title: Mitochondrial respiration in subcutaneous and visceral adipose tissue from patients with morbid obesity.
abstract: Adipose tissue exerts important endocrine and metabolic functions in health and disease. Yet the bioenergetics of this tissue is not characterized in humans and possible regional differences are not elucidated. Using high resolution respirometry, mitochondrial respiration was quantified in human abdominal subcutaneous and intra-abdominal visceral (omentum majus) adipose tissue from biopsies obtained in 20 obese patients undergoing bariatric surgery. Mitochondrial DNA (mtDNA) and genomic DNA (gDNA) were determined by the PCR technique for estimation of mitochondrial density. Adipose tissue samples were permeabilized and respirometric measurements were performed in duplicate at 37 degrees C. Substrates (glutamate (G) + malate (M) + octanoyl carnitine (O) + succinate (S)) were added sequentially to provide electrons to complex I + II. ADP ((D)) for state 3 respiration was added after GM. Uncoupled respiration was measured after addition of FCCP. Visceral fat contained more mitochondria per milligram of tissue than subcutaneous fat, but the cells were smaller. Robust, stable oxygen fluxes were found in both tissues, and coupled state 3 (GMOS(D)) and uncoupled respiration were significantly (P < 0.05) higher in visceral (0.95 +/- 0.05 and 1.15 +/- 0.06 pmol O(2) s(1) mg(1), respectively) compared with subcutaneous (0.76 +/- 0.04 and 0.98 +/- 0.05 pmol O(2) s(1) mg(1), respectively) adipose tissue. Expressed per mtDNA, visceral adipose tissue had significantly (P < 0.05) lower mitochondrial respiration. Substrate control ratios were higher and uncoupling control ratio lower (P < 0.05) in visceral compared with subcutaneous adipose tissue. We conclude that visceral fat is bioenergetically more active and more sensitive to mitochondrial substrate supply than subcutaneous fat. Oxidative phosphorylation has a higher relative activity in visceral compared with subcutaneous adipose tissue.
authors.affiliation: Center for Healthy Ageing, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Regitze
authors.initials: R
authors.lastname: Kraunsøe
authors.forename: Robert
authors.initials: R
authors.lastname: Boushel
authors.forename: Christina Neigaard
authors.initials: CN
authors.lastname: Hansen
authors.forename: Peter
authors.initials: P
authors.lastname: Schjerling
authors.forename: Klaus
authors.initials: K
authors.lastname: Qvortrup
authors.forename: Mikael
authors.initials: M
authors.lastname: Støckel
authors.forename: Kári J
authors.initials: KJ
authors.lastname: Mikines
authors.forename: Flemming
authors.initials: F
authors.lastname: Dela
mesh_terms: D000328:Adult; D001706:Biopsy; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002331:Carnitine / Q000031:analogs & derivatives / Q000378:metabolism; D019069:Cell Respiration / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008293:Malates / Q000378:metabolism; D008297:Male; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009767:Obesity, Morbid / Q000378:metabolism* / Q000473:pathology; D009852:Omentum; D010085:Oxidative Phosphorylation; D050507:Subcutaneous Fat, Abdominal / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D019802:Succinic Acid / Q000378:metabolism; D013997:Time Factors; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D004272:DNA, Mitochondrial; D008293:Malates; D014475:Uncoupling Agents; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D018698:Glutamic Acid; C030298:malic acid; D019802:Succinic Acid; C008698:octanoylcarnitine; D002331:Carnitine