Skip to main content
Erschienen in: Diabetologia 3/2004

01.03.2004 | Article

Effect of testosterone on lipolysis in human pre-adipocytes from different fat depots

verfasst von: A. Dicker, M. Rydén, E. Näslund, I. E. Muehlen, M. Wirén, M. Lafontan, Prof. P. Arner

Erschienen in: Diabetologia | Ausgabe 3/2004

Einloggen, um Zugang zu erhalten

Abstract

Aim/hypothesis

Regional differences in lipolysis, with higher lipolytic activity in visceral than subcutaneous fat, are important for the development of insulin resistance and might be influenced by testosterone.

Methods

We studied testosterone-regulated lipolysis and protein expression (by western blot) in fully differentiated pre-adipocytes from visceral (omental) and abdominal subcutaneous adipose tissue from 52 human subjects. These cells were isolated and cultured in a serum-free medium.

Results

Testosterone caused a specific, time- and concentration-dependent 50% reduction of catecholamine-stimulated lipolysis in the subcutaneous depot. Half of the maximum effect occurred at 10 nmol/l. The inhibitory effect was due to the inability of β-adrenoceptors and cyclic AMP to stimulate the protein kinase A, hormone-sensitive lipase complex. Testosterone caused a depot-specific 50% reduction of the protein expression of hormone-sensitive lipase and β2-adrenoceptors in differentiated subcutaneous pre-adipocytes, but no change in β1-adrenoceptors, protein kinase A subunits or perilipin expression. In contrast, testosterone had no effect on lipolysis or protein expression in the visceral depot. However, testosterone receptors were present in both depots, and the hormone inhibited adipocyte leptin secretion. Similar effects on lipolysis were observed with dihydrotestosterone.

