title: Oxytocin reverses ovariectomy-induced osteopenia and body fat gain.
abstract: Osteoporosis and overweight/obesity constitute major worldwide public health burdens that are associated with aging. A high proportion of women develop osteoporosis and increased intraabdominal adiposity after menopause. which leads to bone fractures and metabolic disorders. There is no efficient treatment without major side effects for these 2 diseases. We previously showed that the administration of oxytocin (OT) normalizes ovariectomy-induced osteopenia and bone marrow adiposity in mice. Ovariectomized mice, used as an animal model mimicking menopause, were treated with OT or vehicle. Trabecular bone parameters and fat mass were analyzed using micro-computed tomography. Herein, we show that this effect on trabecular bone parameters was mediated through the restoration of osteoblast/osteoclast cross talk via the receptor activator of nuclear factor-κB ligand /osteoprotegerin axis. Moreover, the daily administration of OT normalized body weight and intraabdominal fat depots in ovariectomized mice. Intraabdominal fat mass is more sensitive to OT that sc fat depots, and this inhibitory effect is mediated through inhibition of adipocyte precursor's differentiation with a tendency to lower adipocyte size. OT treatment did not affect food intake, locomotors activity, or energy expenditure, but it did promote a shift in fuel utilization favoring lipid oxidation. In addition, the decrease in fat mass resulted from the inhibition of the adipose precursor's differentiation. Thus, OT constitutes an effective strategy for targeting osteopenia, overweight, and fat mass redistribution without any detrimental effects in a mouse model mimicking the menopause.
authors: University of Nice Sophia Antipolis (G.E.B., D.F.P., M.D., G.A., E.-Z.A.) and Centre National de la Recherche Scientifique (CNRS) (G.B., D.F.P., M.D., G.A., E.-Z.A.), Institut de Biologie Valrose (iBV), Unite Mixte de Recherché (UMR) 7277, 06100 Nice, France; Institut National de la Sante et de la Recherche Medicale (INSERM) (G.E.B., D.F.P., M.D., G.A., E.-Z.A.), iBV, U1091, 06100 Nice, France; University of Paris Diderot (J.C., S.L.), Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative (BFA) UMR 8251, CNRS, F-75205 Paris, France; University of Nantes (S.B., J.A., D.H.), INSERM, UMR 957, Nantes, Equipe Labellisée Ligue Contre le Cancer 2012, France; Graftys SA (F.B.), Aix-en-Provence, France; University of Nice Sophia Antipolis (J.-F.M.), Unite de Formation et de Recherche Médecine, Nice, France F-06189; and Anatomopathology Service (J.-F.M.), Pasteur Hospital, Centre Hospitalier Universitaire de Nice, Nice, France.
authors: Guillaume E
authors: GE
authors: Beranger
authors: Didier F
authors: DF
authors: Pisani
authors: Julien
authors: J
authors: Castel
authors: Mansour
authors: M
authors: Djedaini
authors: Séverine
authors: S
authors: Battaglia
authors: Jérôme
authors: J
authors: Amiaud
authors: Florian
authors: F
authors: Boukhechba
authors: Gérard
authors: G
authors: Ailhaud
authors: Jean-François
authors: JF
authors: Michiels
authors: Dominique
authors: D
authors: Heymann
authors: Serge
authors: S
authors: Luquet
authors: Ez-Zoubir
authors: EZ
authors: Amri
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D001851:Bone Diseases, Metabolic / Q000188:drug therapy* / Q000378:metabolism; D018929:Cell Culture Techniques; D018920:Coculture Techniques; D004195:Disease Models, Animal; D005260:Female; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000737:chemistry; D008593:Menopause / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D010024:Osteoporosis / Q000378:metabolism; D010052:Ovariectomy; D010100:Oxygen / Q000737:chemistry; D010121:Oxytocin / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects*; D055114:X-Ray Microtomography
chemical_list: D020738:Leptin; D008055:Lipids; D010121:Oxytocin; D010100:Oxygen