Knockout mice lacking steroidogenic factor 1 are a novel genetic model of hypothalamic obesity.
Knockout mice lacking steroidogenic factor 1 are a novel genetic model of hypothalamic obesity.
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DOI：
10.1210/endo.143.2.8652
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发表时间：
2002-02
期刊：
影响因子：
4.8
通讯作者：
G. Majdič;M. Young;E. Gomez-Sanchez;P. Anderson;L. Szczepaniak;R. Dobbins;J. McGarry;K. Parker
中科院分区：
文献类型：
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作者：
G. Majdič;M. Young;E. Gomez-Sanchez;P. Anderson;L. Szczepaniak;R. Dobbins;J. McGarry;K. Parker
缺乏类固醇生成因子1（SF-1）的基因敲除（KO）小鼠表现出包括肾上腺和性腺发育不全、促性腺激素表达受损和下丘脑腹内侧核（VMH）异常的表型。对下丘脑腹内侧损伤的啮齿动物的研究表明VMH参与体重调节，表明SF-1 KO小鼠可能提供肥胖的遗传模型。为了防止死亡，用皮质类固醇注射拯救SF-1 KO小鼠，然后从野生型（WT）同窝仔中进行同基因肾上腺移植。WT和SF-1 KO小鼠的皮质酮和ACTH水平无法区分，证明下丘脑-垂体-肾上腺功能恢复。虽然早期的体重与WT同窝小鼠没有显著差异，但SF-1 KO小鼠在8周龄时显著更重，最终体重几乎是WT对照的两倍。SF-1 KO小鼠的肥胖主要是由于活动减少而不是食物摄入增加。瘦素显著增加，胰岛素适度升高，葡萄糖与WT小鼠无法区分。尽管啮齿类动物的性类固醇影响体重，但卵巢切除术并不能消除WT和SF-1 KO小鼠之间的体重差异。这些SF-1基因敲除小鼠是迟发性肥胖的遗传模型，可能有助于阐明VMH在体重调节中的作用。
Knockout (KO) mice lacking steroidogenic factor 1 (SF-1) exhibit a phenotype that includes adrenal and gonadal agenesis, impaired gonadotropin expression, and abnormalities of the ventromedial hypothalamic nucleus (VMH). Studies in rodents with lesions of the ventromedial hypothalamus have implicated the VMH in body weight regulation, suggesting that SF-1 KO mice may provide a genetic model of obesity. To prevent death, SF-1 KO mice were rescued with corticosteroid injections, followed by syngeneic adrenal transplants from wild-type (WT) littermates. Corticosterone and ACTH levels in WT and SF-1 KO mice were indistinguishable, documenting restoration of hypothalamic-pituitary-adrenal function. Although weights at earlier ages did not differ significantly from WT littermates, SF-1 KO mice were significantly heavier by 8 wk of age and eventually weighed almost twice as much as WT controls. Obesity in SF-1 KO mice predominantly resulted from decreased activity rather than increased food intake. Leptin was increased markedly, insulin was modestly elevated, and glucose was indistinguishable from WT mice. Although sex steroids in rodents affect weight, ovariectomy did not abolish the weight difference between WT and SF-1 KO mice. These SF-1 KO mice are a genetic model of late-onset obesity that may help elucidate the role of the VMH in weight regulation.