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
Naturejournal_title
Natureauthors
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 Sdoi
10.1038/nature21697subject
Has Abstractpub_date
2017-03-16 00:00:00pages
385-390issue
7645eissn
0028-0836issn
1476-4687pii
nature21697journal_volume
543pub_type
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