TY - JOUR
T1 - Oxytocin receptor in the hypothalamus is sufficient to rescue normal thermoregulatory function in male oxytocin receptor knockout mice
AU - Kasahara, Yoshiyuki
AU - Sato, Keisuke
AU - Takayanagi, Yuki
AU - Mizukami, Hiroaki
AU - Ozawa, Keiya
AU - Hidema, Shizu
AU - So, Kyoung Ha
AU - Kawada, Teruo
AU - Inoue, Nao
AU - Ikeda, Ikuo
AU - Roh, Sang Gun
AU - Itoi, Keiichi
AU - Nishimori, Katsuhiko
PY - 2013/11/1
Y1 - 2013/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84886512847&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84886512847&partnerID=8YFLogxK
U2 - 10.1210/en.2012-2206
DO - 10.1210/en.2012-2206
M3 - Article
C2 - 24002032
AN - SCOPUS:84886512847
VL - 154
SP - 4305
EP - 4315
JO - Endocrinology
JF - Endocrinology
SN - 0013-7227
IS - 11
ER -