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.

  • Short Communication
  • Published:

Leptin administration in physiological or pharmacological doses does not alter circulating irisin levels in humans

International Journal of Obesity volume 40, pages 1461–1463 (2016)Cite this article

Subjects

Abstract

Leptin is an adipokine causing browning of adipose tissue, and it thus increases energy expenditure. The same is true for irisin. We studied whether exogenously administered metreleptin affects serum irisin concentrations in humans, which would suggest a direct interplay between leptin and irisin. We performed two studies: a dose-escalating 1-day-long study and a randomized placebo-controlled study. Study 1: 15 healthy, normal-weight and/or obese male and female individuals participated in three 1-day-long trials of metreleptin administration in the fed state. Metreleptin was administered once at physiological and pharmacological (0.01, 0.1 and 0.3 mg per kg body weight) doses. Study 2: 18 apparently healthy hypoleptinemic young women with hypoleptinemia and secondary amenorrhea took part in this study. Subjects received either metreleptin in replacement doses (0.08 and/or 0.12 mg kg−1) or placebo for 16 weeks. Blood samples were analyzed for leptin and irisin. We found no effect of metreleptin administration on irisin levels of subjects studied at either the fasting or the fed state either in the short or the long term. We provide evidence that leptin is not altering circulating irisin levels in humans.

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

Similar content being viewed by others

References

  1. Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC et al. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012; 481: 463–468.

    Article  Google Scholar 

  2. Roca-Rivada A, Castelao C, Senin LL, Landrove MO, Baltar J, Belen Crujeiras A et al. FNDC5/irisin is not only a myokine but also an adipokine. PLoS One 2013; 8: e60563.

    Article  CAS  Google Scholar 

  3. Gutierrez-Repiso C, Garcia-Serrano S, Rodriguez-Pacheco F, Garcia-Escobar E, Haro-Mora JJ, Garcia-Arnes J et al. FNDC5 could be regulated by leptin in adipose tissue. Eur J Clin Invest 2014; 44: 918–925.

    Article  CAS  Google Scholar 

  4. Swick AG, Orena S, O'Connor A . Irisin levels correlate with energy expenditure in a subgroup of humans with energy expenditure greater than predicted by fat free mass. Metabolism 2013; 62: 1070–1073.

    Article  CAS  Google Scholar 

  5. Panagiotou G, Mu L, Na B, Mukamal KJ, Mantzoros CS . Circulating irisin, omentin-1, and lipoprotein subparticles in adults at higher cardiovascular risk. Metabolism 2014; 63: 1265–1271.

    Article  CAS  Google Scholar 

  6. Rezai-Zadeh K, Yu S, Jiang Y, Laque A, Schwartzenburg C, Morrison CD et al. Leptin receptor neurons in the dorsomedial hypothalamus are key regulators of energy expenditure and body weight, but not food intake. Mol Metab 2014; 3: 681–693.

    Article  CAS  Google Scholar 

  7. Zhang Y, Li R, Meng Y, Li S, Donelan W, Zhao Y et al. Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling. Diabetes 2014; 63: 514–525.

    Article  CAS  Google Scholar 

  8. Chan JL, Wong SL, Mantzoros CS . Pharmacokinetics of subcutaneous recombinant methionyl human leptin administration in healthy subjects in the fed and fasting states: regulation by gender and adiposity. Clin Pharm 2008; 47: 753–764.

    Article  CAS  Google Scholar 

  9. Chou SH, Chamberland JP, Liu X, Matarese G, Gao C, Stefanakis R et al. Leptin is an effective treatment for hypothalamic amenorrhea. Proc Natl Acad Sci USA 2011; 108: 6585–6590.

    Article  CAS  Google Scholar 

  10. Park KH, Zaichenko L, Brinkoetter M, Thakkar B, Sahin-Efe A, Joung KE et al. Circulating irisin in relation to insulin resistance and the metabolic syndrome. J Clin Endocrinol Metab 2013; 98: 4899–4907.

    Article  CAS  Google Scholar 

  11. Loffler D, Muller U, Scheuermann K, Friebe D, Gesing J, Bielitz J et al. Serum irisin levels are regulated by acute strenuous exercise. J Clin Endocrinol Metab 2015; 100: 1289–1299.

    Article  Google Scholar 

  12. Mantzoros CS, Frederich RC, Qu D, Lowell BB, Maratos-Flier E, Flier JS . Severe leptin resistance in brown fat-deficient uncoupling protein promoter-driven diphtheria toxin A mice despite suppression of hypothalamic neuropeptide Y and circulating corticosterone concentrations. Diabetes 1998; 47: 230–238.

    Article  CAS  Google Scholar 

  13. Elsen M, Raschke S, Eckel J . Browning of white fat: does irisin play a role in humans? J Endocrinol 2014; 222: R25–R38.

    Article  CAS  Google Scholar 

  14. Lee P, Linderman JD, Smith S, Brychta RJ, Wang J, Idelson C et al. Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metab 2014; 19: 302–309.

    Article  CAS  Google Scholar 

  15. Shan T, Liang X, Bi P, Kuang S . Myostatin knockout drives browning of white adipose tissue through activating the AMPK-PGC1alpha-Fndc5 pathway in muscle. FASEB J 2013; 27: 1981–1989.

    Article  CAS  Google Scholar 

  16. Rodriguez A, Becerril S, Mendez-Gimenez L, Ramirez B, Sainz N, Catalan V et al. Leptin administration activates irisin-induced myogenesis via nitric oxide-dependent mechanisms, but reduces its effect on subcutaneous fat browning in mice. Int J Obes (Lond) 2015; 39: 397–407.

    Article  CAS  Google Scholar 

  17. Palacios-Gonzalez B, Vadillo-Ortega F, Polo-Oteyza E, Sanchez T, Ancira-Moreno M, Romero-Hidalgo S et al. Irisin levels before and after physical activity among school-age children with different BMI: a direct relation with leptin. Obesity (Silver Spring) 2015; 23: 729–732.

    Article  CAS  Google Scholar 

  18. Bluher S, Panagiotou G, Petroff D, Markert J, Wagner A, Klemm T et al. Effects of a 1-year exercise and lifestyle intervention on irisin, adipokines, and inflammatory markers in obese children. Obesity (Silver Spring) 2014; 22: 1701–1708.

    Article  Google Scholar 

Download references

Acknowledgements

This study was funded by the Institutional BIDMC. The project was also supported by Harvard Clinical and Translational Science Center Grant UL1 RR025758 from the National Center for Research Resources.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    A Gavrieli, G Panagiotou & C S Mantzoros

Authors
  1. A Gavrieli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G Panagiotou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C S Mantzoros
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C S Mantzoros.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gavrieli, A., Panagiotou, G. & Mantzoros, C. Leptin administration in physiological or pharmacological doses does not alter circulating irisin levels in humans. Int J Obes 40, 1461–1463 (2016). https://doi.org/10.1038/ijo.2016.99

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2016.99

This article is cited by

Search

Advanced search

Quick links