title: SF-1 expression in the hypothalamus is required for beneficial metabolic effects of exercise.
abstract: Exercise has numerous beneficial metabolic effects. The central nervous system (CNS) is critical for regulating energy balance and coordinating whole body metabolism. However, a role for the CNS in the regulation of metabolism in the context of the exercise remains less clear. Here, using genetically engineered mice we assessed the requirement of steroidogenic factor-1 (SF-1) expression in neurons of the ventromedial hypothalamic nucleus (VMH) in mediating the beneficial effects of exercise on metabolism. We found that VMH-specific deletion of SF-1 blunts (a) the reductions in fat mass, (b) improvements in glycemia, and (c) increases in energy expenditure that are associated with exercise training. Unexpectedly, we found that SF-1 deletion in the VMH attenuates metabolic responses of skeletal muscle to exercise, including induction of PGC-1α expression. Collectively, this evidence suggests that SF-1 expression in VMH neurons is required for the beneficial effects of exercise on metabolism.
authors.affiliation: Department of Internal Medicine, Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Teppei
authors.initials: T
authors.lastname: Fujikawa
authors.affiliation: Department of Internal Medicine, Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Castorena
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Mackenzie
authors.initials: M
authors.lastname: Pearson
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Kusminski
authors.affiliation: Department of Internal Medicine, Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Newaz
authors.initials: N
authors.lastname: Ahmed
authors.affiliation: Department of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Pavan K
authors.initials: PK
authors.lastname: Battiprolu
authors.affiliation: Department of Pharmacology, Wonju College of Medicine, Yonsei University, Wonju, South Korea.|Department of Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju, South Korea.|Institute of Lifestyle Medicine and Nuclear Receptor Research Consortium, Wonju College of Medicine, Yonsei University, Wonju, South Korea.
authors.forename: Ki Woo
authors.initials: KW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Syann
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, United States.|Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Hill
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States.|Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Scherer
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: William L
authors.initials: WL
authors.lastname: Holland
authors.affiliation: Department of Internal Medicine, Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, United States.|Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States.
authors.forename: Joel K
authors.identifier: 0000-0001-6929-6370
authors.initials: JK
authors.lastname: Elmquist
mesh_terms: D000818:Animals; D004734:Energy Metabolism; D015870:Gene Expression; D051379:Mice; D010805:Physical Conditioning, Animal; D054339:Steroidogenic Factor 1 / Q000096:biosynthesis*; D014697:Ventromedial Hypothalamic Nucleus / Q000502:physiology*
chemical_list: D054339:Steroidogenic Factor 1; C515058:steroidogenic factor 1, mouse
keywords: Nr5a1; SF-1; VMH; exercise; hypothalamus; metabolism; mouse; neuroscience