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

Ki Woo Kim, Liping Zhao, Jose Donato, Daisuke Kohno, Yong Xu, Carol F. Eliasa, Charlotte Lee, Keith L. Parker, Joel K. Elmquist

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Abstract

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 preand postnatal VMH-specific SF-1 KO mice. Both models of VMHspecific 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.

Original languageEnglish
Pages (from-to)10673-10678
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number26
DOIs
Publication statusPublished - 2011 Jun 28

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