title: Lower mitochondrial proton leak and decreased glutathione redox in primary muscle cells of obese diet-resistant versus diet-sensitive humans.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Primary myotubes derived from muscle biopsies of individuals identified as ODS or ODR were studied.
  
  
  METHODS
  Compliant ODS and ODR females who completed in the Ottawa Hospital Weight Management Program and identified as ODS and ODR participated in this study.
  
  
  METHODS
  Eleven ODS and nine ODR weight-stable females matched for age, body mass, and body mass index participated in this study.
  
  
  METHODS
  Vastus lateralis muscle biopsies were obtained and processed for muscle satellite cell isolation.
  
  
  METHODS
  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.
authors.affiliation: Department of Biochemistry, Microbiology, and Immunology (A.B.T., R.Z., W.C., E.L.S., J.K.Q., M.-E.H.), Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5; Department of Pathology, Anatomy, and Cell Biology (E.L.S.), Thomas Jefferson University, Philadelphia, Pennsylvania 19107; Division of Cardiology (R.M.), University of Ottawa Heart Institute, Ottawa, Ontario Canada K1Y 4W7; Ottawa Hospital Weight Management Clinic (R.D.), Ottawa Hospital, Ottawa, Ontario, Canada K1Y 4E9.
authors.forename: A Brianne
authors.initials: AB
authors.lastname: Thrush
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: William
authors.initials: W
authors.lastname: Chen
authors.forename: Erin L
authors.initials: EL
authors.lastname: Seifert
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Quizi
authors.forename: Ruth
authors.initials: R
authors.lastname: McPherson
authors.forename: Robert
authors.initials: R
authors.lastname: Dent
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Harper
mesh_terms: D000328:Adult; D004032:Diet; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D005978:Glutathione