Obesity Surgery

, Volume 20, Issue 1, pp 84–92

Mitochondrial DNA Content in Human Omental Adipose Tissue

  • Andrea Lindinger
  • Ralph Peterli
  • Thomas Peters
  • Beatrice Kern
  • Markus von Flüe
  • Martine Calame
  • Matthias Hoch
  • Alex N. Eberle
  • Peter W. Lindinger
Clinical Research

Abstract

Background

Impairment of mitochondrial function plays an important role in obesity and the development of insulin resistance. The aim of this project was to investigate the mitochondrial DNA copy number in human omental adipose tissue with respect to obesity.

Methods

The mitochondrial DNA (mtDNA) content per single adipocyte derived from abdominal omental adipose tissue was determined by quantitative RT-PCR in a group of 75 patients, consisting of obese and morbidly obese subjects, as well as non-obese controls. Additionally, basal metabolic rate and fat oxidation rate were recorded and expressed as total values or per kilogram fat mass.

Results

MtDNA content is associated with obesity. Higher body mass index (BMI) resulted in a significantly elevated mtDNA count (ratio = 1.56; p = 0.0331) comparing non-obese (BMI < 30) to obese volunteers (BMI ≥ 30). The mtDNA count per cell was not correlated with age or gender. Diabetic patients showed a trend toward reduced mtDNA content. A seasonal change in mtDNA copy number could not be identified. In addition, a substudy investigating the basal metabolic rate and the fasting fat oxidation did not reveal any associations to the mtDNA count.

Conclusions

The mtDNA content per cell of omental adipose tissue did not correlate with various clinical parameters but tended to be reduced in patients with diabetes, which may partly explain the impairment of mitochondrial function observed in insulin resistance. Furthermore, the mtDNA content was significantly increased in patients suffering from obesity (BMI above 30). This might reflect a compensatory response to the development of obesity, which is associated with impairment of mitochondrial function.

