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.

  • Original Article
  • Published:

Increased expression of hypothalamic leptin receptor and adiponectin accompany resistance to dietary-induced obesity and infertility in female C57BL/6J mice

International Journal of Obesity volume 31, pages 395–402 (2007)Cite this article

Abstract

Background:

Obesity is strongly associated with female infertility, but the mechanisms underlying this relationship are largely unknown.

Methods:

We investigated the effect of increasing dietary fat percentage upon body mass, hypothalamic neuropeptide gene expression, adipose hormone secretion and fertility in females of the inbred mouse strains C57BL/6J and DBA/2J. To assess the effect of obesity independent of dietary influence, we also compared these parameters in wild-type female C57BL/6J mice to those congenic for the obesogenic mutations ob/ob and Ay/a.

Results:

After 24 weeks, rather than exhibiting an obese, leptin-resistant phenotype like their female DBA/2J counterparts, wild-type female C57BL/6J mice remained lean, fertile and manifested increased hypothalamic LEPR-B expression. Although both mutant genotypes were associated with obesity and subfertility, ob/ob mice demonstrated significantly increased hypothalamic LEPR-B expression, whereas Ay/a mice had a significant reduction. Interestingly, wild-type female C57BL/6J mice were noted to manifest significantly higher and lower levels of adiponectin and tissue plasminogen activator inhibitor-1 (tPAI-1), respectively, than weight-matched wild-type female DBA/2J mice.

Conclusions:

We conclude that (1) resistance to the obese-infertile phenotype in female C57BL/6J mice is associated with increased hypothalamic leptin receptor expression and alterations in adipokine levels consistent with decreased adipose tissue inflammation and (2) that long-standing hyperleptinemic obesity in mice is associated with a downregulation of the hypothalamic leptin receptor.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. Frederich RC, Lollmann B, Hamann A, Napolitano-Rosen A, Kahn BB, Lowell BB et al. Expression of ob mRNA and its encoded protein in rodents. Impact of nutrition and obesity. J Clin Invest 1995; 96: 1658–1663.

    Article  CAS  Google Scholar 

  2. Frederich RC, Hamann A, Anderson S, Lollmann B, Lowell BB, Flier JS . Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action. Nat Med 1995; 1: 1311–1314.

    Article  CAS  Google Scholar 

  3. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996; 334: 292–295.

    Article  CAS  Google Scholar 

  4. Carlsson B, Lindell K, Gabrielsson B, Karlsson C, Bjarnason R, Westphal O et al. Obese (ob) gene defects are rare in human obesity. Obes Res 1997; 5: 30–35.

    Article  CAS  Google Scholar 

  5. Fantuzzi G . Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 2005; 115: 911–919; quiz 920.

    Article  CAS  Google Scholar 

  6. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante Jr W . Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003; 112: 1796–1808.

    Article  CAS  Google Scholar 

  7. Tortoriello DV, McMinn J, Chua SC . Dietary-induced obesity and hypothalamic infertility in female DBA/2J mice. Endocrinology 2004; 145: 1238–1247.

    Article  CAS  Google Scholar 

  8. Lansang MC, Williams GH, Carroll JS . Correlation between the glucose clamp technique and the homeostasis model assessment in hypertension. Am J Hypertens 2001; 14: 51–53.

    Article  CAS  Google Scholar 

  9. Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 2000; 85: 2402–2410.

    Article  CAS  Google Scholar 

  10. El-Haschimi K, Lehnert H . Leptin resistance – or why leptin fails to work in obesity. Exp Clin Endocrinol Diabetes 2003; 111: 2–7.

    Article  CAS  Google Scholar 

  11. Huang XF, Han M, South T, Storlien L . Altered levels of POMC, AgRP and MC4-R mRNA expression in the hypothalamus and other parts of the limbic system of mice prone or resistant to chronic high-energy diet-induced obesity. Brain Res 2003; 992: 9–19.

