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

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.

journal_name

Nature

journal_title

Nature

authors

Mosialou I,Shikhel S,Liu JM,Maurizi A,Luo N,He Z,Huang Y,Zong H,Friedman RA,Barasch J,Lanzano P,Deng L,Leibel RL,Rubin M,Nickolas T,Chung W,Zeltser LM,Williams KW,Pessin JE,Kousteni S

doi

10.1038/nature21697

subject

Has Abstract

pub_date

2017-03-16 00:00:00

pages

385-390

issue

7645

eissn

0028-0836

issn

1476-4687

pii

nature21697

journal_volume

543

pub_type

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