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.

Role of leptin in the neuroendocrine response to fasting

Abstract

A TOTAL deficiency in or resistance to the protein leptin causes severe obesity1–4. As leptin levels rise with increasing adiposity in rodents5 and man6,7, it is proposed to act as a negative feedback 'adipostatic signal' to brain centres controlling energy homeostasis, limiting obesity in times of nutritional abundance1,3. Starvation is also a threat to homeostasis that triggers adaptive responses8–12, but whether leptin plays a role in the physiology of starvation is unknown. Leptin concentration falls during starvation13 and totally leptin-deficient ob/ob mice have neuroendocrine abnormalities similar to those of starvation14, suggesting that this may be the case. Here we show that preventing the starvation-induced fall in leptin with exogenous leptin substantially blunts the changes in gonadal, adrenal and thyroid axes in male mice, and prevents the starvation-induced delay in ovulation in female mice. In contrast, leptin repletion during this period of starvation has little or no effect on body weight, blood glucose or ketones. We propose that regulation of the neuroendocrine system during starvation could be the main physiological role of leptin.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

References

  1. Zhang, Y. et al. Nature 372, 425–432 (1994).

    ADS  CAS  Article  Google Scholar 

  2. Halaas, J. L. et al. Science 269, 543–546 (1995).

    ADS  CAS  Article  Google Scholar 

  3. Campfield, L. A. et al. Science 269, 546–549 (1995).

    ADS  CAS  Article  Google Scholar 

  4. Stephens, T. W. et al. Nature 377, 530–532 (1995).

    ADS  CAS  Article  Google Scholar 

  5. Frederich, R. C. et al. Nature Med. 1, 1311–1314 (1995).

    CAS  Article  Google Scholar 

  6. Maffei, M. et al. Nature Med. 1, 1155–1161 (1995).

    CAS  Article  Google Scholar 

  7. Considine, R. V. et al. N. Engl. J. Med. 334, 292–295 (1996).

    CAS  Article  Google Scholar 

  8. Cahill, J. G. et al. J. clin. Invest. 45, 1751–1769 (1966).

    CAS  Article  Google Scholar 

  9. Schwartz, M. W., Dallman, M. F. & Woods, S. C. Am. J. Physiol. 269, R949–R957 (1995).

    CAS  PubMed  Google Scholar 

  10. Dallman, M. F. et al. Front. Neuroendocr. 14, 303–347 (1993).

    CAS  Article  Google Scholar 

  11. Bronson, F. H. & Marstellar, F. Biol. Reprod. 33, 660–667 (1985).

    CAS  Article  Google Scholar 

  12. Connors, J. M. et al. Endocrinology 117, 900–906 (1985).

    CAS  Article  Google Scholar 

  13. Frederich, R. C. et al. J. clin. Invest. 96, 1658–1663 (1995).

    CAS  Article  Google Scholar 

  14. Bray, G. A., Fisler, J. & York, D. A. Front. Neuroendocr. 14, 128–181 (1990).

    Google Scholar 

  15. Schreihofer, D. A., Amico, J. A. & Cameron, J. L. Endocrinology 132, 1890–1897 (1993).

    CAS  Article  Google Scholar 

  16. Bates, G. M. Clin. Obstet. Gynec. 28, 632–644 (1985).

    CAS  Article  Google Scholar 

  17. Tartaglia, L. A. et al. Cell 83, 1263–1271 (1995).

    CAS  Article  Google Scholar 

  18. Lee, G.-H. et al. Nature 379, 632–635 (1996).

    ADS  CAS  Article  Google Scholar 

  19. White, J. D. & Kershaw, M. Molec. cell. Neurosci. 1, 41–48 (1989).

    Article  Google Scholar 

  20. Pierroz, D. Q. et al. Endocrinology 137, 3–12 (1996).

    CAS  Article  Google Scholar 

  21. Chebab, F. F., Lim, M. E. & Lu, R. Nature Genet. 12, 318–320 (1996).

    Article  Google Scholar 

  22. Erickson, J. C., Clegg, K. E. & Palmiter, R. D. Nature 381, 415–418 (1996).

    ADS  CAS  Article  Google Scholar 

  23. Cooper, R. L. et al. Endocrinology 114, 391–396 (1984).

    CAS  Article  Google Scholar 

  24. Qu, D. et al. Nature 380, 243–247 (1996).

    ADS  CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ahima, R., Prabakaran, D., Mantzoros, C. et al. Role of leptin in the neuroendocrine response to fasting. Nature 382, 250–252 (1996). https://doi.org/10.1038/382250a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/382250a0

Further reading

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