School of Human Sciences, The University of Western Australia, Perth, Western Australia, Australia.
Department of OBGYN and Reproductive Sciences, University of California, San Diego, La Jolla, CA, USA.
Mol Cell Endocrinol. 2022 Feb 15;542:111530. doi: 10.1016/j.mce.2021.111530. Epub 2021 Dec 8.
Kisspeptin is vital for the regulation of both fertility and metabolism. Kisspeptin receptor (Kiss1r) knockout (KO) mice exhibit increased adiposity and reduced energy expenditure in adulthood. Kiss1r mRNA is expressed in brown adipose tissue (BAT) and Kiss1r KO mice exhibit reduced Ucp1 mRNA in BAT and impaired thermogenesis. We hypothesised that mice with diminished kisspeptin signalling would exhibit reduced core body temperature (Tc) and altered dynamics of circadian and ultradian rhythms of Tc. Tc was recorded every 15-min over 14-days in gonadectomised wild-type (WT), Kiss1r KO, and also Kiss1-Cre (95% reduction in Kiss1 transcription) mice. Female Kiss1r KOs had higher adiposity and lower Ucp1 mRNA in BAT than WTs. No change was detected in Kiss1-Cre mice. Mean Tc during the dark phase was lower in female Kiss1r KOs versus WTs, but not Kiss1-Cre mice. Female Kiss1r KOs had a lower mesor and amplitude of the circadian rhythm of Tc than did WTs. In WT mice, there were more episodic ultradian events (EUEs) of Tc during the dark phase than the light phase, but this measure was similar between dark and light phases in Kiss1r KO and Kiss1-Cre mice. The amplitude of EUEs was higher in the dark phase in female Kiss1r KO and male Kiss1-Cre mice. Given the lack of clear metabolic phenotype in Kiss1-Cre mice, 5% of Kiss1 transcription may be sufficient for proper metabolic control, as was shown for fertility. Moreover, the observed alterations in Tc suggest that kisspeptin has a role in circadian and ultradian rhythm-driven pathways.
Kisspeptin 对生殖和代谢的调节都至关重要。 Kisspeptin 受体 (Kiss1r) 敲除 (KO) 小鼠在成年后表现出肥胖增加和能量消耗减少。 Kiss1r mRNA 在棕色脂肪组织 (BAT) 中表达，Kiss1r KO 小鼠的 BAT 中 Ucp1 mRNA 减少，产热受损。我们假设，kisspeptin 信号减弱的小鼠会表现出核心体温 (Tc) 降低，并改变 Tc 的昼夜节律和超昼夜节律的动态。在去势的野生型 (WT)、Kiss1r KO 和 Kiss1-Cre (Kiss1 转录减少 95%) 小鼠中，每 15 分钟记录一次 Tc，持续 14 天。雌性 Kiss1r KO 的脂肪量较高，BAT 中的 Ucp1 mRNA 较低，而 WT 则没有变化。在 Kiss1-Cre 小鼠中未检测到变化。与 WT 相比，雌性 Kiss1r KO 小鼠在黑暗阶段的平均 Tc 较低，但 Kiss1-Cre 小鼠则没有。雌性 Kiss1r KO 小鼠的 Tc 昼夜节律的中值和振幅均低于 WT。在 WT 小鼠中，黑暗阶段的 Tc 超昼夜事件 (EUE) 比亮期多，但 Kiss1r KO 和 Kiss1-Cre 小鼠的暗期和亮期之间这一测量值相似。在雌性 Kiss1r KO 和雄性 Kiss1-Cre 小鼠中，黑暗期 EUE 的振幅更高。鉴于 Kiss1-Cre 小鼠中没有明显的代谢表型，5%的 Kiss1 转录可能足以进行适当的代谢控制，就像生育能力一样。此外，观察到的 Tc 变化表明 kisspeptin 在昼夜节律和超昼夜节律驱动的途径中发挥作用。
