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:

The Arg 389 Gly β1-adrenergic receptor gene polymorphism and human fat cell lipolysis

Abstract

BACKGROUND: The β1-adrenoceptor is a candidate gene for obesity because of its role in catecholamine-induced energy homeostasis. A common Arg 389 Gly variant polymorphism has been shown in recombinant cells to influence its-coupling properties.

OBJECTIVE: To investigate the effect of the Arg 389 Gly β1-adrenoceptor polymorphism on catecholamine-induced lipolysis in native human fat cells obtained by subcutaneous biopsy.

SUBJECTS: Two-hundred and ninety-eight apparently healthy male and female subjects with a wide variation in body mass index (BMI, 18–60 kg/m2).

MEASURES: The lipolytic sensitivities and maximum lipolytic action of noradrenaline and the selective adrenoceptor agonists dobutamine (β1), terbutaline (β2) and CGP 12177 (β3) were determined in isolated subcutaneous adipocytes and related to β-adrenoceptor radioligand binding parameters.

RESULTS: No differences in the sensitivity or maximum lipolytic capacity of the agonists were found between the genotypes. This was true both when all subjects were analyzed together and when subgroups (lean, obese, men, women) were analyzed separately. Radioligand binding to β1- or β2-adrenoceptors was also similar between genotypes. The polymorphism had no important influence on either BMI or the distribution of obese and non-obese subjects between the genotypes.

CONCLUSION: The distribution of the Arg 389 Gly polymorphism is similar in lean and obese subjects and has no apparent effect on the lipolytic response to β-adrenergic stimulation in native human adipocytes. This suggests, despite the altered coupling properties reported in recombinant cells, that the Arg 386 Gly polymorphism has no important influence on human obesity.

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

Similar content being viewed by others

References

  1. Coughlin SR . Expanding horizons for receptors coupled to G proteins. Diversity and disease. Curr Opin Cell Biol 1994 6: 191–197.

    Article  CAS  PubMed  Google Scholar 

  2. Arner P . Regulation of lipolysis in fat cells Diab Rev 1996 4: 450–463.

    Google Scholar 

  3. Maqbool A, Hall AS, Ball SG, Balmforth AJ . Common polymorphisms of β1-adrenoceptor: identification and rapid screening assay Lancet 1999 353: 897.

    Article  CAS  PubMed  Google Scholar 

  4. Strader CD, Fong TM, Tota MR, Underwood D, Dixon RA . Structure and function of G protein-coupled receptors Ann Rev Biochem 1994 63: 101–132.

    Article  CAS  PubMed  Google Scholar 

  5. Mason DA, Moore JD, Green SA, Liggett SB . A gain-of-function polymorphism in a G-protein coupling domain of the human β1-adrenergic receptor J Biol Chem 1999 274: 12670–12674.

    Article  CAS  PubMed  Google Scholar 

  6. Reynisdottir S, Ellerfeldt K, Wahrenberg H, Lithell H, Arner P . Multiple lipolysis defects in the insulin resistance (metabolic syndrome) J Clin Invest 1994 92: 2590–2599.

    Article  Google Scholar 

  7. Arner P, Hellmér J, Wennlund A, Óstman J, Engfeldt P . Adrenoceptor occupancy in isolated human fat cells and its relationship with lipolysis rate Eur J Pharmacol 1988 146: 45–56.

    Article  CAS  PubMed  Google Scholar 

  8. Kenakin T . Drugs and receptors. An overview of the current state of knowledge. Drugs 1990 40: 666–687.

    Article  CAS  PubMed  Google Scholar 

  9. Scatchard G . The attractions of proteins for small molecules and ions Ann NY Acad Sci 1948 51: 660–672.

    Article  Google Scholar 

  10. Munson P, Rodbard D . LIGAND: a versatile computerized approach for characterization of ligand binding systems Anal Biochem 1980 107: 220–239.

    Article  CAS  PubMed  Google Scholar 

  11. Lönnqvist F, Wahrenberg H, Hellström L, Reynisdottir S, Arner P . Lipolytic catecholamine resistance due to decreased β2-adrenoceptor expression in fat cells J Clin Invest 1992 2175–2186.

  12. Large V, Hellström L, Reynisdottir S, Lönnqvist F, Eriksson P, Lannfelt L, Arner P . Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function J Clin Invest 1997 100: 3005–3013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Tesson F, Charron P, Peuchmaurd M, Nicaud V, Cambien F, Tiret L, Poirier O, Desnos M, Jullieres Y, Amouyel P, Roizes G, Dorent R, Schwartz K, Komajda M . Characterization of a unique genetic variant in the beta1-adrenoceptor gene and evaluation of its role in idiopathic dilated cardiomyopathy. CARDIGENE Group. J Mol Cell Cardiol 1999 31: 1025–1032.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The excellent technical assistance of Britt Marie Leijonhufvud, Katarina Hertel, Eva Sjölin and Kerstin Wåhlen is greatly appreciated. This study was supported by grants from Swedish Medical Research, Novo Nordic Foundation, Swedish Diabetes Association, Swedish Heart and Lung Foundation, the foundations of Söderberg and Thuring and Swedish Society of Medicine.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to P Arner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rydén, M., Hoffstedt, J., Eriksson, P. et al. The Arg 389 Gly β1-adrenergic receptor gene polymorphism and human fat cell lipolysis. Int J Obes 25, 1599–1603 (2001). https://doi.org/10.1038/sj.ijo.0801815

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0801815

Keywords

This article is cited by

Search

Quick links