Mitochondrial respiration in subcutaneous and visceral adipose tissue from patients with morbid obesity.
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.
Kraunsøe
Regitze
R
Center for Healthy Ageing, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
Boushel
Robert
R
Hansen
Christina Neigaard
CN
Schjerling
Peter
P
Qvortrup
Klaus
K
Støckel
Mikael
M
Mikines
Kári J
KJ
Dela
Flemming
F
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
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