Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain.
Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain.
J Neuroendocrinol. 2024 Oct;36(10):e13433. doi: 10.1111/jne.13433. Epub 2024 Jul 23.
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.
kisspeptins 是生殖轴的重要调节因子，具有强烈激活促性腺激素释放激素神经元的能力，同时也是代谢调节生育能力的中枢途径。最近的证据表明， kisspeptins 本身也可能调节多种代谢参数，包括体重、食物摄入或能量消耗，但它们的实际作用和作用部位尚不清楚。我们在此介绍了一系列研究，这些研究探讨了 kisspeptin-10（Kp-10；每天分别给予 1 nmol 和 3 nmol）中枢和外周给药 11 天对雌雄小鼠的代谢影响。为了评估 Kp-10 的直接代谢作用与它调节性腺激素分泌的间接作用，我们在去势并分别用固定的生理剂量睾酮或 17β-雌二醇补充的成年雄性和雌性小鼠中测试了 kisspeptin 的作用。Kp-10 的中枢给药减少了雄性小鼠的食物摄入，尤其是在黑暗期（50%），同时总能量消耗和夜间能量消耗（16%）和运动活动（~70%）减少。相比之下，在雌性小鼠中检测到相反的模式，总能量消耗和夜间运动活动增加（>65%），尽管食物摄入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，雌雄小鼠均未检测到体重差异。外周给予 Kp-10 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 小时食物摄入略有增加，这表明 kisspeptins 在控制能量代谢中主要发挥中枢作用。最后，Kp-10 的中枢或外周治疗对葡萄糖耐量和胰岛素敏感性没有显著影响。总之，我们的数据揭示了 kisspeptins 在控制关键代谢参数中的潜在作用，包括食物摄入、能量消耗和运动活动，其作用优先发生在中枢水平，且与性激素无关，但存在性别二态性。
