PI3K signaling in the ventromedial hypothalamic nucleus is required for normal energy homeostasis.
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.
Xu
Yong
Y
Division of Hypothalamic Research, Departments of Internal Medicine and Pharmacology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Hill
Jennifer W
JW
Fukuda
Makoto
M
Gautron
Laurent
L
Sohn
Jong-Woo
JW
Kim
Ki-Woo
KW
Lee
Charlotte E
CE
Choi
Michelle J
MJ
Lauzon
Danielle A
DA
Dhillon
Harveen
H
Lowell
Bradford B
BB
Zigman
Jeffrey M
JM
Zhao
Jean J
JJ
Elmquist
Joel K
JK
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*
D001067:Appetite Depressants; D004041:Dietary Fats; D020738:Leptin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors