Abstract
BACKGROUND: Leptin is an adipose protein regulating food intake in the hypothalamus. Animal studies have suggested that leptin also acts in an auto-/paracrine fashion on adipose cell function.
OBJECTIVE: The aim of this study was to investigate the effects of leptin on the differentiation and metabolism of cultured human adipocytes.
MATERIAL: Adipose tissue from young healthy, lean women (body mass index (BMI) <27 kg/m2) undergoing elective mammary reduction surgery and young obese individuals (BMI>40 kg/m2) undergoing laparoscopic gastric banding.
METHODS: Human preadipocytes in primary culture were induced to undergo differentiation by defined adipogenic factors. Mature adipocytes were isolated by collagenase digestion and kept in culture suspension. Glycero-3-phosphate dehydrogenase (GPDH) activity was used as a marker of adipose differentiation; glucose uptake, lipolysis and PAI-1 secretion were measured as parameters of fat cell function.
RESULTS: Human preadipocytes and adipocytes from lean and obese subjects expressed the long leptin receptor isoform and two of the three short forms as assessed by polymerase chain reaction (PCR). Leptin at a supraphysiological concentration induced a transient increase of GPDH activity, but had no effect on glucose uptake and PAI-1 secretion from human adipocytes. In addition, basal and isoproterenol-stimulated lipolysis as well as the antilipolytic action of insulin in human adipocytes was not significantly affected by leptin exposure.
CONCLUSION: In contrast to animal data, the results of our experiments do not demonstrate significant effects of leptin on main metabolic functions of human adipocytes arguing against a local auto-/paracrine action of leptin in human adipose tissue.
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References
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM . Positional cloning of the mouse obese gene and its human homologue Nature 1994 372: 425–432.
Friedman JM, Halaas JC . Leptin and the regulation of body weight in mammals Nature 1998 395: 763–770.
Müller G, Ertl J, Gerl M, Preibisch G . Leptin impairs metabolic actions of insulin in isolated rat adipocytes J Biol Chem 1997 272: 10585–10593.
Mick G, Vanderbloomer T, Ling Fu C, McCormick K . Leptin does not affect adipocytes glucose metabolism: studies in fresh and cultured adipocytes Metabolism 1998 47: 1360–1365.
Zierath JR, Frevert EU, Ryder JW, Berggren PO, Kahn BB . Evidence against a direct effect of leptin on glucose transport in skeletal muscle and adipocytes Diabetes 1998 17: 1–4.
Ranganathan S, Ciaraldi TP, Henry RR, Mudaliar S, Kern PA . Lack of effect of leptin on glucose transport, lipoprotein lipase, and insulin action in adipose and muscle cells Endocrinology 1998 139: 2509–2513.
Frühbeck G, Aguado M, Gomez-Ambrosi J, Martinez JA . Lipolytic effect of in vivo leptin administration on adipocytes of lean and ob/ob mice, but not db/db mice Biochem Biophys Res Commun 1998 250: 99–102.
Marti A, Novo FJ, Martinez-Anso E, Zaratiegui M, Aguado M, Martinez JA . Leptin gene transfer into muscle increases lipolysis and oxygen consumption in white fat tissue in ob/ob mice Biochem Biophys Res Commun 1998 246: 859–862.
Frühbeck G, Aguado M, Martinez JA . In vitro lipolytic effect of leptin on mouse adipocytes: evidence for a possible autocrine/paracrine role of leptin Biochem Biophys Res Commun 1997 240: 590–594.
Siegrist-Kaiser CA, Pauli V, Juge-Aubry CE, Boss O, Pernin A, Chin WW, Cusin I, Rohner-Jeanrenaud F, Burger AG, Zapf J, Meier CA . Direct effects of leptin on brown and white adipose tissue J Clin Invest 1997 100: 2858–2864.
Zhang HH, Kumar S, Barnett AH, Eggo MC . Intrinsic site-specific differences in the expression of leptin in human adipocytes and its autocrine effects on glucose uptake J Clin Endocrinol Metab 1999 84: 2550–2556.
