Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 26, Pages 10673-10678Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1102364108
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Funding
- Mouse Metabolic Phenotyping Core at University of Texas Southwestern Medical Center at Dallas [PL1 DK081182, L1RR024923]
- National Institutes of Health [R01DK53301, R01DK088423, RL1DK081185, K99DK085330, R00DK085330, P30DK079638-03, HD061539]
- American Diabetes Association
- American Heart Association [11POST4880067]
- Canadian Institutes of Health Research
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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.
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