Abstract：
Kisspeptins are essential regulators of the reproductive axis, with capacity to potently activate gonadotropin-releasing hormone neurons, acting also as central conduits for the metabolic regulation of fertility. Recent evidence suggests that kisspeptins per se may also modulate several metabolic parameters, including body weight, food intake or energy expenditure, but their actual roles and site(s) of action remain unclear. We present herein a series of studies addressing the metabolic effects of central and peripheral administration of kisspeptin-10 (Kp-10; 1 nmol and 3 nmol daily, respectively) for 11 days in mice of both sexes. To assess direct metabolic actions of Kp-10 versus those derived indirectly from its capacity to modulate gonadal hormone secretion, kisspeptin effects were tested in adult male and female mice gonadectomized and supplemented with fixed, physiological doses of testosterone or 17β-estradiol, respectively. Central administration of Kp-10 decreased food intake in male mice, especially during the dark phase (~50%), which was accompanied by a reduction in total and nocturnal energy expenditure (~16%) and locomotor activity (~70%). In contrast, opposite patterns were detected in female mice, with an increase in total and nocturnal locomotor activity (>65%), despite no changes in food intake or energy expenditure. These changes were independent of body weight, as no differences were detected in mice of both sexes at the end of Kp-10 treatments. Peripheral administration of Kp-10 failed to alter any of the metabolic parameters analyzed, except for a decrease in locomotor activity in male mice and a subtle increase in 24 h food intake in female mice, denoting a predominant central role of kisspeptins in the control of energy metabolism. Finally, glucose tolerance and insulin sensitivity were not significantly affected by central or peripheral treatment with Kp-10. In conclusion, our data reveal a potential role of kisspeptins in the control of key metabolic parameters, including food intake, energy expenditure and locomotor activity, with a preferential action at central level, which is sex steroid-independent but sexually dimorphic.
摘要：
Kisspeptins是生殖轴的重要调节剂，具有强力激活促性腺激素释放激素神经元的能力，也作为生育代谢调节的中心管道。最近的证据表明，kisspeptins本身也可能调节几种代谢参数，包括体重,食物摄入或能量消耗，但他们的实际角色和行动地点仍不清楚。我们在此提出了一系列研究，以解决中枢和外周给药kisspeptin-10（Kp-10;每天1nmol和3nmol，分别）在两种性别的小鼠中持续11天。为了评估Kp-10的直接代谢作用与间接来自其调节性腺激素分泌能力的代谢作用，在成年雄性和雌性小鼠中测试了kisspeptin的作用，睾酮或17β-雌二醇的生理剂量，分别。Kp-10的中央管理减少了雄性小鼠的食物摄入，特别是在黑暗阶段（〜50％），伴随着总能量消耗和夜间能量消耗（〜16％）和运动活动（〜70％）的减少。相比之下,在雌性小鼠中检测到相反的模式，随着总运动活动和夜间运动活动的增加(>65%)，尽管食物摄入量或能量消耗没有变化。这些变化与体重无关，因为在Kp-10治疗结束时，在两种性别的小鼠中均未检测到差异。Kp-10的外周给药未能改变分析的任何代谢参数，除了雄性小鼠的运动活动减少和雌性小鼠的24小时食物摄入量的细微增加，表示kisspeptins在控制能量代谢中的主要核心作用。最后,Kp-10的中枢或外周治疗对糖耐量和胰岛素敏感性没有显着影响。总之,我们的数据揭示了kisspeptins在关键代谢参数控制中的潜在作用，包括食物摄入，能量消耗和运动活动，在中央一级采取优先行动，与性类固醇无关，但性二态。
