TitleDefects in mitochondrial efficiency and H2O2 emissions in obese women are restored to a lean phenotype with aerobic exercise training.
Publication TypeJournal Article
Year of Publication2015
AuthorsKonopka, AR, Asante, A, Lanza, IR, Robinson, MM, Johnson, ML, Man, CDalla, Cobelli, C, Amols, MH, Irving, BA, Nair, KS
Date Published2015 Jun
KeywordsEstradiol, Exercise, Female, Humans, Hydrogen Peroxide, Insulin Resistance, Mitochondria, Obesity, Oxidative Stress, Oxygen Consumption, Progesterone, Thinness

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.

Alternate JournalDiabetes
PubMed ID25605809
PubMed Central IDPMC4439568
Grant ListR01 DK041973 / DK / NIDDK NIH HHS / United States
UL1TR000135 / TR / NCATS NIH HHS / United States
KL2TR000136 / TR / NCATS NIH HHS / United States
T32DK007352 / DK / NIDDK NIH HHS / United States
KL2RR024151 / RR / NCRR NIH HHS / United States
KL2 TR000136 / TR / NCATS NIH HHS / United States
KL2 RR024151 / RR / NCRR NIH HHS / United States
U24 DK100469 / DK / NIDDK NIH HHS / United States
UL1 TR000135 / TR / NCATS NIH HHS / United States
DK41973 / DK / NIDDK NIH HHS / United States
T32 DK007352 / DK / NIDDK NIH HHS / United States
U24DK100469 / DK / NIDDK NIH HHS / United States
R56 DK041973 / DK / NIDDK NIH HHS / United States