MC4R-dependent suppression of appetite by bone-derived lipocalin 2

Ioanna Mosialou, Steven Shikhel, Jian Min Liu, Antonio Maurizi, Na Luo, Zhenyan He, Yiru Huang, Haihong Zong, Richard A. Friedman, Jonathan Barasch, Patricia Lanzano, Liyong Deng, Rudolph L. Leibel, Mishaela Rubin, Thomas Nicholas, Wendy Chung, Lori M. Zeltser, Kevin W. Williams, Jeffrey E. Pessin, Stavroula Kousteni

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

Bone has recently emerged as a pleiotropic endocrine organ that secretes at least two hormones, FGF23 and osteocalcin, which regulate kidney function and glucose homeostasis, respectively. These findings have raised the question of whether other bone-derived hormones exist and what their potential functions are. Here we identify, through molecular and genetic analyses in mice, lipocalin 2 (LCN2) as an osteoblast-enriched, secreted protein. Loss- and gain-of-function experiments in mice demonstrate that osteoblast-derived LCN2 maintains glucose homeostasis by inducing insulin secretion and improves glucose tolerance and insulin sensitivity. In addition, osteoblast-derived LCN2 inhibits food intake. LCN2 crosses the blood-brain barrier, binds to the melanocortin 4 receptor (MC4R) in the paraventricular and ventromedial neurons of the hypothalamus and activates an MC4R-dependent anorexigenic (appetite-suppressing) pathway. These results identify LCN2 as a bone-derived hormone with metabolic regulatory effects, which suppresses appetite in a MC4R-dependent manner, and show that the control of appetite is an endocrine function of bone.

Original languageEnglish (US)
Pages (from-to)385-390
Number of pages6
JournalNature
Volume543
Issue number7645
DOIs
StatePublished - Mar 16 2017

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'MC4R-dependent suppression of appetite by bone-derived lipocalin 2'. Together they form a unique fingerprint.

  • Cite this

    Mosialou, I., Shikhel, S., Liu, J. M., Maurizi, A., Luo, N., He, Z., Huang, Y., Zong, H., Friedman, R. A., Barasch, J., Lanzano, P., Deng, L., Leibel, R. L., Rubin, M., Nicholas, T., Chung, W., Zeltser, L. M., Williams, K. W., Pessin, J. E., & Kousteni, S. (2017). MC4R-dependent suppression of appetite by bone-derived lipocalin 2. Nature, 543(7645), 385-390. https://doi.org/10.1038/nature21697