title: PI3K signaling in the ventromedial hypothalamic nucleus is required for normal energy homeostasis.
abstract: Phosphatidyl inositol 3-kinase (PI3K) signaling in the hypothalamus has been implicated in the regulation of energy homeostasis, but the critical brain sites where this intracellular signal integrates various metabolic cues to regulate food intake and energy expenditure are unknown. Here, we show that mice with reduced PI3K activity in the ventromedial hypothalamic nucleus (VMH) are more sensitive to high-fat diet-induced obesity due to reduced energy expenditure. In addition, inhibition of PI3K in the VMH impaired the ability to alter energy expenditure in response to acute high-fat diet feeding and food deprivation. Furthermore, the acute anorexigenic effects induced by exogenous leptin were blunted in the mutant mice. Collectively, our results indicate that PI3K activity in VMH neurons plays a physiologically relevant role in the regulation of energy expenditure.
authors.affiliation: Division of Hypothalamic Research, Departments of Internal Medicine and Pharmacology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.forename: Jennifer W
authors.initials: JW
authors.lastname: Hill
authors.forename: Makoto
authors.initials: M
authors.lastname: Fukuda
authors.forename: Laurent
authors.initials: L
authors.lastname: Gautron
authors.forename: Jong-Woo
authors.initials: JW
authors.lastname: Sohn
authors.forename: Ki-Woo
authors.initials: KW
authors.lastname: Kim
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Lee
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Choi
authors.forename: Danielle A
authors.initials: DA
authors.lastname: Lauzon
authors.forename: Harveen
authors.initials: H
authors.lastname: Dhillon
authors.forename: Bradford B
authors.initials: BB
authors.lastname: Lowell
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Zigman
authors.forename: Jean J
authors.initials: JJ
authors.lastname: Zhao
authors.forename: Joel K
authors.initials: JK
authors.lastname: Elmquist
mesh_terms: D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology; D004041:Dietary Fats / Q000494:pharmacology; D004734:Energy Metabolism; D006706:Homeostasis; D020738:Leptin / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction; D014697:Ventromedial Hypothalamic Nucleus / Q000201:enzymology*
chemical_list: D001067:Appetite Depressants; D004041:Dietary Fats; D020738:Leptin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors