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

Author
item KIM, KI WOO - University Of Texas Southwestern Medical Center
item ZHAO, LIPING - National Institute Of Biological Science
item DONATO, JR., JOSE - University Of Texas Southwestern Medical Center
item KOHNO, DAISUKE - University Of Texas Southwestern Medical Center
item XU, YONG - Children'S Nutrition Research Center (CNRC)
item ELIAS, CAROL - University Of Texas Southwestern Medical Center
item LEE, CHARLOTTE - University Of Texas Southwestern Medical Center
item PARKER, KEITH - University Of Texas Southwestern Medical Center
item ELMQUIST, JOEL - University Of Texas Southwestern Medical Center

Submitted to: Proceedings of the National Academy of Sciences (PNAS)
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/1/2011
Publication Date: 6/28/2011
Citation: Kim, K., Zhao, L., Donato Jr., J., Kohno, D., Xu, Y., Elias, C.F., Lee, C., Parker, K.L., Elmquist, J.K. 2011. Steroidogenic factor 1 directs programs regulating diet-induced thermogenesis and leptin action in the ventral medial hypothalamic nucleus. Proceedings of the National Academy of Sciences. 108(26):10673-10678.

Interpretive Summary: Certain aspects of the brain control feeding behavior and body weight, but the mechanisms for this regulation are not fully understood. We showed that the loss of a specific gene called SF-1 in the brain caused obesity in mice. These findings suggest that interventions targeting this SF-1 gene in the brain may be used to prevent or treat obesity in humans.

Technical 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 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.