促性腺激素抑制激素(GnIH)自发现以来在脊椎动物的繁殖中起着至关重要的作用。最近,GnIH在食欲和能量代谢中的调节作用已经出现,尽管其精确的生理机制仍然未知。因此,本研究评估了单一或长期GnIH治疗(通过腹膜内注射给药)对食物摄入的影响,鸡的体重和糖脂代谢,同时研究了GnIH诱导的肥胖和糖脂代谢紊乱的可能的神经内分泌因素及其机制。我们的结果表明,对鸡腹腔内施用GnIH导致体重明显增加,高脂血症,高血糖和葡萄糖耐受不良。随后,代谢组学和药理抑制5-HT2C受体的研究结果表明,阻断5-HT2C受体增强了GnIH对食物摄入的影响,体重和血糖和血脂水平,导致GnIH诱导的高血糖,高脂血症和肝脏脂质沉积甚至更糟,提示通过5-HT2C受体的外周5-HT可能充当负反馈调节剂,与GnIH相互作用,并共同稳态控制鸡的能量平衡。我们目前的研究提供了GnIH和5-HT在体内药理学水平的食物摄入和能量代谢之间的串扰的证据,并提出了这些相互作用的分子基础。提示GnIH与5-HT之间的功能相互作用可能为了解神经内分泌网络参与食欲和能量代谢的机制开辟新的途径,并为预防肥胖提供新的治疗策略。糖尿病和代谢紊乱。
BACKGROUND: Since the discovery of gonadotropin-inhibitory hormone (GnIH), it has been found to play a critical role in reproduction in vertebrates. Recently, a regulatory role of GnIH in appetite and energy metabolism has emerged, although its precise physiological mechanisms remain unknown.
METHODS: Thus, the present study evaluated the effects of a single or long-term intraperitoneal GnIH treatment on the food intake, weight, and glucolipid metabolism of chickens, as well as investigating the possible neuroendocrinology factors and mechanisms involved in GnIH-induced obesity and glucolipid metabolism disorder.
RESULTS: Our results show that the intraperitoneal administration of GnIH to chickens resulted in a marked body mass increase, hyperlipidemia, hyperglycemia, and glucose intolerance. Subsequently, the results of metabolomics studies and the pharmacological inhibition of the 5-HT2C receptor revealed that blocking the 5-HT2C receptor reinforced the effects of GnIH on food intake, body weight, and blood glucose and lipid levels, resulting in even worse cases of GnIH-induced hyperglycemia, hyperlipidemia, and hepatic lipid deposition. This suggests that, via the 5-HT2C receptor, peripheral 5-HT may act as a negative feedback regulator to interplay with GnIH and jointly control energy balance homeostasis in chickens.
CONCLUSIONS: Our present study provides evidence of cross-talk between GnIH and 5-HT in food intake and energy metabolism at the in vivo pharmacological level, and it proposes a molecular basis for these interactions, suggesting that functional interactions between GnIH and 5-HT may open new avenues for understanding the mechanism of the neuroendocrine network involved in appetite and energy metabolism, as well as providing a new therapeutic strategy to prevent obesity, diabetes, and metabolic disorders.