title: Oxytocin receptor in the hypothalamus is sufficient to rescue normal thermoregulatory function in male oxytocin receptor knockout mice.
abstract: Oxytocin (OXT) and OXT receptor (OXTR) have been implicated in the regulation of energy homeostasis, but the detailed mechanism is still unclear. We recently showed late-onset obesity and impaired cold-induced thermogenesis in male OXTR knockout (Oxtr(-/-)) mice. Here we demonstrate that the OXTR in the hypothalamus has important functions in thermoregulation. Male Oxtr(-/-) mice failed to maintain their body temperatures during exposure to a cold environment. Oxtr(-/-) mice also showed decreased neuronal activation in the thermoregulatory hypothalamic region during cold exposure. Normal cold-induced thermogenesis was recovered in Oxtr(-/-) mice by restoring OXTR to the hypothalamus with an adeno-associated virus-Oxtr vector. In addition, brown adipose tissue (BAT) in Oxtr(-/-) mice contained larger lipid droplets in both 10- and 20-week-old compared with BAT from age-matched Oxtr(+/+) control mice. In BAT, the expression level of β3-adrenergic receptor at normal temperature was lower in Oxtr(-/-) mice than that in control mice. In contrast, α2A-adrenergic receptor expression level was higher in BAT from Oxtr(-/-) mice in both normal and cold temperatures. Because β3- and α2A-adrenergic receptors are known to have opposite effects on the thermoregulation, the imbalance of adrenergic receptors is suspected to affect this dysfunction in the thermoregulation. Our study is the first to demonstrate that the central OXT/OXTR system plays important roles in the regulation of body temperature homeostasis.
authors.affiliation: PhD, Laboratory of Molecular Biology, Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai, Miyagi 981-8555, Japan. knishimori@m.tohoku.ac.jp.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kasahara
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sato
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takayanagi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mizukami
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
authors.forename: Shizu
authors.initials: S
authors.lastname: Hidema
authors.forename: Kyoung-Ha
authors.initials: KH
authors.lastname: So
authors.forename: Teruo
authors.initials: T
authors.lastname: Kawada
authors.forename: Nao
authors.initials: N
authors.lastname: Inoue
authors.forename: Ikuo
authors.initials: I
authors.lastname: Ikeda
authors.forename: Sang-Gun
authors.initials: SG
authors.lastname: Roh
authors.forename: Keiichi
authors.initials: K
authors.lastname: Itoi
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Nishimori
mesh_terms: D002001:Adipose Tissue, Brown; D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology*; D003080:Cold Temperature; D004734:Energy Metabolism; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010121:Oxytocin / Q000235:genetics / Q000378:metabolism; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism*
chemical_list: C576074:OXTR protein, mouse; D018045:Receptors, Oxytocin; D010121:Oxytocin