MC4R-dependent suppression of appetite by bone-derived lipocalin 2
| Autor: | Jonathan Barasch, Ioanna Mosialou, Liyong Deng, Steven Shikhel, Haihong Zong, Wendy K. Chung, Thomas Nicholas, Antonio Maurizi, Jeffrey E. Pessin, Lori M. Zeltser, Patricia Lanzano, Stavroula Kousteni, Kevin W. Williams, Mishaela R. Rubin, Na Luo, Rudolph L. Leibel, Jian-min Liu, Yiru Huang, Richard A. Friedman, Zhenyan He |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Eating Mice 0302 clinical medicine Insulin Secretion Cyclic AMP Glucose homeostasis Homeostasis Insulin media_common Animals Appetite Regulation Blood-Brain Barrier Bone and Bones Female Fibroblast Growth Factor-23 Glucose Hypothalamus Insulin Resistance Lipocalin-2 Neurons Obesity Osteoblasts Paraventricular Hypothalamic Nucleus Receptor Melanocortin Type 4 Thinness Multidisciplinary Melanocortin 4 receptor Melanocortin Osteocalcin Type 4 Receptor medicine.medical_specialty media_common.quotation_subject 030209 endocrinology & metabolism Biology 03 medical and health sciences Insulin resistance Internal medicine medicine Appetite medicine.disease 030104 developmental biology Endocrinology biology.protein Hormone |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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