    Article  CAS  Google Scholar 

  12. Huang XF, Han M, Storlien LH . The level of NPY receptor mRNA expression in diet-induced obese and resistant mice. Brain Res Mol Brain Res 2003; 115: 21–28.

    Article  CAS  Google Scholar 

  13. Ravinet Trillou C, Arnone M, Delgorge C, Gonalons N, Keane P, Maffrand JP et al. Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice. Am J Physiol Regul Integr Comp Physiol 2003; 284: R345–R353.

    Article  Google Scholar 

  14. Lin S, Storlien LH, Huang XF . Leptin receptor, NPY, POMC mRNA expression in the diet-induced obese mouse brain. Brain Res 2000; 875: 89–95.

    Article  CAS  Google Scholar 

  15. Agardh CD, Agardh E, Hultberg B, Ahren B . Long-standing hyperglycemia in C57BL/6J mice does not affect retinal glutathione levels or endothelial/pericyte ratio in retinal capillaries. J Diabetes Complications 2000; 14: 146–153.

    Article  CAS  Google Scholar 

  16. De Taeye B, Smith LH, Vaughan DE . Plasminogen activator inhibitor-1: a common denominator in obesity, diabetes and cardiovascular disease. Curr Opin Pharmacol 2005; 5: 149–154.

    Article  CAS  Google Scholar 

  17. Fay WP, Shapiro AD, Shih JL, Schleef RR, Ginsburg D . Brief report: complete deficiency of plasminogen-activator inhibitor type 1 due to a frame-shift mutation. N Engl J Med 1992; 327: 1729–1733.

    Article  CAS  Google Scholar 

  18. Chorostowska-Wynimko J, Skrzypczak-Jankun E, Jankun J . Plasminogen activator inhibitor type-1 controls the process of the in vitro sprout formation. J Physiol Pharmacol 2004; 55 (Suppl 3): 49–56.

    PubMed  Google Scholar 

  19. Ma LJ, Mao SL, Taylor KL, Kanjanabuch T, Guan Y, Zhang Y et al. Prevention of obesity and insulin resistance in mice lacking plasminogen activator inhibitor 1. Diabetes 2004; 53: 336–346.

    Article  CAS  Google Scholar 

  20. Kadowaki T, Yamauchi T . Adiponectin and adiponectin receptors. Endocr Rev 2005; 26: 439–451.

    Article  CAS  Google Scholar 

  21. Yamauchi T, Kamon J, Waki H, Murakami K, Motojima K, Komeda K et al. The mechanisms by which both heterozygous peroxisome proliferator-activated receptor gamma (PPARgamma) deficiency and PPARgamma agonist improve insulin resistance. J Biol Chem 2001; 276: 41245–41254.

    Article  CAS  Google Scholar 

  22. Qi Y, Takahashi N, Hileman SM, Patel HR, Berg AH, Pajvani UB et al. Adiponectin acts in the brain to decrease body weight. Nat Med 2004; 10: 524–529.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work has been supported by a Women's Reproductive Health Research Scholarship, NIH 5 K12 HD001275 (DVT).

Author information

Authors and Affiliations

  1. Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Columbia University, New York, NY, USA

    D V Tortoriello

  2. Division of Molecular Genetics, Department of Pediatrics, Columbia University, New York, NY, USA

    J E McMinn

  3. Departments of Medicine and Neuroscience, Albert Einstein College of Medicine, New York, NY, USA

    S C Chua

Authors
  1. D V Tortoriello
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J E McMinn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S C Chua
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D V Tortoriello.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tortoriello, D., McMinn, J. & Chua, S. Increased expression of hypothalamic leptin receptor and adiponectin accompany resistance to dietary-induced obesity and infertility in female C57BL/6J mice. Int J Obes 31, 395–402 (2007). https://doi.org/10.1038/sj.ijo.0803392

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0803392

Keywords

This article is cited by

Search

Advanced search

Quick links