Skip to main content
Erschienen in: Diabetologia 12/2007

01.12.2007 | Article

Strong association between mitochondrial DNA copy number and lipogenesis in human white adipose tissue

verfasst von: M. Kaaman, L. M. Sparks, V. van Harmelen, S. R. Smith, E. Sjölin, I. Dahlman, P. Arner

Erschienen in: Diabetologia | Ausgabe 12/2007

Einloggen, um Zugang zu erhalten

Abstract

Aims/hypothesis

Recent studies suggest a link between insulin resistance and mitochondrial function in white fat cells. The aim of this study was to evaluate adipocyte mitochondrial DNA (mtDNA) copy number in relation to adipocyte and clinical variables that are related to insulin sensitivity.

Methods

We studied a group of 148 healthy volunteers with a large inter-individual variation in BMI. Relative amounts of mtDNA and nuclear DNA were determined by quantitative RT-PCR. The mtDNA:nuclear DNA ratio reflects the tissue concentration of mtDNA per cell.

Results

The mtDNA copy number was enriched in adipocytes of adipose tissue and decreased slightly by ageing (p = 0.015) and increasing BMI (p = 0.004); however, it was not influenced by sex, energy-restricted diets or marked long-term weight reduction. Adipose mtDNA copy number was not independently related to resting energy expenditure, overall insulin sensitivity or adipocyte lipolysis. However, it showed a strong positive correlation with basal (p = 0.0012) and insulin-stimulated lipogenesis (p < 0.0001) in fat cells, independently of age and BMI, and a weak positive correlation with levels of mRNA from several genes involved in mitochondrial oxidative capacity (r = 0.2–0.3).

