Skip to main content
Top
Published in: Obesity Surgery 1/2010

01-01-2010 | Clinical Research

Mitochondrial DNA Content in Human Omental Adipose Tissue

Authors: Andrea Lindinger, Ralph Peterli, Thomas Peters, Beatrice Kern, Markus von Flüe, Martine Calame, Matthias Hoch, Alex N. Eberle, Peter W. Lindinger

Published in: Obesity Surgery | Issue 1/2010

Login to get access

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.
Literature
1.
go back to reference Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004;84:277–359.CrossRefPubMed Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004;84:277–359.CrossRefPubMed
2.
go back to reference Diamond F. The endocrine function of adipose tissue. Growth Genet Horm. 2002;18(2):17–22. Diamond F. The endocrine function of adipose tissue. Growth Genet Horm. 2002;18(2):17–22.
4.
go back to reference Maassen JA. Mitochondrial dysfunction in adipocytes: the culprit in type 2 diabetes? Diabetologia. 2006;49(4):619–20.CrossRefPubMed Maassen JA. Mitochondrial dysfunction in adipocytes: the culprit in type 2 diabetes? Diabetologia. 2006;49(4):619–20.CrossRefPubMed
5.
go back to reference Choo HJ, Kim JH, Kwon OB, et al. Mitochondria are impaired in the adipocytes of type 2 diabetic mice. Diabetologia. 2006;49:784–91.CrossRefPubMed Choo HJ, Kim JH, Kwon OB, et al. Mitochondria are impaired in the adipocytes of type 2 diabetic mice. Diabetologia. 2006;49:784–91.CrossRefPubMed
6.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
7.
go back to reference Petersen KF, Befroy D, Shulman GI, et al. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science. 2003;500(5622):1140–2.CrossRef Petersen KF, Befroy D, Shulman GI, et al. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science. 2003;500(5622):1140–2.CrossRef
8.
go back to reference Civitarese AE, Ravussin E. Minireview: mitochondrial energetics and insulin resistance. Endocrinology. 2007;149(3):950–4.CrossRef Civitarese AE, Ravussin E. Minireview: mitochondrial energetics and insulin resistance. Endocrinology. 2007;149(3):950–4.CrossRef
9.
10.
go back to reference Kuroshima A. Brown adipose tissue thermogenesis as a physiological strategy for adaptation. Jpn J Physiol. 1993;43(43):117.CrossRefPubMed Kuroshima A. Brown adipose tissue thermogenesis as a physiological strategy for adaptation. Jpn J Physiol. 1993;43(43):117.CrossRefPubMed
11.
go back to reference Justo R, Oliver J, Gianotti M. Brown adipose tissue mitochondrial subpopulations show different morphological and thermogenic characteristics. Mitochondrion. 2005;5(1):45–53.CrossRefPubMed Justo R, Oliver J, Gianotti M. Brown adipose tissue mitochondrial subpopulations show different morphological and thermogenic characteristics. Mitochondrion. 2005;5(1):45–53.CrossRefPubMed
12.
go back to reference Collins TJ, Bootman MD. Mitochondria are morphologically heterogenous within cells. J Exp Biol. 2003;206:1993–2000.CrossRefPubMed Collins TJ, Bootman MD. Mitochondria are morphologically heterogenous within cells. J Exp Biol. 2003;206:1993–2000.CrossRefPubMed
13.
go back to reference 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. 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.
14.
go back to reference 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.PubMed 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.PubMed
15.
go back to reference Kelly DP, Scarpulla RC. Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev. 2004;18:357–68.CrossRefPubMed Kelly DP, Scarpulla RC. Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev. 2004;18:357–68.CrossRefPubMed
16.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
17.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
18.
go back to reference Chan DC. Mitochondrial fusion and fission in mammals. Ann Rev Cell Dev Biol. 2006;22:79–99.CrossRef Chan DC. Mitochondrial fusion and fission in mammals. Ann Rev Cell Dev Biol. 2006;22:79–99.CrossRef
19.
go back to reference Detmer SA, Chan DC. Functions and dysfunctions of mitochondrial dynamics. Nat Rev Mol Cell Biol. 2007;8:870–9.CrossRefPubMed Detmer SA, Chan DC. Functions and dysfunctions of mitochondrial dynamics. Nat Rev Mol Cell Biol. 2007;8:870–9.CrossRefPubMed
20.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
21.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
22.
go back to reference 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.PubMed 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.PubMed
23.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
24.
go back to reference 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.CrossRef 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.CrossRef
25.
go back to reference Bogacka I, Xie H, Smith SR, et al. Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo. Diabetes. 2005;54:1392–9.CrossRefPubMed Bogacka I, Xie H, Smith SR, et al. Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo. Diabetes. 2005;54:1392–9.CrossRefPubMed
26.
go back to reference Pinheiro JC, Bates DM. Mixed-effects models in S and S-PLUS. Springer: New York; 2000. Pinheiro JC, Bates DM. Mixed-effects models in S and S-PLUS. Springer: New York; 2000.
27.
go back to reference 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.CrossRef 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.CrossRef
28.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
29.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
30.
go back to reference Needergard J, Bengtssen T. Unexpected evidence of brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab. 2007;293:E444–52.CrossRef Needergard J, Bengtssen T. Unexpected evidence of brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab. 2007;293:E444–52.CrossRef
31.
go back to reference Wajchenberg BL. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev. 2000;21(6):697–738.CrossRefPubMed Wajchenberg BL. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev. 2000;21(6):697–738.CrossRefPubMed
32.
go back to reference Maassen JA. Mitochondrial diabetes: pathophysiology, clinical presentation, and genetic analysis. Am J Med Gen (Semin. Med. Genet.). 2002;115:66–70.CrossRef Maassen JA. Mitochondrial diabetes: pathophysiology, clinical presentation, and genetic analysis. Am J Med Gen (Semin. Med. Genet.). 2002;115:66–70.CrossRef
33.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
34.
35.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
36.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
37.
go back to reference Rajala MW, Scherer PE. Minireview: the adipocyte—at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology. 2003;144(9):3765–73.CrossRefPubMed Rajala MW, Scherer PE. Minireview: the adipocyte—at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology. 2003;144(9):3765–73.CrossRefPubMed
38.
go back to reference Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nat Med. 2006;444:847–53.CrossRef Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nat Med. 2006;444:847–53.CrossRef
39.
go back to reference Ferranti SD, Mozaffarian D. The perfect storm: obesity, adipocyte dysfunction, and metabolic consequences. Clin Chem. 2008;54:945–55.CrossRefPubMed Ferranti SD, Mozaffarian D. The perfect storm: obesity, adipocyte dysfunction, and metabolic consequences. Clin Chem. 2008;54:945–55.CrossRefPubMed
40.
go back to reference Robin ED, Wong R. Mitochondrial DNA molecules and virtual number of mitochondria per cell in mammalian cells. J Cell Physiol. 1988;136:507–13.CrossRefPubMed Robin ED, Wong R. Mitochondrial DNA molecules and virtual number of mitochondria per cell in mammalian cells. J Cell Physiol. 1988;136:507–13.CrossRefPubMed
41.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
42.
go back to reference Virtanen KA, Lidell ME, Nuutila P, et al. Functional brown adipose tissue in healthy adults. N Engl J Med. 2009;360:1518–25.CrossRefPubMed Virtanen KA, Lidell ME, Nuutila P, et al. Functional brown adipose tissue in healthy adults. N Engl J Med. 2009;360:1518–25.CrossRefPubMed
43.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
44.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
45.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
46.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
47.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
48.
go back to reference Kelley DE, Mandarino LJ. Fuel selection in human skeletal muscle in insulin resistance. Diabetes. 2000;49:677–83.CrossRefPubMed Kelley DE, Mandarino LJ. Fuel selection in human skeletal muscle in insulin resistance. Diabetes. 2000;49:677–83.CrossRefPubMed
49.
go back to reference 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.CrossRef 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.CrossRef
50.
go back to reference 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. 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.
51.
go back to reference 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.CrossRef 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.CrossRef
Metadata
Title
Mitochondrial DNA Content in Human Omental Adipose Tissue
Authors
Andrea Lindinger
Ralph Peterli
Thomas Peters
Beatrice Kern
Markus von Flüe
Martine Calame
Matthias Hoch
Alex N. Eberle
Peter W. Lindinger
Publication date
01-01-2010
Publisher
Springer-Verlag
Published in
Obesity Surgery / Issue 1/2010
Print ISSN: 0960-8923
Electronic ISSN: 1708-0428
DOI
https://doi.org/10.1007/s11695-009-9987-3

Other articles of this Issue 1/2010

Obesity Surgery 1/2010 Go to the issue