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.

  • Letter
  • Published:

Atypical β-adrenoceptor on brown adipocytes as target for anti-obesity drugs

Abstract

Recent studies suggest that thermogenesis in brown adipose tissue has an important role in the regulation of energy balance1–7. Thermogenesis is effected by noradrenaline released from sympathetic nerve endings; the noradrenaline stimulates β;-adrenoceptors, causing lipolysis, and the released fatty acids then promote the uncoupling of oxidative phosphorylation from electron transport8,9. It has been widely accepted10–13 that mammalian β-adrenoceptors exist as two subtypes, β1 and β2 (ref. 14), and rat brown adipocyte β-adrenoceptors have been classed as β1 (refs 15–17) or as a mixed β1/β2 population18. The β1 subtype predominates in atria, whereas the β2 subtype predominates in trachea. However, we have now found a novel group of β-adrenoceptor agonists that selectively stimulate lipolysis in brown adipocytes. In contrast, isoprenaline, fenoterol and salbutamol are less potent as stimulants of lipolysis than as stimulants of atrial rate or tracheal relaxation. Therefore, β-adrenoceptors in rat brown adipocytes are of neither the β1 nor β2 subtypes. Compounds that selectively stimulate brown adipocyte β-adrenoceptors should have potential as thermogenic anti-obesity agents and this has been demonstrated with BRL 26830A, BRL 33725A and BRL 35135A.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Similar content being viewed by others

References

  1. Rothwell, N. J. & Stock, M. J. Nature 281, 31–35 (1979).

    Article  ADS  CAS  Google Scholar 

  2. Rothwell, N. J. & Stock, M. J. Pflügers Arch. ges. Physiol. 389, 237–242 (1981).

    Article  CAS  Google Scholar 

  3. Thurlby, P. L. & Trayhurn, P. Pflügers Arch. ges. Physiol. 385, 193–201 (1980).

    Article  CAS  Google Scholar 

  4. Trayhurn, P., Jones, P. M., McGuckin, M. M. & Goodbody, A. E. Nature 295, 323–325 (1982).

    Article  ADS  CAS  Google Scholar 

  5. Wickler, S. J., Horwitz, B. A. & Stern, J. S. Int. J. Obesity 6, 481–490 (1982).

    CAS  Google Scholar 

  6. Seydoux, J., Rohner-Jeanrenaud, F., Assimacopoulos-Jeannet, F., Jeanrenaud, B. & Girardier, L. Pflügers Arch. ges. Physiol. 390, 1–4 (1981).

    Article  CAS  Google Scholar 

  7. Connolly, E., Morrisey, R. D. & Carnie, J. A. Br. J. Nutr. 47, 653–658 (1982).

    Article  CAS  Google Scholar 

  8. Bukowiecki, L. J., Folléa, N., Lupien, J. & Paradis, A. J. biol. Chem. 256, 12840–12848 (1981).

    CAS  PubMed  Google Scholar 

  9. Locke, R. M., Rial, E., Scott, I. D. & Nicholls, D. G. Eur. J. Biochem. 129, 373–380 (1982).

    Article  CAS  Google Scholar 

  10. Arnold, A. Trends pharmac. Sci. 3, 7 (1982).

    Article  CAS  Google Scholar 

  11. Daly, M. J. & Levy, G. P. Trends Autonomic Pharmac. 1, 347–385 (1979).

    CAS  Google Scholar 

  12. Minneman, K. P., Pittman, R. M. & Molinoff, P. B. A. Rev. Neurosci. 4, 419–461 (1981).

    Article  CAS  Google Scholar 

  13. Nahorski, S. R. Trends pharmac. Sci. 2, 95–98 (1981).

    Article  CAS  Google Scholar 

  14. Lands, A. M., Arnold, A., McAuliff, J. P., Luduena, F. P. & Brown, T. G. Jr. Nature 214, 597–598 (1967).

    Article  ADS  CAS  Google Scholar 

  15. Bukowiecki, L., Folléa, N., Vallieres, J. & LeBlanc, J. Eur. J. Biochem. 92, 189–196 (1978).

    Article  CAS  Google Scholar 

  16. Svoboda, P., Svartengren, J., Snochowski, M., Houštěk, J. & Cannon, B. Eur. J. Biochem 102, 203–2101979).

    Article  CAS  Google Scholar 

  17. Bukowieki, L., Folléa, N., Paradis, A. & Collet, A. Am. J. Physiol. 238, E552–563 (1980).

    Google Scholar 

  18. Rothwell, N. J., Stock, M. J. & Stribling, D. Pharmac. Ther. 17, 251–268 (1982).

    Article  CAS  Google Scholar 

  19. Furchgott, R. F. in Catecholamines (eds Blaschko, H. & Muscholl, E.) 286–335 (Springer, Berlin, 1972).

    Google Scholar 

  20. Wilson, C., Wilson, S., Piercy, V., Sennitt, M. V. & Arch, J. R. S. Eur. J. Pharmac. (in the press).

  21. O'Donnell, S. R. Eur. J. Pharmac. 19, 371–379 (1972).

    Article  CAS  Google Scholar 

  22. Kenakin, T. P. & Beek, D. J. Pharmac. exp. Ther. 213, 406–413 (1980).

    CAS  Google Scholar 

  23. MacKay, D. J. Pharm. Pharmac. 30, 312–313 (1978).

    Article  CAS  Google Scholar 

  24. Arch, J. R. S. et al. Int. J. Obesity (in the press).

  25. Heaton, G. M., Wagenvoord, R. J., Kemp, A. & Nicholls, D. G. Eur. J. Biochem. 82, 515–521 (1978).

    Article  CAS  Google Scholar 

  26. Desautels, M., Zaror-Behrens, G. & Himms-Hagen, J. Can. J. Biochem. 56, 378–383 (1978).

    Article  CAS  Google Scholar 

  27. Arch, J. R. S. & Ainsworth, A. T. Am. J. clin. Nutr. 38, 549–558 (1983).

    Article  CAS  Google Scholar 

  28. Harms, H. H., Zaagsma, J. & van der Wal, B. Eur. J. Pharmac. 25, 87–91 (1974).

    Article  CAS  Google Scholar 

  29. De Vente, J., Bast, A. van Bree, L. & Zaagsma, J. Eur. J. Pharmac. 63, 73–83 (1980).

    Article  CAS  Google Scholar 

  30. Tan, S. & Curtis-Prior, P. B. Int. J. Obesity 7, 409–414 (1983).

    CAS  Google Scholar 

  31. Bojanic, D., Jansen, J. D., Nahorski, S. R. & Zaagsma, J. Br. J. Pharmac. 81, Suppl. 4P (1984).

  32. Van Rossum, J. M. Archs int. Pharmacodyn. 143, 299–330 (1963).

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Arch, J., Ainsworth, A., Cawthorne, M. et al. Atypical β-adrenoceptor on brown adipocytes as target for anti-obesity drugs. Nature 309, 163–165 (1984). https://doi.org/10.1038/309163a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/309163a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing