Lower mitochondrial proton leak and decreased glutathione redox in primary muscle cells of obese diet-resistant versus diet-sensitive humans

J Clin Endocrinol Metab. 2014 Nov;99(11):4223-30. doi: 10.1210/jc.2014-1726. Epub 2014 Aug 22.

Abstract

Context: Weight loss success in response to energy restriction is highly variable. This may be due in part to differences in mitochondrial function and oxidative stress.

Objective: The objective of the study was to determine whether mitochondrial function, content, and oxidative stress differ in well-matched obese individuals in the upper [obese diet sensitive (ODS)] vs lower quintiles [obese diet resistant (ODR)] for rate of weight loss.

Design: Primary myotubes derived from muscle biopsies of individuals identified as ODS or ODR were studied.

Setting: Compliant ODS and ODR females who completed in the Ottawa Hospital Weight Management Program and identified as ODS and ODR participated in this study.

Patients or other participants: Eleven ODS and nine ODR weight-stable females matched for age, body mass, and body mass index participated in this study.

Intervention: Vastus lateralis muscle biopsies were obtained and processed for muscle satellite cell isolation.

Main outcome measures: Mitochondrial respiration, content, reactive oxygen species, and glutathione redox ratios were measured in the myotubes of ODS and ODR individuals.

Results: Mitochondrial proton leak was increased in myotubes of ODS compared with ODR (P < .05). Reduced and oxidized glutathione was decreased in the myotubes of ODR vs ODS (P < .05), indicating a more oxidized glutathione redox state. There were no differences in myotube mitochondrial content, uncoupling protein 3, or adenine nucleotide translocase levels.

Conclusions: Lower rate of mitochondrial proton leak in muscle is a cell autonomous phenomenon in ODR vs ODS individuals, and this is associated with a more oxidized glutathione redox state in ODR vs ODS myotubes. The muscle of ODR subjects may thus have a lower capacity to adapt to oxidative stress as compared with ODS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Diet
  • Female
  • Glutathione / metabolism*
  • Humans
  • Male
  • Membrane Potential, Mitochondrial / physiology
  • Middle Aged
  • Mitochondria, Muscle / metabolism*
  • Muscle, Skeletal / metabolism*
  • Obesity / metabolism*
  • Oxidation-Reduction
  • Oxidative Stress / physiology*
  • Reactive Oxygen Species / metabolism
  • Satellite Cells, Skeletal Muscle / metabolism*

Substances

  • Reactive Oxygen Species
  • Glutathione