Kisspeptin impacts on circadian and ultradian rhythms of core body temperature: Evidence in kisspeptin receptor knockout and kisspeptin knockdown mice.

Kisspeptin impacts on circadian and ultradian rhythms of core body temperature: Evidence in kisspeptin receptor knockout and kisspeptin knockdown mice.
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DOI:
10.1016/j.mce.2021.111530
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发表时间:
2022-02-15
影响因子:
4.1
通讯作者:
Smith, Jeremy T.
Smith, Jeremy T.
中科院分区:
医学2区
文献类型:
--
作者:
Kavanagh, Georgia S.;Tadi, Jason;Balkenhol, Sydney M.;Kauffman, Alexander S.;Maloney, Shane K.;Smith, Jeremy T.

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Kisspeptin对调节生育和新陈代谢至关重要。Kisspeptin受体(Kiss 1 r)敲除(KO)小鼠在成年期表现出肥胖增加和能量消耗减少。Kiss 1 r mRNA在棕色脂肪组织(BAT)中表达,Kiss 1 r KO小鼠表现出BAT中Ucp 1 mRNA减少和产热受损。我们假设,小鼠与kisspeptin信号减少将表现出降低核心体温(Tc)和改变的昼夜节律和超昼夜节律的Tc。在性腺切除的野生型(WT)、Kiss 1 r KO以及Kiss 1-Cre(Kiss 1转录减少95%)小鼠中,在14天内每15分钟记录一次Tc。雌性Kiss 1 r科斯在BAT中的肥胖率高于WT,而Ucp 1 mRNA水平低于WT。Kiss 1-Cre小鼠未检测到变化。雌性Kiss 1 r科斯小鼠在黑暗期的平均Tc低于WT小鼠,但Kiss 1-Cre小鼠并非如此。女性Kiss 1 r科斯有一个较低的中位数和幅度的昼夜节律的Tc比WT。在野生型小鼠中,有更多的情节超日事件(EUE)的Tc在黑暗阶段比光明阶段,但这一措施是类似的黑暗和光明阶段之间的Kiss 1 r KO和Kiss 1-Cre小鼠。Kiss 1-Cre基因敲除小鼠和Kiss 1-Cre基因敲除小鼠在暗相时EUE的幅度均高于Kiss 1基因敲除小鼠。鉴于Kiss 1-Cre小鼠缺乏明确的代谢表型,5%的Kiss 1转录可能足以进行适当的代谢控制,如生育力所示。此外,观察到的Tc的变化表明,kisspeptin在昼夜节律和超昼夜节律驱动的通路中发挥作用。
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.
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