Conclusions/interpretation

Testosterone in physiological concentrations causes a depot-specific reduction of catecholamine-stimulated lipolysis in subcutaneous fat cells, probably due to reduced protein expression of β2-adrenoceptors and hormone-sensitive lipase. This could be an important pathogenic factor underlying regional differences in lipolysis and development of insulin resistance and hyperandrogenic polycystic ovary syndrome.
Literatur
1.
Zurück zum Zitat Bergman RN, Citters GW van, Mittelman SD et al. (2001) Central role of the adipocyte in the metabolic syndrome. J Investig Med 49:119–126CrossRefPubMed Bergman RN, Citters GW van, Mittelman SD et al. (2001) Central role of the adipocyte in the metabolic syndrome. J Investig Med 49:119–126CrossRefPubMed
2.
Zurück zum Zitat Zacur HA (2001) Polycystic ovary syndrome, hyperandrogenism and insulin resistance. Obstet Gynecol Clin North Am 28:21–33CrossRefPubMed Zacur HA (2001) Polycystic ovary syndrome, hyperandrogenism and insulin resistance. Obstet Gynecol Clin North Am 28:21–33CrossRefPubMed
3.
Zurück zum Zitat Chaldakov GN, Stankulov IS, Hristova M, Ghenev PI (2003) Adipobiology of disease: adipokines and adipokine-targeted pharmacology. Curr Pharm Des 9:1023–1031CrossRefPubMed Chaldakov GN, Stankulov IS, Hristova M, Ghenev PI (2003) Adipobiology of disease: adipokines and adipokine-targeted pharmacology. Curr Pharm Des 9:1023–1031CrossRefPubMed
4.
Zurück zum Zitat Cederberg A, Enerback S (2003) Insulin resistance and type 2 diabetes—an adipocentric view. Curr Mol Med 3:107–125CrossRefPubMed Cederberg A, Enerback S (2003) Insulin resistance and type 2 diabetes—an adipocentric view. Curr Mol Med 3:107–125CrossRefPubMed
5.
Zurück zum Zitat Arner P (2003) The adipocyte in insulin resistance: key molecules and the impact of the thiazolidinediones. Trends Endocrinol Metab14:137–145CrossRef Arner P (2003) The adipocyte in insulin resistance: key molecules and the impact of the thiazolidinediones. Trends Endocrinol Metab14:137–145CrossRef
7.
Zurück zum Zitat Montague CT, O’Rahilly S (2000) The perils of portliness: causes and consequences of visceral adipocytes. Diabetes 49:883–888CrossRefPubMed Montague CT, O’Rahilly S (2000) The perils of portliness: causes and consequences of visceral adipocytes. Diabetes 49:883–888CrossRefPubMed
8.
Zurück zum Zitat Wajchenberg BL (2000) Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrom. Endocr Rev 21:697–738CrossRefPubMed Wajchenberg BL (2000) Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrom. Endocr Rev 21:697–738CrossRefPubMed
9.
Zurück zum Zitat Gasteyger C, Tremblay A (2002) Metabolic impact of body fat distribution. J Endocrinol Invest 25:876–883CrossRefPubMed Gasteyger C, Tremblay A (2002) Metabolic impact of body fat distribution. J Endocrinol Invest 25:876–883CrossRefPubMed
10.
11.
Zurück zum Zitat Lonnqvist F, Thorne A, Large V, Arner P (1997) Sex differences in visceral fat lipolysis and metabolic complications of obesity. Arterioscler Thromb Vasc Biol 17:1472–1480CrossRefPubMed Lonnqvist F, Thorne A, Large V, Arner P (1997) Sex differences in visceral fat lipolysis and metabolic complications of obesity. Arterioscler Thromb Vasc Biol 17:1472–1480CrossRefPubMed
12.
Zurück zum Zitat Lofgren P, Hoffstedt J, Ryden M et al. (2002) Major gender differences in the lipolytic capacity of abdominal subcutaneous fat cells in obesity observed before and after long-term weight reduction. J Clin Endocrinol Metab 87:764–771CrossRefPubMed Lofgren P, Hoffstedt J, Ryden M et al. (2002) Major gender differences in the lipolytic capacity of abdominal subcutaneous fat cells in obesity observed before and after long-term weight reduction. J Clin Endocrinol Metab 87:764–771CrossRefPubMed
13.
Zurück zum Zitat Ek I, Arner P, Bergqvist A, Carlstrom K, Wahrenberg H (1997) Impaired adipocyte lipolysis in nonobese women with the polycystic ovary syndrome: a possible link to insulin resistance? J Clin Endocrinol Metab 82:1147–1153PubMed Ek I, Arner P, Bergqvist A, Carlstrom K, Wahrenberg H (1997) Impaired adipocyte lipolysis in nonobese women with the polycystic ovary syndrome: a possible link to insulin resistance? J Clin Endocrinol Metab 82:1147–1153PubMed
14.
Zurück zum Zitat Ek I, Arner P, Ryden M et al. (2002) A unique defect in the regulation of visceral fat cell lipolysis in the polycystic ovary syndrome as an early link to insulin resistance. Diabetes 51:484–492CrossRefPubMed Ek I, Arner P, Ryden M et al. (2002) A unique defect in the regulation of visceral fat cell lipolysis in the polycystic ovary syndrome as an early link to insulin resistance. Diabetes 51:484–492CrossRefPubMed
