved cellular redox status and a potential mechanism contributing to improved insulin sensitivity. mtH2O2 emissions were refractory to a high-fat meal at baseline, but after exercise, mtH2O2 emissions increased after the meal, which resembles previous findings in lean individuals. We demonstrate that obese women exhibit impaired mitochondrial bioenergetics in the form of decreased efficiency and impaired mtH2O2 emissions, while exercise effectively restores mitochondrial physiology toward that of lean, insulin-sensitive individuals.© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.