| First Author | Mosialou I | Year | 2017 |
| Journal | Nature | Volume | 543 |
| Issue | 7645 | Pages | 385-390 |
| PubMed ID | 28273060 | Mgi Jnum | J:246580 |
| Mgi Id | MGI:5924636 | Doi | 10.1038/nature21697 |
| Citation | Mosialou I, et al. (2017) MC4R-dependent suppression of appetite by bone-derived lipocalin 2. Nature 543(7645):385-390 |
| abstractText | 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. |
