Division of Hypothalamic Research and Endocrinology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Proc Natl Acad Sci U S A. 2011 Jun 28;108(26):10673-8. doi: 10.1073/pnas.1102364108. Epub 2011 Jun 2.
The transcription factor steroidogenic factor 1 (SF-1) is exclusively expressed in the brain in the ventral medial hypothalamic nucleus (VMH) and is required for the development of this nucleus. However, the physiological importance of transcriptional programs regulated by SF-1 in the VMH is not well defined. To delineate the functional significance of SF-1 itself in the brain, we generated pre- and postnatal VMH-specific SF-1 KO mice. Both models of VMH-specific SF-1 KO were susceptible to high fat diet-induced obesity and displayed impaired thermogenesis after acute exposure to high fat diet. Furthermore, VMH-specific SF-1 KO mice showed significantly decreased LepR expression specifically in the VMH, leading to leptin resistance. Collectively, these results indicate that SF-1 directs transcriptional programs in the hypothalamus relevant to coordinated control of energy homeostasis, especially after excess caloric intake.
转录因子类固醇生成因子 1（SF-1）仅在脑的腹内侧下丘脑核（VMH）中表达，是该核发育所必需的。然而，SF-1 调节的转录程序在 VMH 中的生理重要性尚不清楚。为了阐明 SF-1 本身在大脑中的功能意义，我们生成了 VMH 特异性 SF-1 KO 小鼠的产前和产后模型。这两种 VMH 特异性 SF-1 KO 模型均易患高脂肪饮食诱导的肥胖，并在急性高脂肪饮食暴露后表现出产热受损。此外，VMH 特异性 SF-1 KO 小鼠表现出 VMH 中 LepR 表达明显降低，导致瘦素抵抗。总之，这些结果表明，SF-1 指导下丘脑相关的转录程序，以协调能量稳态的控制，尤其是在摄入过多卡路里后。