Keywords

Obesity Omental adipose tissue Mitochondrial DNA content Adipocytes Diabetes 

References

  1. 1.
    Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004;84:277–359.CrossRefPubMedGoogle Scholar
  2. 2.
    Diamond F. The endocrine function of adipose tissue. Growth Genet Horm. 2002;18(2):17–22.Google Scholar
  3. 3.
    Trayhurn P. Adipocyte biology. Obes Rev. 2007;8(Suppl. 1):41–4.CrossRefPubMedGoogle Scholar
  4. 4.
    Maassen JA. Mitochondrial dysfunction in adipocytes: the culprit in type 2 diabetes? Diabetologia. 2006;49(4):619–20.CrossRefPubMedGoogle Scholar
  5. 5.
    Choo HJ, Kim JH, Kwon OB, et al. Mitochondria are impaired in the adipocytes of type 2 diabetic mice. Diabetologia. 2006;49:784–91.CrossRefPubMedGoogle Scholar
  6. 6.
    Guilherme A, Virbasius JV, Czech MP, et al. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol. 2008;9:367–77.CrossRefPubMedGoogle Scholar
  7. 7.
    Petersen KF, Befroy D, Shulman GI, et al. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science. 2003;500(5622):1140–2.CrossRefGoogle Scholar
  8. 8.
    Civitarese AE, Ravussin E. Minireview: mitochondrial energetics and insulin resistance. Endocrinology. 2007;149(3):950–4.CrossRefGoogle Scholar
  9. 9.
    Ernster L, Schatz G. Mitochondria: a historical review. J Cell Biol. 1981;91(3):227s–55.CrossRefPubMedGoogle Scholar
  10. 10.
    Kuroshima A. Brown adipose tissue thermogenesis as a physiological strategy for adaptation. Jpn J Physiol. 1993;43(43):117.CrossRefPubMedGoogle Scholar
  11. 11.
    Justo R, Oliver J, Gianotti M. Brown adipose tissue mitochondrial subpopulations show different morphological and thermogenic characteristics. Mitochondrion. 2005;5(1):45–53.CrossRefPubMedGoogle Scholar
  12. 12.
    Collins TJ, Bootman MD. Mitochondria are morphologically heterogenous within cells. J Exp Biol. 2003;206:1993–2000.CrossRefPubMedGoogle Scholar
  13. 13.
    Menziens RA, Gold PH. The turnover of mitochondria in a variety of tissues of young adult and aged rats. J Biol Chem. 1970;246(8):2425–9.Google Scholar
  14. 14.
    Masuyama M, Iida R, Matsuki T, et al. Quantitative change in mitochondrial DNA content in various mouse tissues during aging. Biochim Biophys Acta. 2005;1723:302–8.PubMedGoogle Scholar
  15. 15.
    Kelly DP, Scarpulla RC. Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev. 2004;18:357–68.CrossRefPubMedGoogle Scholar
  16. 16.
    Wu Z, Puigserver P, Spiegelman BM, et al. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell. 1999;98:115–24.CrossRefPubMedGoogle Scholar
  17. 17.
    van Marken Lichtenbelt WD, Vanhommering JW, Jaap Teule GJ, et al. Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009;360:1500–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Chan DC. Mitochondrial fusion and fission in mammals. Ann Rev Cell Dev Biol. 2006;22:79–99.CrossRefGoogle Scholar
  19. 19.
    Detmer SA, Chan DC. Functions and dysfunctions of mitochondrial dynamics. Nat Rev Mol Cell Biol. 2007;8:870–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Mingrone G, Manco M, Zorzano A, et al. Could the low level of expression of the gene encoding skeletal muscle mitofusin-2 account for the metabolic inflexibility of obesity? Diabetologia. 2005;48:2108–14.CrossRefPubMedGoogle Scholar
  21. 21.
    Bach D, Pich S, Zorzano A, et al. Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. J Biol Chem. 2003;278(19):17190–7.CrossRefPubMedGoogle Scholar
  22. 22.
    Wilson-Fritch L, Nicoloro S, Corvera S, et al. Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone. J Clin Invest. 2004;114(9):1281–9.PubMedGoogle Scholar
  23. 23.
    Peterli R, Wöllnerhanssen B, von Flüe M, et al. Prospective study of a two-stage operative concept in the treatment of morbid obesity: primary Lap-Band followed if needed by sleeve gastroectomy with duodenal switch. Obes Surg. 2007;17:334–40.CrossRefPubMedGoogle Scholar
  24. 24.
    Woelnerhanssen B, Kern B, Peterli R, et al. Predictors of outcome in treatment of morbid obesity by laparoscopic adjustable gastric banding: results of a prospective study of 380 patients. Surgery of Obesity and Related Disease. 2008;4:500–6.CrossRefGoogle Scholar
  25. 25.
    Bogacka I, Xie H, Smith SR, et al. Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo. Diabetes. 2005;54:1392–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Pinheiro JC, Bates DM. Mixed-effects models in S and S-PLUS. Springer: New York; 2000.Google Scholar
  27. 27.
    Barazzoni R, Short KR, Sreekumaran Nair K. Effects of aging on mitochondrial DNA copy number and cytochrome c oxidase gene expression in rat skeletal muscle, liver, and heart. JBC. 2000;275(5):3343–7.CrossRefGoogle Scholar
  28. 28.
    Colom B, Alcolea MP, Garcia-Palmer FJ, et al. Skeletal muscle of female rats exhibit higher mitochondrial mass and oxidative-phosphorylative capacities compared to males. Cell Physiol Biochem. 2007;19:205–12.CrossRefPubMedGoogle Scholar
