Steroidogenic factor 1 directs programs regulating diet-induced thermogenesis and leptin action in the ventral medial hypothalamic nucleus

KW Kim, L Zhao, J Donato Jr… - Proceedings of the …, 2011 - National Acad Sciences
KW Kim, L Zhao, J Donato Jr, D Kohno, Y Xu, CF Elias, C Lee, KL Parker, JK Elmquist
Proceedings of the National Academy of Sciences, 2011National Acad Sciences
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 …
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.
National Acad Sciences