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°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 (GMOSD) and uncoupled respiration were significantly (P < 0.05) higher in visceral (0.95 ± 0.05 and 1.15 ± 0.06 pmol O2 s−1 mg−1, respectively) compared with subcutaneous (0.76 ± 0.04 and 0.98 ± 0.05 pmol O2 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.

[1]  R. Boushel,et al.  Regional anatomic differences in skeletal muscle mitochondrial respiration in type 2 diabetes and obesity. , 2010, The Journal of clinical endocrinology and metabolism.

[2]  Dorothy D. Sears,et al.  Mechanisms of human insulin resistance and thiazolidinedione-mediated insulin sensitization , 2009, Proceedings of the National Academy of Sciences.

[3]  E. Gnaiger.  Capacity of oxidative phosphorylation in human skeletal muscle: new perspectives of mitochondrial physiology. , 2009, The international journal of biochemistry & cell biology.

[4]  R. Boushel,et al.  Reduced skeletal muscle mitochondrial respiration and improved glucose metabolism in nondiabetic obese women during a very low calorie dietary intervention leading to rapid weight loss. , 2009, Metabolism: clinical and experimental.

[5]  I. Ara,et al.  Are substrate use during exercise and mitochondrial respiratory capacity decreased in arm and leg muscle in type 2 diabetes? , 2009, Diabetologia.

[6]  R. Boushel,et al.  Effect of hyperglycemia on mitochondrial respiration in type 2 diabetes. , 2009, The Journal of clinical endocrinology and metabolism.

[7]  T. Lehtimäki,et al.  Effects of weight loss on visceral and abdominal subcutaneous adipose tissue blood-flow and insulin-mediated glucose uptake in healthy obese subjects , 2009, Annals of medicine.

[8]  Joris Hoeks,et al.  Lower Intrinsic ADP-Stimulated Mitochondrial Respiration Underlies In Vivo Mitochondrial Dysfunction in Muscle of Male Type 2 Diabetic Patients , 2008, Diabetes.

[9]  Min-Seon Kim,et al.  Essential Role of Mitochondrial Function in Adiponectin Synthesis in Adipocytes , 2007, Diabetes.

[10]  P. Arner,et al.  Strong association between mitochondrial DNA copy number and lipogenesis in human white adipose tissue , 2007, Diabetologia.

[11]  K. Sahlin,et al.  Mitochondrial Respiration Is Decreased in Skeletal Muscle of Patients With Type 2 Diabetes , 2007, Diabetes.

[12]  R. Boushel,et al.  Patients with type 2 diabetes have normal mitochondrial function in skeletal muscle , 2007, Diabetologia.

[13]  R. Boushel,et al.  Mitochondrial oxidative function and type 2 diabetes. , 2006, Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme.

[14]  P. Arner,et al.  Downregulation of Electron Transport Chain Genes in Visceral Adipose Tissue in Type 2 Diabetes Independent of Obesity and Possibly Involving Tumor Necrosis Factor-α , 2006, Diabetes.

[15]  K. Petersen,et al.  Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. , 2005, The Journal of clinical investigation.

[16]  A. Vidal-Puig,et al.  Visfatin: the missing link between intra-abdominal obesity and diabetes? , 2005, Trends in molecular medicine.

[17]  K. Petersen,et al.  Mitochondrial dysfunction and type 2 diabetes , 2005, Current diabetes reports.

[18]  G. Bray,et al.  Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo. , 2005, Diabetes.

[19]  C. Homko,et al.  Thiazolidinediones upregulate fatty acid uptake and oxidation in adipose tissue of diabetic patients. , 2005, Diabetes.

[20]  M. Rigoulet,et al.  Regional differences in oxidative capacity of rat white adipose tissue are linked to the mitochondrial content of mature adipocytes , 2004, Molecular and Cellular Biochemistry.

[21]  M. Lazar,et al.  Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone. , 2004, The Journal of clinical investigation.

[22]  M. Daly,et al.  PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes , 2003, Nature Genetics.

[23]  A. Butte,et al.  Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1 , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[24]  Jing He,et al.  Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. , 2002, Diabetes.

[25]  Robert Ross,et al.  Abdominal adiposity and insulin resistance in obese men. , 2002, American journal of physiology. Endocrinology and metabolism.

[26]  Johan Auwerx,et al.  Depot-Specific Differences in Adipose Tissue Gene Expression in Lean and Obese Subjects , 1998, Diabetes.

[27]  L. Sjöström,et al.  The morphology and metabolism of intraabdominal adipose tissue in men. , 1992, Metabolism: clinical and experimental.

[28]  L. Sjöström,et al.  Measurements of adipose tissue respiration in a closed chamber using an oxygen sensor: methodological considerations. , 1986, Journal of lipid research.

[29]  L. Sjöström,et al.  Oxygen consumption in collagenase-liberated rat adipocytes in relation to cell size and age. , 1984, Metabolism: clinical and experimental.

[30]  H. Vernon.  THE SOLUBILITY OF AIR IN FATS AND ITS RELATION TO CAISSON DISEASE. , 1907 .

[31]  J. Holloszy.  Skeletal muscle "mitochondrial deficiency" does not mediate insulin resistance. , 2009, The American journal of clinical nutrition.

[32]  J. Hrebícek,et al.  Gender differences in tumor necrosis factor alpha and leptin secretion from subcutaneous and visceral fat tissue. , 2004, Physiological research.

[33]  S. O’Rahilly,et al.  Depot- and sex-specific differences in human leptin mRNA expression: implications for the control of regional fat distribution. , 1997, Diabetes.

[34]  M. Halperin,et al.  Transport of reduced nicotinamide-adenine dinucleotide into mitochondria of rat white adipose tissue. , 1970, The Biochemical journal.