title: Steroidogenic factor 1 directs programs regulating diet-induced thermogenesis and leptin action in the ventral medial hypothalamic nucleus.
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.
authors.affiliation: Division of Hypothalamic Research and Endocrinology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Ki Woo
authors.initials: KW
authors.lastname: Kim
authors.forename: Liping
authors.initials: L
authors.lastname: Zhao
authors.forename: Jose
authors.initials: J
authors.lastname: Donato
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kohno
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.forename: Carol F
authors.initials: CF
authors.lastname: Elias
authors.forename: Charlotte
authors.initials: C
authors.lastname: Lee
authors.forename: Keith L
authors.initials: KL
authors.lastname: Parker
authors.forename: Joel K
authors.initials: JK
authors.lastname: Elmquist
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage*; D002149:Energy Intake; D006706:Homeostasis; D020738:Leptin / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D054339:Steroidogenic Factor 1 / Q000235:genetics / Q000502:physiology*; D022722:Thermogenesis; D014697:Ventromedial Hypothalamic Nucleus / Q000502:physiology*
chemical_list: D004041:Dietary Fats; D020738:Leptin; D054339:Steroidogenic Factor 1; C515058:steroidogenic factor 1, mouse