MC4R-dependent suppression of appetite by bone-derived lipocalin 2.
MC4R-dependent suppression of appetite by bone-derived lipocalin 2.
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DOI：
10.1038/nature21697
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发表时间：
2017-03-16
期刊：
影响因子：
64.8
通讯作者：
Kousteni S
中科院分区：
文献类型：
--
作者：
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
骨是一种多效内分泌器官，可分泌至少两种激素，FGF 23和骨钙素，分别调节肾功能和葡萄糖稳态。这些发现提出了是否存在其他骨源性激素以及它们的潜在功能的问题。在这里，我们确定，通过在小鼠中的分子和遗传分析，脂质运载蛋白2（LCN 2）作为成骨细胞富集，分泌蛋白。小鼠功能丧失和获得实验表明，成骨细胞衍生的LCN 2通过诱导胰岛素分泌维持葡萄糖稳态，并改善葡萄糖耐量和胰岛素敏感性。此外，成骨细胞衍生的LCN 2抑制食物摄入。LCN 2穿过血脑屏障，与下丘脑的室旁和腹内侧神经元中的黑皮质素4受体（MC4R）结合，并激活MC4R依赖性食欲抑制（食欲抑制）途径。这些结果确定LCN 2是一种具有代谢调节作用的骨源性激素，它以MC 4 R依赖性方式抑制食欲，并表明食欲的控制是骨骼的内分泌功能。
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.
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影响因子：
7.7
作者：
Guo H;Jin D;Zhang Y;Wright W;Bazuine M;Brockman DA;Bernlohr DA;Chen X
通讯作者：
Chen X
影响因子：
64.5
作者：
Ferron M;Wei J;Yoshizawa T;Del Fattore A;DePinho RA;Teti A;Ducy P;Karsenty G
通讯作者：
Karsenty G
影响因子：
15.9
作者：
Kode, Aruna;Mosialou, Ioanna;Kousteni, Stavroula
通讯作者：
Kousteni, Stavroula
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
29
作者：
Eguchi J;Wang X;Yu S;Kershaw EE;Chiu PC;Dushay J;Estall JL;Klein U;Maratos-Flier E;Rosen ED
通讯作者：
Rosen ED