title: Impaired mitochondrial oxidative phosphorylation and supercomplex assembly in rectus abdominis muscle of diabetic obese individuals.
abstract: OBJECTIVE
  Skeletal muscle mitochondrial dysfunction has been documented in patients with type 2 diabetes mellitus; however, specific respiratory defects and their mechanisms are poorly understood. The aim of the current study was to examine oxidative phosphorylation and electron transport chain (ETC) supercomplex assembly in rectus abdominis muscles of 10 obese diabetic and 10 obese non-diabetic individuals.
  
  
  METHODS
  Twenty obese women undergoing Roux-en-Y gastric bypass surgery were recruited for this study. Muscle samples were obtained intraoperatively and subdivided for multiple analyses, including high-resolution respirometry and assessment of supercomplex assembly. Clinical data obtained from referring physicians were correlated with laboratory findings.
  
  
  RESULTS
  Participants in both groups were of a similar age, weight and BMI. Mitochondrial respiration rates were markedly reduced in diabetic vs non-diabetic patients. This defect was observed during maximal ADP-stimulated respiration in the presence of complex I-linked substrates and complex I- and II-linked substrates, and during maximal uncoupled respiration. There were no differences in fatty acid (octanoyl carnitine) supported respiration, leak respiration or isolated activity of cytochrome c oxidase. Intriguingly, significant correlations were found between glycated haemoglobin (HbA1c) levels and maximal respiration or respiration supported by complex I, complex I and II or fatty acid. In the muscle of diabetic patients, blue native gel electrophoresis revealed a striking decrease in complex I, III and IV containing ETC supercomplexes.
  
  
  CONCLUSIONS
  These findings support the hypothesis that ETC supercomplex assembly may be an important underlying mechanism of muscle mitochondrial dysfunction in type 2 diabetes mellitus.
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, ON, Canada, K1H 8M5.
authors.forename: Ghadi
authors.initials: G
authors.lastname: Antoun
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, ON, Canada, K1H 8M5.
authors.forename: Fiona
authors.initials: F
authors.lastname: McMurray
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, ON, Canada, K1H 8M5.
authors.forename: A Brianne
authors.initials: AB
authors.lastname: Thrush
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Patten
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, ON, Canada, K1H 8M5.
authors.forename: Alyssa C
authors.initials: AC
authors.lastname: Peixoto
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
authors.forename: Ruth S
authors.initials: RS
authors.lastname: Slack
authors.affiliation: Atherogenomics Laboratory, University of Ottawa Heart Institute, Ottawa, ON, Canada.
authors.forename: Ruth
authors.initials: R
authors.lastname: McPherson
authors.affiliation: Ottawa Hospital Weight Management Clinic, The Ottawa Hospital, Ottawa, ON, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Dent
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Rd, Ottawa, ON, Canada, K1H 8M5. mharper@uottawa.ca.
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Harper
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism*; D042967:Electron Transport Complex I / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D017568:Rectus Abdominis / Q000378:metabolism*
chemical_list: D000244:Adenosine Diphosphate; D045222:Electron Transport Chain Complex Proteins; D042967:Electron Transport Complex I; D003576:Electron Transport Complex IV; D005227:Fatty Acids; D006442:Glycated Hemoglobin
keywords: Bioenergetics; Electron transport chain; Mitochondria; Obesity; Skeletal muscle; Type 2 diabetes mellitus