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

Article

关键词: GREEN FLUORESCENT PROTEIN;    INSULIN-RECEPTOR;    BODY-WEIGHT;    ENERGY-BALANCE;    NEURONS;    OSTEOBLASTS;    OBESITY;    EXPRESSION;    MICE;    PROOPIOMELANOCORTIN;   

DOI  :  10.1038/nature21697

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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