Hauner H, Entenmann G, Wabitsch M, Gaillard D, Ailhaud G, Negrel R, Pfeiffer EF . Promoting effects of glucocorticoids on the differentiation of human adipocyte precursor cells cultured in a chemically defined medium J Clin Invest 1989 84: 1663–1670.
Gottschling-Zeller H, Birgel M, Scriba D, Blum WF, Hauner H . Depot-specific release of leptin from subcutaneous and omental adipocytes in suspension culture: effect of tumor necrosis factor-α and transforming growth factor-β1 Eur J Endocrinol 1999 141: 436–442.
Glasow A, Haidan A, Hilbers U, Breidert M, Gillespie J, Scherbaum WA, Chrousos GP, Bornstein SR . Expression of ob receptor in normal human adrenals: differential regulation of adrenocortical and adrenomedullary function by leptin J Clin Endocrinol Metab 1998 83: 4459–4466.
Pairault J, Green H . A study of the adipose conversion of suspended 3T3 cells by using glycerophosphate dehydrogenase as differentiation marker Proc Natl Acad Sci USA 1979 76: 5138–5142.
Hauner H, Petruschke T, Russ M, Röhrig K, Eckel J . Effects of tumour necrosis factor alpha (TNFα) on glucose transport and lipid metabolism of newly-differentiated human fat cells in cell culture Diabetologia 1995 38: 764–771.
Hellmer J, Arner P, Lundin A . Automatic luminometric kinetic assay of glycerol for lipolysis studies Anal Biochem 1989 177: 132–137.
Kielar D, Clark JSC, Ciechanowicz A, Kurzawski G, Sulikowski T, Narusewicz M . Leptin receptor isoforms expressed in human adipose tissue Metabolism 1998 47: 844–847.
Morio B, Gachon AM, Boirie Y, Rousset P, Gachon P, Beaufrere B, Ritz P . Lipolysis, fatness, gender and plasma leptin concentrations in healthy, normal-weight subjects Eur J Nutr 1999 38: 14–19.
Alessi MC, Peiretti F, Morange P, Henry M, Nalbone G, Juhan-Vague I . Production of plasminogen activator inhibitor-1 by human adipose tissue: possible link between visceral fat accumulation and vascular disease Diabetes 1997 46: 860–867.
Eriksson P, Reynisdottir S, Lonnqvist F, Stemme V, Hamsten A, Arner P . Adipose tissue secretion of plasminogen activator inhibitor-1 in non-obese and obese individuals Diabetologia 1998 41: 64–71.
Gottschling-Zeller H, Birgel M, Röhrig K, Hauner H . Effect of tumor necrosis factor alpha and transforming growth factor beta-1 on plasminogen activator inhibitor-1 secretion from subcutaneous and omental human fat cells Metabolism 2000 49: 666–671.
De Mitrio V, De Pergola G, Vettor R, Marino R, Sciaraffa M, Pagano C, Scaraggi FA, Di Lorenzo L, Giorgino R . Plasma plasminogen activator inhibitor-I is associated with plasma leptin irrespective of body mass index, body fat mass, and plasma insulin and metabolic parameters in premenopausal women Metabolism 1999 48: 960–964.
Acknowledgements
We wish to thank Professor Dr R Olbrisch and his team from the Department of Plastic Surgery at the Florence Nightingale Hospital Düsseldorf-Kaiserswerth and Professor Dr B Husemann and his team from the Surgical Department of the Dominikus-Krankenhaus, Düsseldorf-Heerdt for their support in obtaining adipose tissue samples. This work was supported by a grant to I A-H from the Eli Lilly International Foundation.
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Aprath-Husmann, I., Röhrig, K., Gottschling-Zeller, H. et al. Effects of leptin on the differentiation and metabolism of human adipocytes. Int J Obes 25, 1465–1470 (2001). https://doi.org/10.1038/sj.ijo.0801737
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DOI: https://doi.org/10.1038/sj.ijo.0801737
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