title: Estradiol increases the anorectic effect of central apolipoprotein A-IV.
abstract: Estrogens have potent suppressive effects on food intake and body weight in many species, including humans. Compelling evidence suggests estrogen's anorectic action is through an indirect mechanism by enhancing the strength of other physiological signals that reduce meal size such as apolipoprotein A-IV (apo A-IV), a satiation factor from the gut and brain. We determined whether estradiol, the primary form of estrogen, modulates the anorectic effect of apo A-IV. Intrafourth ventricular administration of low doses of apo A-IV reduced food intake to a greater extent in ovariectomized (OVX) rats cyclically treated with estradiol than in vehicle-treated OVX controls, implying that cyclic estradiol replacement increases the satiating potency of apo A-IV. OVX significantly increased food intake and body weight but decreased apo A-IV gene expression in the nucleus tractus solitarius (NTS). All of these alterations were reversed by cyclic regimen of estradiol treatment. The finding of colocalization of apo A-IV with estrogen receptor-alpha in the NTS suggests that estradiol might act locally in the NTS to up-regulate apo A-IV gene expression. Finally, OVX apo A-IV knockout mice had a smaller feeding response to estradiol because they ate significantly more food and gained more body weight than OVX wild-type controls during the period of cyclic estradiol replacement. These data indicate that an increased signaling of endogenous apo A-IV may partially mediate estradiol-induced inhibitory effect on feeding.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45237-0507, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Shen
authors.forename: David Q-H
authors.initials: DQ
authors.lastname: Wang
authors.forename: Chun-Min
authors.initials: CM
authors.lastname: Lo
authors.forename: Patrick
authors.initials: P
authors.lastname: Tso
authors.forename: W Sean
authors.initials: WS
authors.lastname: Davidson
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Woods
authors.forename: Min
authors.initials: M
authors.lastname: Liu
mesh_terms: D000818:Animals; D001054:Apolipoproteins A / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D004435:Eating / Q000187:drug effects / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D010052:Ovariectomy; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D001054:Apolipoproteins A; D047628:Estrogen Receptor alpha; C022205:apolipoprotein A-IV; D004958:Estradiol