Phosphatidyl inositol 3-kinase signaling in hypothalamic proopiomelanocortin neurons contributes to the regulation of glucose homeostasis.
Recent studies demonstrated a role for hypothalamic insulin and leptin action in the regulation of glucose homeostasis. This regulation involves proopiomelanocortin (POMC) neurons because suppression of phosphatidyl inositol 3-kinase (PI3K) signaling in these neurons blunts the acute effects of insulin and leptin on POMC neuronal activity. In the current study, we investigated whether disruption of PI3K signaling in POMC neurons alters normal glucose homeostasis using mouse models designed to both increase and decrease PI3K-mediated signaling in these neurons. We found that deleting p85alpha alone induced resistance to diet-induced obesity. In contrast, deletion of the p110alpha catalytic subunit of PI3K led to increased weight gain and adipose tissue along with reduced energy expenditure. Independent of these effects, increased PI3K activity in POMC neurons improved insulin sensitivity, whereas decreased PI3K signaling resulted in impaired glucose regulation. These studies show that activity of the PI3K pathway in POMC neurons is involved in not only normal energy regulation but also glucose homeostasis.
Hill
Jennifer W
JW
Division of Hypothalamic Research, Department of Internal Medicine, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9077, USA.
Xu
Yong
Y
Preitner
Frederic
F
Fukuda
Makota
M
Cho
You-Ree
YR
Luo
Ji
J
Balthasar
Nina
N
Coppari
Roberto
R
Cantley
Lewis C
LC
Kahn
Barbara B
BB
Zhao
Jean J
JJ
Elmquist
Joel K
JK
D000818:Animals; D004734:Energy Metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D011333:Pro-Opiomelanocortin; D019869:Phosphatidylinositol 3-Kinases; D005947:Glucose