Conclusions/interpretation

The mtDNA copy number in human white fat cells is fairly stable within healthy individuals. It is not influenced by sex or weight loss and is not important for overall insulin sensitivity or energy expenditure at rest. However, it is strongly related to adipocyte lipogenesis and weakly to mitochondrial oxidative capacity, suggesting that adipocyte mitochondria are, above all, local regulators.
Literatur
1.
Zurück zum Zitat Wu Z, Puigserver P, Andersson U et al (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98:115–124CrossRefPubMed Wu Z, Puigserver P, Andersson U et al (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98:115–124CrossRefPubMed
2.
Zurück zum Zitat Tiraby C, Tavernier G, Lefort C et al (2003) Acquirement of brown fat cell features by human white adipocytes. J Biol Chem 278:33370–33376CrossRefPubMed Tiraby C, Tavernier G, Lefort C et al (2003) Acquirement of brown fat cell features by human white adipocytes. J Biol Chem 278:33370–33376CrossRefPubMed
3.
Zurück zum Zitat Mootha VK, Lindgren CM, Eriksson KF et al (2003) PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 34:267–273CrossRefPubMed Mootha VK, Lindgren CM, Eriksson KF et al (2003) PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 34:267–273CrossRefPubMed
4.
Zurück zum Zitat Patti ME, Butte AJ, Crunkhorn S et al (2003) Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1. Proc Natl Acad Sci USA 100:8466–8471CrossRefPubMed Patti ME, Butte AJ, Crunkhorn S et al (2003) Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1. Proc Natl Acad Sci USA 100:8466–8471CrossRefPubMed
5.
Zurück zum Zitat Petersen KF, Befroy D, Dufour S et al (2003) Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 300:1140–1142CrossRefPubMed Petersen KF, Befroy D, Dufour S et al (2003) Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 300:1140–1142CrossRefPubMed
6.
Zurück zum Zitat Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI (2004) Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 350:664–671CrossRefPubMed Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI (2004) Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 350:664–671CrossRefPubMed
7.
Zurück zum Zitat Wilson-Fritch L, Nicoloro S, Chouinard M et al (2004) Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone. J Clin Invest 114:1281–1289CrossRefPubMed Wilson-Fritch L, Nicoloro S, Chouinard M et al (2004) Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone. J Clin Invest 114:1281–1289CrossRefPubMed
8.
Zurück zum Zitat Wang T, Zang Y, Ling W, Corkey BE, Guo W (2003) Metabolic partitioning of endogenous fatty acid in adipocytes. Obes Res 11:880–887PubMedCrossRef Wang T, Zang Y, Ling W, Corkey BE, Guo W (2003) Metabolic partitioning of endogenous fatty acid in adipocytes. Obes Res 11:880–887PubMedCrossRef
9.
Zurück zum Zitat Sorbris R, Monti M, Nilsson-Ehle P, Wadso I (1982) Heat production by adipocytes from obese subjects before and after weight reduction. Metabolism 31:973–978CrossRefPubMed Sorbris R, Monti M, Nilsson-Ehle P, Wadso I (1982) Heat production by adipocytes from obese subjects before and after weight reduction. Metabolism 31:973–978CrossRefPubMed
10.
Zurück zum Zitat Bogacka I, Ukropcova B, McNeil M, Gimble JM, Smith SR (2005) Structural and functional consequences of mitochondrial biogenesis in human adipocytes in vitro. J Clin Endocrinol Metab 90:6650–6656CrossRefPubMed Bogacka I, Ukropcova B, McNeil M, Gimble JM, Smith SR (2005) Structural and functional consequences of mitochondrial biogenesis in human adipocytes in vitro. J Clin Endocrinol Metab 90:6650–6656CrossRefPubMed
11.
Zurück zum Zitat Dahlman I, Forsgren M, Sjogren A (2006) Downregulation of electron transport chain genes in visceral adipose tissue in type 2 diabetes independent of obesity and possibly involving tumor necrosis factor-alpha. Diabetes 55:1792–1799CrossRefPubMed Dahlman I, Forsgren M, Sjogren A (2006) Downregulation of electron transport chain genes in visceral adipose tissue in type 2 diabetes independent of obesity and possibly involving tumor necrosis factor-alpha. Diabetes 55:1792–1799CrossRefPubMed
12.
Zurück zum Zitat Bogacka I, Xie H, Bray GA, Smith SR (2005) Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo. Diabetes 54:1392–1399CrossRefPubMed Bogacka I, Xie H, Bray GA, Smith SR (2005) Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo. Diabetes 54:1392–1399CrossRefPubMed
13.
Zurück zum Zitat Boden G, Homko C, Mozzoli M, Showe LC, Nichols C, Cheung P (2005) Thiazolidinediones upregulate fatty acid uptake and oxidation in adipose tissue of diabetic patients. Diabetes 54:880–885CrossRefPubMed Boden G, Homko C, Mozzoli M, Showe LC, Nichols C, Cheung P (2005) Thiazolidinediones upregulate fatty acid uptake and oxidation in adipose tissue of diabetic patients. Diabetes 54:880–885CrossRefPubMed
14.
Zurück zum Zitat Flachs P, Horakova O, Brauner P et al (2005) Polyunsaturated fatty acids of marine origin upregulate mitochondrial biogenesis and induce beta-oxidation in white fat. Diabetologia 48:2365–2375CrossRefPubMed Flachs P, Horakova O, Brauner P et al (2005) Polyunsaturated fatty acids of marine origin upregulate mitochondrial biogenesis and induce beta-oxidation in white fat. Diabetologia 48:2365–2375CrossRefPubMed
15.
Zurück zum Zitat Kopecky J, Rossmeisl M, Flachs P, Bardova K, Brauner P (2001) Mitochondrial uncoupling and lipid metabolism in adipocytes. Biochem Soc Trans 29:791–797CrossRefPubMed Kopecky J, Rossmeisl M, Flachs P, Bardova K, Brauner P (2001) Mitochondrial uncoupling and lipid metabolism in adipocytes. Biochem Soc Trans 29:791–797CrossRefPubMed
16.
Zurück zum Zitat Arvidsson E, Viguerie N, Andersson I, Verdich C, Langin D, Arner P (2004) Effects of different hypocaloric diets on protein secretion from adipose tissue of obese women. Diabetes 53:1966–1971CrossRefPubMed Arvidsson E, Viguerie N, Andersson I, Verdich C, Langin D, Arner P (2004) Effects of different hypocaloric diets on protein secretion from adipose tissue of obese women. Diabetes 53:1966–1971CrossRefPubMed
17.
Zurück zum Zitat Lofgren P, Hoffstedt J, Naslund E, Wiren M, Arner P (2005) Prospective and controlled studies of the actions of insulin and catecholamine in fat cells of obese women following weight reduction. Diabetologia 48:2334–2342CrossRefPubMed Lofgren P, Hoffstedt J, Naslund E, Wiren M, Arner P (2005) Prospective and controlled studies of the actions of insulin and catecholamine in fat cells of obese women following weight reduction. Diabetologia 48:2334–2342CrossRefPubMed
18.
Zurück zum Zitat Levy JC, Matthews DR, Hermans MP (1998) Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care 21:2191–2192CrossRefPubMed Levy JC, Matthews DR, Hermans MP (1998) Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care 21:2191–2192CrossRefPubMed
19.
Zurück zum Zitat Bolinder J, Lithell H, Skarfors E, Arner P (1986) Effects of obesity, hyperinsulinemia, and glucose intolerance on insulin action in adipose tissue of sixty-year-old men. Diabetes 35:282–290CrossRefPubMed Bolinder J, Lithell H, Skarfors E, Arner P (1986) Effects of obesity, hyperinsulinemia, and glucose intolerance on insulin action in adipose tissue of sixty-year-old men. Diabetes 35:282–290CrossRefPubMed
20.
Zurück zum Zitat Rodbell M (1964) Metabolism of isolated fat cells. I. Effects of hormones on glucose metabolism and lipolysis. J Biol Chem 239:375–380PubMed Rodbell M (1964) Metabolism of isolated fat cells. I. Effects of hormones on glucose metabolism and lipolysis. J Biol Chem 239:375–380PubMed
21.
Zurück zum Zitat van Harmelen V, Dicker A, Ryden M et al (2002) Increased lipolysis and decreased leptin production by human omental as compared with subcutaneous preadipocytes. Diabetes 51:2029–2036CrossRefPubMed van Harmelen V, Dicker A, Ryden M et al (2002) Increased lipolysis and decreased leptin production by human omental as compared with subcutaneous preadipocytes. Diabetes 51:2029–2036CrossRefPubMed
22.
Zurück zum Zitat He L, Chinnery PF, Durham SE et al (2002) Detection and quantification of mitochondrial DNA deletions in individual cells by real-time PCR. Nucleic Acids Res 30:e68CrossRefPubMed He L, Chinnery PF, Durham SE et al (2002) Detection and quantification of mitochondrial DNA deletions in individual cells by real-time PCR. Nucleic Acids Res 30:e68CrossRefPubMed
23.
Zurück zum Zitat Thorne A, Lonnqvist F, Apelman J, Hellers G, Arner P (2002) A pilot study of long-term effects of a novel obesity treatment: omentectomy in connection with adjustable gastric banding. Int J Obes Relat Metab Disord 26:193–199CrossRefPubMed Thorne A, Lonnqvist F, Apelman J, Hellers G, Arner P (2002) A pilot study of long-term effects of a novel obesity treatment: omentectomy in connection with adjustable gastric banding. Int J Obes Relat Metab Disord 26:193–199CrossRefPubMed
24.
Zurück zum Zitat Gahan ME, Miller F, Lewin SR et al (2001) Quantification of mitochondrial DNA in peripheral blood mononuclear cells and subcutaneous fat using real-time polymerase chain reaction. J Clin Virol 22:241–247CrossRefPubMed Gahan ME, Miller F, Lewin SR et al (2001) Quantification of mitochondrial DNA in peripheral blood mononuclear cells and subcutaneous fat using real-time polymerase chain reaction. J Clin Virol 22:241–247CrossRefPubMed
25.
Zurück zum Zitat Rodrigue-Way A, Demers A, Ong H, Tremblay A (2007) A growth hormone-releasing peptide promotes mitochondrial biogenesis and a fat burning-like phenotype through scavenger receptor CD36 in white adipocytes. Endocrinology 148:1009–1018CrossRefPubMed Rodrigue-Way A, Demers A, Ong H, Tremblay A (2007) A growth hormone-releasing peptide promotes mitochondrial biogenesis and a fat burning-like phenotype through scavenger receptor CD36 in white adipocytes. Endocrinology 148:1009–1018CrossRefPubMed
Metadaten
Titel
Strong association between mitochondrial DNA copy number and lipogenesis in human white adipose tissue
verfasst von
M. Kaaman
L. M. Sparks
V. van Harmelen
S. R. Smith
E. Sjölin
I. Dahlman
P. Arner
Publikationsdatum
01.12.2007
Verlag
Springer-Verlag
Erschienen in
Diabetologia / Ausgabe 12/2007
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-007-0818-6

Weitere Artikel der Ausgabe 12/2007

Diabetologia 12/2007 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Echinokokkose medikamentös behandeln oder operieren?

06.05.2024 DCK 2024 Kongressbericht

Die Therapie von Echinokokkosen sollte immer in spezialisierten Zentren erfolgen. Eine symptomlose Echinokokkose kann – egal ob von Hunde- oder Fuchsbandwurm ausgelöst – konservativ erfolgen. Wenn eine Op. nötig ist, kann es sinnvoll sein, vorher Zysten zu leeren und zu desinfizieren. 

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Proximale Humerusfraktur: Auch 100-Jährige operieren?

01.05.2024 DCK 2024 Kongressbericht

Mit dem demographischen Wandel versorgt auch die Chirurgie immer mehr betagte Menschen. Von Entwicklungen wie Fast-Track können auch ältere Menschen profitieren und bei proximaler Humerusfraktur können selbst manche 100-Jährige noch sicher operiert werden.

Die „Zehn Gebote“ des Endokarditis-Managements

30.04.2024 Endokarditis Leitlinie kompakt

Worauf kommt es beim Management von Personen mit infektiöser Endokarditis an? Eine Kardiologin und ein Kardiologe fassen die zehn wichtigsten Punkte der neuen ESC-Leitlinie zusammen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.