TY - JOUR
T1 - Steroidogenic factor 1 directs programs regulating diet-induced thermogenesis and leptin action in the ventral medial hypothalamic nucleus
AU - Kim, Ki Woo
AU - Zhao, Liping
AU - Donato, Jose
AU - Kohno, Daisuke
AU - Xu, Yong
AU - Eliasa, Carol F.
AU - Lee, Charlotte
AU - Parker, Keith L.
AU - Elmquist, Joel K.
PY - 2011/6/28
Y1 - 2011/6/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79960617185&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79960617185&partnerID=8YFLogxK
U2 - 10.1073/pnas.1102364108
DO - 10.1073/pnas.1102364108
M3 - Article
C2 - 21636788
AN - SCOPUS:79960617185
VL - 108
SP - 10673
EP - 10678
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 26
ER -
