Department of Lifestyle Medicine, Biomedical Engineering Center, Tohoku University Hospital, Aoba-ku, Sendai, Japan.
Int J Neuropsychopharmacol. 2010 Oct;13(9):1261-7. doi: 10.1017/S1461145710000672. Epub 2010 Jun 29.
Hypothalamic pro-opiomelanocortin (POMC) activity is reportedly essential for satiety signalling downstream of serotonin (5-HT). Here we show that food-restricted wild-type mice, which exhibited decreased hypothalamic POMC expression and increased hypothalamic orexin expression, were responsive to m-chlorophenylpiperazine (m-CPP), a 5-HT(2C/1B) receptor agonist, leading to anorexia, whereas food-restricted A(y) mice with decreased hypothalamic POMC and orexin expression, were not. Injection of POMC small interfering RNA (siRNA) oligonucleotide+orexin siRNA oligonucleotide into the third cerebral ventricle was unresponsive to mCPP-induced anorexia, whereas a single injection of POMC or orexin siRNA oligonucleotides elicited a response. The injection of POMC siRNA oligonucleotides suppressed the anorexic effects of sibutramine, a serotonin and noradrenaline re-uptake inhibitor. The injection of orexin siRNA oligonucleotides suppressed the hyperphagia induced by the injection of POMC siRNA oligonucleotides. These findings suggest that functional hypothalamic POMC and orexin activity has a critical role in satiety signalling of mCPP in mice.
据报道，下丘脑的 pro-opiomelanocortin（POMC）活性对于 5-羟色胺（5-HT）下游的饱腹感信号传导至关重要。在这里，我们展示了食物限制的野生型小鼠，其表现出下丘脑 POMC 表达减少和下丘脑食欲素表达增加，对 5-HT（2C/1B）受体激动剂 m-氯苯基哌嗪（m-CPP）有反应，导致厌食症，而下丘脑 POMC 和食欲素表达减少的 A(y) 食物限制型小鼠则没有。将 POMC 小干扰 RNA（siRNA）寡核苷酸+食欲素 siRNA 寡核苷酸注射到第三脑室内对 mCPP 诱导的厌食症没有反应，而单次注射 POMC 或食欲素 siRNA 寡核苷酸则会产生反应。POMC siRNA 寡核苷酸的注射抑制了 5-HT 和去甲肾上腺素再摄取抑制剂西布曲明的厌食作用。食欲素 siRNA 寡核苷酸的注射抑制了 POMC siRNA 寡核苷酸注射引起的过度进食。这些发现表明，功能性下丘脑 POMC 和食欲素活性在小鼠中对 mCPP 的饱腹感信号传导具有关键作用。
