title: AgRP Neurons Regulate Bone Mass.
abstract: The hypothalamus has been implicated in skeletal metabolism. Whether hunger-promoting neurons of the arcuate nucleus impact the bone is not known. We generated multiple lines of mice to affect AgRP neuronal circuit integrity. We found that mice with Ucp2 gene deletion, in which AgRP neuronal function was impaired, were osteopenic. This phenotype was rescued by cell-selective reactivation of Ucp2 in AgRP neurons. When the AgRP circuitry was impaired by early postnatal deletion of AgRP neurons or by cell autonomous deletion of Sirt1 (AgRP-Sirt1(-/-)), mice also developed reduced bone mass. No impact of leptin receptor deletion in AgRP neurons was found on bone homeostasis. Suppression of sympathetic tone in AgRP-Sirt1(-/-) mice reversed osteopenia in transgenic animals. Taken together, these observations establish a significant regulatory role for AgRP neurons in skeletal bone metabolism independent of leptin action.
authors.affiliation: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 406-772, Republic of Korea.
authors.forename: Jae Geun
authors.initials: JG
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Ben-Hua
authors.initials: BH
authors.lastname: Sun
authors.affiliation: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre RS 90035, Brazil.
authors.forename: Marcelo O
authors.initials: MO
authors.lastname: Dietrich
authors.affiliation: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Institute of Anatomy, University of Leipzig, 04103 Leipzig, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Koch
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Gang-Qing
authors.initials: GQ
authors.lastname: Yao
authors.affiliation: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Diano
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Insogna
authors.affiliation: Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: tamas.horvath@yale.edu.
authors.forename: Tamas L
authors.initials: TL
authors.lastname: Horvath
mesh_terms: D054369:Agouti-Related Protein / Q000172:deficiency / Q000235:genetics*; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015519:Bone Density / Q000187:drug effects*; D001851:Bone Diseases, Metabolic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005269:Femur / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006706:Homeostasis; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007473:Ion Channels / Q000172:deficiency / Q000235:genetics; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000172:deficiency / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009638:Norepinephrine / Q000378:metabolism; D010641:Phenotype; D011433:Propranolol / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000172:deficiency / Q000235:genetics; D013977:Tibia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000071246:Uncoupling Protein 2
chemical_list: D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D007473:Ion Channels; D020738:Leptin; D024101:Mitochondrial Proteins; D011943:Receptors, Adrenergic, beta; D054411:Receptors, Leptin; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D011433:Propranolol; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D009638:Norepinephrine