Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Paper
  • Published:

Effects of leptin on the differentiation and metabolism of human adipocytes

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. 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.

    Article  CAS  Google Scholar 

  2. Friedman JM, Halaas JC . Leptin and the regulation of body weight in mammals Nature 1998 395: 763–770.

    Article  CAS  Google Scholar 

  3. 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.

    Article  Google Scholar 

  4. 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.

    Article  CAS  Google Scholar 

  5. 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.

    Article  Google Scholar 

  6. 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.

    Article  CAS  Google Scholar 

  7. 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.

    Article  Google Scholar 

  8. 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.

    Article  CAS  Google Scholar 

  9. 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.

    Article  Google Scholar 

  10. 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.

    Article  CAS  Google Scholar 

  11. 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.

    CAS  PubMed  Google Scholar 

  12. 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.

    Article  CAS  Google Scholar 

  13. 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.

    Article  CAS  Google Scholar 

  14. 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.

    CAS  PubMed  Google Scholar 

  15. 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.

    Article  CAS  Google Scholar 

  16. 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.

    Article  CAS  Google Scholar 

  17. Hellmer J, Arner P, Lundin A . Automatic luminometric kinetic assay of glycerol for lipolysis studies Anal Biochem 1989 177: 132–137.

    Article  CAS  Google Scholar 

  18. 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.

    Article  CAS  Google Scholar 

  19. 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.

    Article  CAS  Google Scholar 

  20. 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.

    Article  CAS  Google Scholar 

  21. 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.

    Google Scholar 

  22. 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.

    Article  CAS  Google Scholar 

  23. 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.

    Article  CAS  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to H Hauner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0801737

Keywords

This article is cited by

Search

Quick links