  29. 29.
    Mollica MP, Lionetti L, Iossa S, et al. Cold exposure differently influences mitochondrial energy efficiacy in rat liver and skeletal muscle. FEBS Lett. 2005;579:1978–82.CrossRefPubMedGoogle Scholar
  30. 30.
    Needergard J, Bengtssen T. Unexpected evidence of brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab. 2007;293:E444–52.CrossRefGoogle Scholar
  31. 31.
    Wajchenberg BL. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev. 2000;21(6):697–738.CrossRefPubMedGoogle Scholar
  32. 32.
    Maassen JA. Mitochondrial diabetes: pathophysiology, clinical presentation, and genetic analysis. Am J Med Gen (Semin. Med. Genet.). 2002;115:66–70.CrossRefGoogle Scholar
  33. 33.
    Marcuello A, González-Alonso J, Díez-Sánchez C, et al. Skeletal muscle mitochondrial DNA content in exercising humans. J Appl Physiol. 2005;99:1372–7.CrossRefPubMedGoogle Scholar
  34. 34.
    Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell. 2005;120:483–95.CrossRefPubMedGoogle Scholar
  35. 35.
    Kaaman M, Sparks LM, Arner P, et al. Strong association between mitochondrial DNA copy number and lipogenesis in human white adipose tissue. Diabetologia. 2007;50:2526–33.CrossRefPubMedGoogle Scholar
  36. 36.
    Miller FJ, Rosenfeldt FL, Nagley P, et al. Precise determination of mitochondrial DNA copy number in human skeletal and cardiac muscle by a PCR-based assay: lack of changes of copy number with age. Nucleic Acids Res. 2003;31(11):e61.CrossRefPubMedGoogle Scholar
  37. 37.
    Rajala MW, Scherer PE. Minireview: the adipocyte—at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology. 2003;144(9):3765–73.CrossRefPubMedGoogle Scholar
  38. 38.
    Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nat Med. 2006;444:847–53.CrossRefGoogle Scholar
  39. 39.
    Ferranti SD, Mozaffarian D. The perfect storm: obesity, adipocyte dysfunction, and metabolic consequences. Clin Chem. 2008;54:945–55.CrossRefPubMedGoogle Scholar
  40. 40.
    Robin ED, Wong R. Mitochondrial DNA molecules and virtual number of mitochondria per cell in mammalian cells. J Cell Physiol. 1988;136:507–13.CrossRefPubMedGoogle Scholar
  41. 41.
    Cypess AM, Lehmann S, Kahn CR, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009;360:1509–17.CrossRefPubMedGoogle Scholar
  42. 42.
    Virtanen KA, Lidell ME, Nuutila P, et al. Functional brown adipose tissue in healthy adults. N Engl J Med. 2009;360:1518–25.CrossRefPubMedGoogle Scholar
  43. 43.
    Befroy DE, Petersen KF, Shulman GI, et al. Impaired mitochondrial substrate oxidation in muscle of insulin-resistant offspring of type 2 diabetic patients. Diabetes. 2007;56:1376–81.CrossRefPubMedGoogle Scholar
  44. 44.
    Hellmér J, Marcus C, Arner P, et al. Mechanisms for differences in lipolysis between human subcutaneous and omental fat cells. J Clin Endocrinol Metab. 1992;75(1):15–20.CrossRefPubMedGoogle Scholar
  45. 45.
    van Harmelen V, Dicker A, Arner P, et al. Increased lipolysis and decreased leptin production by human omental as compared with subcutaneous preadipocytes. Diabetes. 2002;51:2029–36.CrossRefPubMedGoogle Scholar
  46. 46.
    Fried SK, Bunkin DA, Greenberg AS. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J Clin Endocrinol Metab. 1998;83(3):847–50.CrossRefPubMedGoogle Scholar
  47. 47.
    Arvidsson E, Blomqvist L, Ryden M. Depot-specific differences in perilipin mRNA but not protein expression in obesity. J Intern Med. 2004;255:595–601.CrossRefPubMedGoogle Scholar
  48. 48.
    Kelley DE, Mandarino LJ. Fuel selection in human skeletal muscle in insulin resistance. Diabetes. 2000;49:677–83.CrossRefPubMedGoogle Scholar
  49. 49.
    Capkova M, Houstek J, Zeman J, et al. Activities of cytochrome c oxidase and citrate synthase in lymphocates of obese and normal-weight subjects. IJO. 2002;26:1110–7.CrossRefGoogle Scholar
  50. 50.
    Kim JY, Hickner RC, Houmard JA, et al. Lipid oxidation is reduced in obese human skeletal muscle. Am J Physiol Endocriol Metab. 2000;279:1039–44.Google Scholar
  51. 51.
    Crescenzo R, Bianco F, Iossa S, et al. Alterations in hepatic mitochondrial compartment in a model of obesity and insulin resistance. Obesity. 2008;16:958–64.CrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2009

Authors and Affiliations

  • Andrea Lindinger
    • 1
  • Ralph Peterli
    • 1
  • Thomas Peters
    • 2
  • Beatrice Kern
    • 1
  • Markus von Flüe
    • 1
  • Martine Calame
    • 3
  • Matthias Hoch
    • 3
  • Alex N. Eberle
    • 3
  • Peter W. Lindinger
    • 3
  1. 1.Surgical DepartmentSt. ClaraspitalBaselSwitzerland
  2. 2.Interdisciplinary Center of Nutritional and Metabolic DiseasesSt. ClaraspitalBaselSwitzerland
  3. 3.Laboratory of Endocrinology, Department of BiomedicineUniversity Hospital and University Children’s Hospital, BaselBaselSwitzerland

Personalised recommendations