title: Apolipoprotein E reduces food intake via PI3K/Akt signaling pathway in the hypothalamus.
abstract: Apolipoprotein E (apoE) is a satiation factor. While central apoE administration reduces food intake, the specific intracellular signaling mechanisms activated by apoE remain largely unknown. Using primary cultured hypothalamic neurons, we demonstrated that apoE treatment (50 nM) elicited rapid activation of the phosphatidylinositol-3-kinase (PI3K)/Akt signaling cascade. Specifically, apoE induced the phosphorylation of Akt, peaking at 30 min, and the increased phosphorylation of Akt was significantly attenuated after pretreatment with LY294002 (50 μM), an inhibitor of the PI3K signaling pathway. To determine whether the activation of PI3K by apoE is required for the ability of apoE to reduce food intake, LY294002 (1 nmol) was infused into the 3rd-cerebral ventricle before injection of an anorectic dose of apoE. Consistent with our previous report, apoE (4 μg) exerted significant reduction of food intake in the 4-h fasted rats, compared with saline. Pretreatment with LY294002 significantly attenuated the potency of exogenous apoE to induce satiation, while the same dose of PI3K inhibitor by itself caused only a slight non-significant decrease of food intake. These results indicate that the activation of the PI3K/Akt pathway is necessary for the acute effects of apoE on food intake.
authors.affiliation: Cincinnati Obesity Research Center, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
authors.forename: Ling
authors.initials: L
authors.lastname: Shen
authors.forename: David Q-H
authors.initials: DQ
authors.lastname: Wang
authors.forename: Patrick
authors.initials: P
authors.lastname: Tso
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Jandacek
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Woods
authors.forename: Min
authors.initials: M
authors.lastname: Liu
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000494:pharmacology*; D002478:Cells, Cultured; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D001057:Apolipoproteins E; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt