Estradiol enhances anorectic effect of apolipoprotein A-IV through Erα-PI3K pathway in the nucleus tractus solitarius

Min Liu, Ling Shen, Meifeng Xu, David Q.H. Wang, Patrick Tso

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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 ERα, because the phosphorylation of Akt was significantly increased by PPT, an ERα 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 µg) 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’s regulatory role in apoA-IV’s anorectic action is through the ERα-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.

Original languageEnglish (US)
Article number1494
Pages (from-to)1-12
Number of pages12
JournalGenes
Volume11
Issue number12
DOIs
StatePublished - Dec 2020

Keywords

  • Apolipoprotein A-IV
  • Estradiol
  • Food intake
  • Nucleus tractus solitarius
  • PI3K/Akt signaling

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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