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

Mosialou, Ioanna ; Shikhel, Steven ; Liu, Jian-Min ; Maurizi, Antonio ; Luo, Na ; He, Zhenyan ; Huang, Yiru ; Zong, Haihong ; Friedman, Richard A ; Barasch, Jonathan ; Lanzano, Patricia ; Deng, Liyong ; Leibel, Rudolph L ; Rubin, Mishaela ; Nickolas, Thomas ; Chung, Wendy ; Zeltser, Lori M ; Williams, Kevin W ; Pessin, Jeffrey E ; Kousteni, Stavroula

Nature (London), 2017-03, Vol.543 (7645), p.385-390 [Periódico revisado por pares]

England: Nature Publishing Group

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Título:
MC4R-dependent suppression of appetite by bone-derived lipocalin 2
Autor: Mosialou, Ioanna ; Shikhel, Steven ; Liu, Jian-Min ; Maurizi, Antonio ; Luo, Na ; He, Zhenyan ; Huang, Yiru ; Zong, Haihong ; Friedman, Richard A ; Barasch, Jonathan ; Lanzano, Patricia ; Deng, Liyong ; Leibel, Rudolph L ; Rubin, Mishaela ; Nickolas, Thomas ; Chung, Wendy ; Zeltser, Lori M ; Williams, Kevin W ; Pessin, Jeffrey E ; Kousteni, Stavroula
Assuntos: Animals ; Appetite ; Appetite (Psychophysiology) ; Appetite Regulation - physiology ; Blood-brain barrier ; Blood-Brain Barrier - metabolism ; Bone and Bones - cytology ; Bone and Bones - metabolism ; Bones ; Cyclic AMP - metabolism ; Eating - physiology ; Expenditures ; Female ; Food ; Glucose ; Glucose - metabolism ; Health aspects ; Homeostasis ; Hormones ; Hypothalamus - cytology ; Hypothalamus - metabolism ; Insulin ; Insulin - metabolism ; Insulin Resistance ; Insulin Secretion ; Lipocalin-2 - metabolism ; Male ; Metabolism ; Mice ; Mutation ; Neurons - metabolism ; Obesity ; Obesity - metabolism ; Osteoblasts - metabolism ; Paraventricular Hypothalamic Nucleus - cytology ; Physiological aspects ; Prevention ; Proteins ; Receptor, Melanocortin, Type 4 - metabolism ; Rodents ; Thinness - metabolism
É parte de: Nature (London), 2017-03, Vol.543 (7645), p.385-390
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Present addresses: Department of Endocrine and Metabolic Diseases, Shanghai Rui-jin Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai 200025, China (J.-M.L.); Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila 67100, Italy (A.M.).
Descrição: 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.
Editor: England: Nature Publishing Group
Idioma: Inglês

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

England: Nature Publishing Group

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