15.
Zurück zum Zitat Harmelen V van, 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 Harmelen V van, 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
16.
Zurück zum Zitat Hauner H, Entenmann G, Wabitsch M et al. (1989) Promoting effect of glucocorticoids on the differentiation of human adipocyte precursor cells cultured in a chemically defined medium. J Clin Invest 84:1663–1670CrossRefPubMedPubMedCentral Hauner H, Entenmann G, Wabitsch M et al. (1989) Promoting effect of glucocorticoids on the differentiation of human adipocyte precursor cells cultured in a chemically defined medium. J Clin Invest 84:1663–1670CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Hellmer J, Arner P, Lundin A (1989) Automatic luminometric kinetic assay of glycerol for lipolysis studies. Anal Biochem 177:132–137CrossRefPubMed Hellmer J, Arner P, Lundin A (1989) Automatic luminometric kinetic assay of glycerol for lipolysis studies. Anal Biochem 177:132–137CrossRefPubMed
18.
Zurück zum Zitat Large V, Arner P, Reynisdottir S et al. (1998) Hormone-sensitive lipase expression and activity in relation to lipolysis in human fat cells. J Lipid Res 39:1688–1695PubMed Large V, Arner P, Reynisdottir S et al. (1998) Hormone-sensitive lipase expression and activity in relation to lipolysis in human fat cells. J Lipid Res 39:1688–1695PubMed
19.
Zurück zum Zitat Lafontan M, Barbe P, Galitzky J et al. (1997) Adrenergic regulation of adipocyte metabolism. Hum Reprod 1:6–20CrossRef Lafontan M, Barbe P, Galitzky J et al. (1997) Adrenergic regulation of adipocyte metabolism. Hum Reprod 1:6–20CrossRef
20.
Zurück zum Zitat Blaak E (2001) Gender differences in fat metabolism. Curr Opin Clin Nutr Metab Care 4:499–502CrossRefPubMed Blaak E (2001) Gender differences in fat metabolism. Curr Opin Clin Nutr Metab Care 4:499–502CrossRefPubMed
21.
Zurück zum Zitat Xu XF, De Pergola G, Bjorntorp P(1990) The effects of androgens on the regulation of lipolysis in adipose precursor cells. Endocrinology 126:1229–1234CrossRefPubMed Xu XF, De Pergola G, Bjorntorp P(1990) The effects of androgens on the regulation of lipolysis in adipose precursor cells. Endocrinology 126:1229–1234CrossRefPubMed
22.
Zurück zum Zitat De Pergola G, Holmang A, Svedberg J, Giorgino R, Bjorntorp P (1990) Testosterone treatment of ovariectomized rats: effects on lipolysis regulation in adipocytes. Acta Endocrinol 123:61–66 De Pergola G, Holmang A, Svedberg J, Giorgino R, Bjorntorp P (1990) Testosterone treatment of ovariectomized rats: effects on lipolysis regulation in adipocytes. Acta Endocrinol 123:61–66
23.
Zurück zum Zitat Xu XF, De Pergola G, Bjorntorp P (1991) Testosterone increases lipolysis and the number of beta-adrenoceptors in male rat adipocytes. Endocrinology 128:379–382CrossRefPubMed Xu XF, De Pergola G, Bjorntorp P (1991) Testosterone increases lipolysis and the number of beta-adrenoceptors in male rat adipocytes. Endocrinology 128:379–382CrossRefPubMed
24.
Zurück zum Zitat Rebuffe-Scrive M, Marin P, Bjorntorp P (1991) Effect of testosterone on abdominal adipose tissue in men. Int J Obes 15:791–795PubMed Rebuffe-Scrive M, Marin P, Bjorntorp P (1991) Effect of testosterone on abdominal adipose tissue in men. Int J Obes 15:791–795PubMed
25.
Zurück zum Zitat Marin P, Holmang S, Jonsson L et al. (1992) The effects of testosterone treatment on body composition and metabolism in middle-aged obese men. Int J Obes Relat Metab Disord 16:991–997PubMed Marin P, Holmang S, Jonsson L et al. (1992) The effects of testosterone treatment on body composition and metabolism in middle-aged obese men. Int J Obes Relat Metab Disord 16:991–997PubMed
26.
Zurück zum Zitat Marin P, Lonn L, Andersson B et al. (1996) Assimilation of triglycerides in subcutaneous and intraabdominal adipose tissue in vivo in men: effects of testosterone. J Clin Endocrinol Metab 81:1018–1022PubMed Marin P, Lonn L, Andersson B et al. (1996) Assimilation of triglycerides in subcutaneous and intraabdominal adipose tissue in vivo in men: effects of testosterone. J Clin Endocrinol Metab 81:1018–1022PubMed
27.
Zurück zum Zitat Dieudonne MN, Pecquery R, Boumediene A, Leneveu MC, Giudicelli Y (1998) Androgen receptors in human preadipocytes and adipocytes: regional specificities and regulation by sex steroids. Am J Physiol 274:C1645–C1652PubMed Dieudonne MN, Pecquery R, Boumediene A, Leneveu MC, Giudicelli Y (1998) Androgen receptors in human preadipocytes and adipocytes: regional specificities and regulation by sex steroids. Am J Physiol 274:C1645–C1652PubMed
28.
