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 Sreekumaran Nair

Research output: Contribution to journalArticle

42 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2104-2115
Number of pages12
JournalDiabetes
Volume64
Issue number6
DOIs
StatePublished - Jun 1 2015

Fingerprint

Exercise
Phenotype
Meals
Insulin Resistance
Obesity
Insulin
Energy Metabolism
Fats
Polycystic Ovary Syndrome
Oxygen Consumption
Catalase
DNA Damage
Oxidation-Reduction
Mitochondria
Skeletal Muscle
Antioxidants
Phosphorylation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Defects in mitochondrial efficiency and H2O2 emissions in obese women are restored to a lean phenotype with aerobic exercise training. / Konopka, Adam R.; Asante, Albert; Lanza, Ian R; Robinson, Matthew M.; Johnson, Matthew L.; Dalla Man, Chiara; Cobelli, Claudio; Amols, Mark H.; Irving, Brian A.; Nair, K Sreekumaran.

In: Diabetes, Vol. 64, No. 6, 01.06.2015, p. 2104-2115.

Research output: Contribution to journalArticle

Konopka, AR, Asante, A, Lanza, IR, Robinson, MM, Johnson, ML, Dalla Man, C, Cobelli, C, Amols, MH, Irving, BA & Nair, KS 2015, 'Defects in mitochondrial efficiency and H2O2 emissions in obese women are restored to a lean phenotype with aerobic exercise training', Diabetes, vol. 64, no. 6, pp. 2104-2115. https://doi.org/10.2337/db14-1701
Konopka, Adam R. ; Asante, Albert ; Lanza, Ian R ; Robinson, Matthew M. ; Johnson, Matthew L. ; Dalla Man, Chiara ; Cobelli, Claudio ; Amols, Mark H. ; Irving, Brian A. ; Nair, K Sreekumaran. / Defects in mitochondrial efficiency and H2O2 emissions in obese women are restored to a lean phenotype with aerobic exercise training. In: Diabetes. 2015 ; Vol. 64, No. 6. pp. 2104-2115.
@article{10d205c75d4e48458d416f813f8ed47b,
title = "Defects in mitochondrial efficiency and H2O2 emissions in obese women are restored to a lean phenotype with aerobic exercise training",
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.",
author = "Konopka, {Adam R.} and Albert Asante and Lanza, {Ian R} and Robinson, {Matthew M.} and Johnson, {Matthew L.} and {Dalla Man}, Chiara and Claudio Cobelli and Amols, {Mark H.} and Irving, {Brian A.} and Nair, {K Sreekumaran}",
year = "2015",
month = "6",
day = "1",
doi = "10.2337/db14-1701",
language = "English (US)",
volume = "64",
pages = "2104--2115",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "6",

}

TY - JOUR

T1 - Defects in mitochondrial efficiency and H2O2 emissions in obese women are restored to a lean phenotype with aerobic exercise training

AU - Konopka, Adam R.

AU - Asante, Albert

AU - Lanza, Ian R

AU - Robinson, Matthew M.

AU - Johnson, Matthew L.

AU - Dalla Man, Chiara

AU - Cobelli, Claudio

AU - Amols, Mark H.

AU - Irving, Brian A.

AU - Nair, K Sreekumaran

PY - 2015/6/1

Y1 - 2015/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84942262554&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84942262554&partnerID=8YFLogxK

U2 - 10.2337/db14-1701

DO - 10.2337/db14-1701

M3 - Article

C2 - 25605809

AN - SCOPUS:84942262554

VL - 64

SP - 2104

EP - 2115

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 6

ER -