{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T23:43:42Z","timestamp":1768002222305,"version":"3.49.0"},"reference-count":41,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,12]],"date-time":"2020-12-12T00:00:00Z","timestamp":1607731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIDDK119135, NIDDK 92779 and NIDDK 95440"],"award-info":[{"award-number":["NIDDK119135, NIDDK 92779 and NIDDK 95440"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Estradiol (E2) enhances the anorectic action of apolipoprotein A-IV (apoA-IV), however, the intracellular mechanisms are largely unclear. Here we reported that the phosphatidylinositol 3-kinase (PI3K)\/Akt signaling pathway was significantly activated by E2 and apoA-IV, respectively, in primary neuronal cells isolated from rat embryonic brainstem. Importantly, the combination of E2 and apoA-IV at their subthreshold doses synergistically activated the PI3K\/Akt signaling pathway. These effects, however, were significantly diminished by the pretreatment with LY294002, a selective PI3K inhibitor. E2-induced activation of the PI3K\/Akt pathway was through membrane-associated ER\u03b1, because the phosphorylation of Akt was significantly increased by PPT, an ER\u03b1 agonist, and by E2-BSA (E2 conjugated to bovine serum albumin) which activates estrogen receptor on the membrane. Centrally administered apoA-IV at a low dose (0.5 \u00b5g) significantly suppressed food intake and increased the phosphorylation of Akt in the nucleus tractus solitarius (NTS) of ovariectomized (OVX) rats treated with E2, but not in OVX rats treated with vehicle. These effects were blunted by pretreatment with LY294002. These results indicate that E2\u2019s regulatory role in apoA-IV\u2019s anorectic action is through the ER\u03b1-PI3K pathway in the NTS. Manipulation of the PI3K\/Akt signaling activation in the NTS may provide a novel therapeutic approach for the prevention and the treatment of obesity-related disorders in females.<\/jats:p>","DOI":"10.3390\/genes11121494","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T00:45:36Z","timestamp":1607906736000},"page":"1494","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Estradiol Enhances Anorectic Effect of Apolipoprotein A-IV through ER\u03b1-PI3K Pathway in the Nucleus Tractus Solitarius"],"prefix":"10.3390","volume":"11","author":[{"given":"Min","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meifeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5439-7651","authenticated-orcid":false,"given":"David Q.-H.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine and Genetics, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Tso","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1006\/appe.2000.0362","article-title":"Estradiol and appetite","volume":"35","author":"Geary","year":"2000","journal-title":"Appetite"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1210\/en.2007-0340","article-title":"Hindbrain administration of estradiol inhibits feeding and activates estrogen receptor-\u03b1-expressing cells in the nucleus tractus solitarius of ovariectomized rats","volume":"149","author":"Thammacharoen","year":"2008","journal-title":"Endocrinology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3163","DOI":"10.1210\/en.2010-0203","article-title":"Estradiol increases the anorectic effect of central apolipoprotein A-IV","volume":"151","author":"Shen","year":"2010","journal-title":"Endocrinology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1002\/cne.21584","article-title":"PI3K signaling effects in hypothalamic neurons mediated by estrogen","volume":"506","author":"Malyala","year":"2008","journal-title":"J.Comp. 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