Zurück zum Zitat Joyner J, Hutley L, Cameron D (2002) Intrinsic regional differences in androgen receptors and dihydrotestosterone metabolism in human preadipocytes. Horm Metab Res 34:223–228CrossRefPubMed Joyner J, Hutley L, Cameron D (2002) Intrinsic regional differences in androgen receptors and dihydrotestosterone metabolism in human preadipocytes. Horm Metab Res 34:223–228CrossRefPubMed
29.
Zurück zum Zitat Ryden M, Dicker A, Gotherstrom C et al. (2003) Functional characterization of human mesenchymal stem cell-derived adipocytes. Biochem Biophys Res Commun 311:391–397CrossRefPubMed Ryden M, Dicker A, Gotherstrom C et al. (2003) Functional characterization of human mesenchymal stem cell-derived adipocytes. Biochem Biophys Res Commun 311:391–397CrossRefPubMed
30.
Zurück zum Zitat Wabitsch M, Blum WF, Muche R et al. (1997) Contribution of androgens to the gender difference in leptin production in obese children and adolescents. J Clin Invest 100:808–813CrossRefPubMedPubMedCentral Wabitsch M, Blum WF, Muche R et al. (1997) Contribution of androgens to the gender difference in leptin production in obese children and adolescents. J Clin Invest 100:808–813CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Anderson LA, McTernan PG, Barnett AH, Kumar S (2001) The effects of androgens and estrogens on preadipocyte proliferation in human adipose tissue: influence of gender and site. J Clin Endocrinol Metab 86:5045–5051CrossRefPubMed Anderson LA, McTernan PG, Barnett AH, Kumar S (2001) The effects of androgens and estrogens on preadipocyte proliferation in human adipose tissue: influence of gender and site. J Clin Endocrinol Metab 86:5045–5051CrossRefPubMed
32.
Zurück zum Zitat Londos C, Brasaemle DL, Schultz CJ, Segrest JP, Kimmel AR (1999) Perilipins, ADRP, and other proteins that associate with intracellular neutral lipid droplets in animal cells. Semin Cell Dev Biol 10:51–58CrossRefPubMed Londos C, Brasaemle DL, Schultz CJ, Segrest JP, Kimmel AR (1999) Perilipins, ADRP, and other proteins that associate with intracellular neutral lipid droplets in animal cells. Semin Cell Dev Biol 10:51–58CrossRefPubMed
33.
Zurück zum Zitat McKnight GS, Cummings DE, Amieux PS et al. (1998) Cyclic AMP, PKA, and the physiological regulation of adiposity. Recent Prog Horm Res 53:139–159PubMed McKnight GS, Cummings DE, Amieux PS et al. (1998) Cyclic AMP, PKA, and the physiological regulation of adiposity. Recent Prog Horm Res 53:139–159PubMed
34.
Zurück zum Zitat Holm C, Osterlund T, Laurell H, Contreras JA (2000) Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Annu Rev Nutr 20:365–393CrossRefPubMed Holm C, Osterlund T, Laurell H, Contreras JA (2000) Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Annu Rev Nutr 20:365–393CrossRefPubMed
35.
Zurück zum Zitat Anderson LA, McTernan PG, Harte AL, Barnett AH, Kumar S (2002)The regulation of HSL and LPL expression by DHT and flutamide in human subcutaneous adipose tissue. Diabetes Obes Metab 4:209–213CrossRefPubMed Anderson LA, McTernan PG, Harte AL, Barnett AH, Kumar S (2002)The regulation of HSL and LPL expression by DHT and flutamide in human subcutaneous adipose tissue. Diabetes Obes Metab 4:209–213CrossRefPubMed
36.
Zurück zum Zitat Lacasa D, Le Liepvre X, Ferre P, Dugail I (2001) Progesterone stimulates adipocyte determination and differentiation 1/sterol regulatory element-binding protein 1c gene expression. Potential mechanism for the lipogenic effect of progesterone in adipose tissue. J Biol Chem 276:11512–11516CrossRefPubMed Lacasa D, Le Liepvre X, Ferre P, Dugail I (2001) Progesterone stimulates adipocyte determination and differentiation 1/sterol regulatory element-binding protein 1c gene expression. Potential mechanism for the lipogenic effect of progesterone in adipose tissue. J Biol Chem 276:11512–11516CrossRefPubMed
37.
Zurück zum Zitat Rodriguez AM, Monjo M, Roca P, Palou A (2002) Opposite actions of testosterone and progesterone on UCP1 mRNA expression in cultured brown adipocytes. Cell Mol Life Sci 59:1714–1723CrossRefPubMed Rodriguez AM, Monjo M, Roca P, Palou A (2002) Opposite actions of testosterone and progesterone on UCP1 mRNA expression in cultured brown adipocytes. Cell Mol Life Sci 59:1714–1723CrossRefPubMed
Metadaten
Titel
Effect of testosterone on lipolysis in human pre-adipocytes from different fat depots
verfasst von
A. Dicker
M. Rydén
E. Näslund
I. E. Muehlen
M. Wirén
M. Lafontan
Prof. P. Arner
Publikationsdatum
01.03.2004
Verlag
Springer Berlin Heidelberg
Erschienen in
Diabetologia / Ausgabe 3/2004
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-003-1324-0

Weitere Artikel der Ausgabe 3/2004

Diabetologia 3/2004 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Alphablocker schützt vor Miktionsproblemen nach der Biopsie

16.05.2024 alpha-1-Rezeptorantagonisten Nachrichten

Nach einer Prostatabiopsie treten häufig Probleme beim Wasserlassen auf. Ob sich das durch den periinterventionellen Einsatz von Alphablockern verhindern lässt, haben australische Mediziner im Zuge einer Metaanalyse untersucht.

Eingreifen von Umstehenden rettet vor Erstickungstod!

15.05.2024 Fremdkörperaspiration Nachrichten

Wer sich an einem Essensrest verschluckt und um Luft ringt, benötigt vor allem rasche Hilfe. Dass Umstehende nur in jedem zweiten Erstickungsnotfall bereit waren, diese zu leisten, ist das ernüchternde Ergebnis einer Beobachtungsstudie aus Japan. Doch es gibt auch eine gute Nachricht.

Neue S3-Leitlinie zur unkomplizierten Zystitis: Auf Antibiotika verzichten?

15.05.2024 Harnwegsinfektionen Nachrichten

Welche Antibiotika darf man bei unkomplizierter Zystitis verwenden und wovon sollte man die Finger lassen? Welche pflanzlichen Präparate können helfen? Was taugt der zugelassene Impfstoff? Antworten vom Koordinator der frisch überarbeiteten S3-Leitlinie, Prof. Florian Wagenlehner.

Schadet Ärger den Gefäßen?

14.05.2024 Arteriosklerose Nachrichten

In einer Studie aus New York wirkte sich Ärger kurzfristig deutlich negativ auf die Endothelfunktion gesunder Probanden aus. Möglicherweise hat dies Einfluss auf die kardiovaskuläre Gesundheit.

Update Innere Medizin

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