Thermoneutral conditions correct the obese phenotype in female, but not male, Kiss1r knockout mice
Thermoneutral conditions correct the obese phenotype in female, but not male, Kiss1r knockout mice
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DOI：
10.1016/j.jtherbio.2020.102592
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发表时间：
2020-05-01
影响因子：
2.7
通讯作者：
Smith, J. T.
中科院分区：
文献类型：
--
作者：
Halvorson, C. L.;De Bond, J. P.;Smith, J. T.
Kisspeptin 是一种激活促性腺激素释放激素 (GnRH) 神经元的神经肽，也被认为是能量平衡的调节剂。与野生型 (WT) 对照相比，Kisspeptin 受体 (Kiss1r) 敲除 (KO) 小鼠在成年后表现出肥胖表型，因为能量消耗减少。此外，实验证据表明，典型啮齿动物饲养条件的温度（22 摄氏度）会使小鼠的新陈代谢高于基础水平。雌性 Kiss1r KO 小鼠表现出核心温度降低和对急性寒冷挑战的温度适应受损，这表明它们的温度稳态过程发生了改变。本研究检查了去性腺切除的 Kiss1r KO 小鼠在亚热中性和热中性温度（22 摄氏度和 30 摄氏度）下的表型。我们的结果证实了 Kiss1r KO 小鼠在 22 摄氏度下的肥胖表型，并揭示了热中性对表型的性别二态性影响。在雌性 KO 小鼠中，22℃时观察到的肥胖在 30℃ 时减弱。22℃时 KO 雌性小鼠的血浆瘦素水平高于 WT 雌性小鼠 (P < 0.001)，但 30℃ 时则不然。重要的是，22℃时，与 WT 小鼠相比，KO 小鼠棕色脂肪组织中 Ucp1 mRNA 的表达较低 (P < 0.05)，但与 WT 小鼠没有差异。 WT 在 30 摄氏度。在雄性 KO 小鼠中，在 22 摄氏度和 30 摄氏度下观察到代谢表型。这些结果为 Kisspeptin 通过改变能量消耗介导的肥胖调节提供了进一步的证据。此外，与 WT 相比，热中性外壳减轻了雌性 Kiss1r KO 小鼠的肥胖表型，表明这些小鼠的损伤可能与无法适应 22 摄氏度下经历的慢性冷应激有关。
Kisspeptin, a neuropeptide that activates gonadotropin-releasing hormone (GnRH) neurons, has also been implicated as a regulator of energy balance. Kisspeptin receptor (Kiss1r) knockout (KO) mice display an obese phenotype in adulthood compared to wild-type (WT) controls due to reduced energy expenditure. Additionally, experimental evidence shows that the temperature of typical rodent housing conditions (22 degrees C) increases the metabolism of mice above basal levels. Female Kiss1r KO mice show reduced core temperature and impaired temperature adaptation to an acute cold challenge, suggesting their temperature homeostasis processes are altered. The present study examined the phenotype of gonadectomised Kiss1r KO mice at both sub-thermoneutral and thermoneutral temperature (22 degrees C and 30 degrees C). Our results confirmed the obese phenotype in Kiss1r KO mice at 22 degrees C, and revealed a sexually dimorphic effect of thermal neutrality on the phenotype. In female KO mice, the obesity observed at 22 degrees C was attenuated at 30 degrees C. Plasma leptin levels were higher in KO than WT female mice at 22 degrees C (P < 0.001) but not at 30 degrees C. Importantly, the expression of Ucp1 mRNA in brown adipose tissue was lower in KO mice compared to WT mice at 22 degrees C (P < 0.05), but not different from WT at 30 degrees C. In male KO mice, a metabolic phenotype was observed at 22 degrees C and 30 degrees C. These results provide further evidence for kisspeptin-mediated regulation of adiposity via altered energy expenditure. Moreover, thermoneutral housing alleviated the obese phenotype in female Kiss1r KO mice, compared to WT, indicating the impairment in these mice may relate to an inability to adapt to the chronic cold stress that is experienced at 22 degrees C.