Steroidogenic Factor 1 in the Ventromedial Nucleus of the Hypothalamus Regulates Age-Dependent Obesity.
Steroidogenic Factor 1 in the Ventromedial Nucleus of the Hypothalamus Regulates Age-Dependent Obesity.
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DOI：
10.1371/journal.pone.0162352
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Kim KW
中科院分区：
文献类型：
--
作者：
Kinyua AW;Yang DJ;Chang I;Kim KW
下丘脑腹内侧核（VMH）对于调节全身能量平衡是重要的，并且据报道VMH中的病变会导致大量体重增加。核受体类固醇生成因子1（SF-1）是一种已知的VMH标志物，因为它只在大脑的VMH区域表达。SF-1不仅在VMH的发生发展中起重要作用，而且在VMH的生理功能中也起重要作用。在这项研究中，我们产生了产前VMH特异性SF-1基因敲除小鼠，并研究了SF-1的年龄依赖性能量稳态调节。VMH中SF-1的缺失导致胰岛素和瘦素稳态失调和迟发性肥胖，这是由于在正常食物和高脂肪饮食条件下食物摄入增加所致。此外，SF-1消融伴随着能量消耗和体力活动的显著减少，这种效果在老年小鼠中显著。综上所述，我们的数据表明，SF-1是VMH介导的能量稳态调节的关键组分，并暗示SF-1对包括衰老和高脂饮食在内的代谢应激源起保护作用。
The ventromedial nucleus of the hypothalamus (VMH) is important for the regulation of whole body energy homeostasis and lesions in the VMH are reported to result in massive weight gain. The nuclear receptor steroidogenic factor 1 (SF-1) is a known VMH marker as it is exclusively expressed in the VMH region of the brain. SF-1 plays a critical role not only in the development of VMH but also in its physiological functions. In this study, we generated prenatal VMH-specific SF-1 KO mice and investigated age-dependent energy homeostasis regulation by SF-1. Deletion of SF-1 in the VMH resulted in dysregulated insulin and leptin homeostasis and late onset obesity due to increased food intake under normal chow and high fat diet conditions. In addition, SF-1 ablation was accompanied by a marked reduction in energy expenditure and physical activity and this effect was significantly pronounced in the aged mice. Taken together, our data indicates that SF-1 is a key component in the VMH-mediated regulation of energy homeostasis and implies that SF-1 plays a protective role against metabolic stressors including aging and high fat diet.
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