Estradiol stimulates apolipoprotein A-IV gene expression in the nucleus of the solitary tract through estrogen receptor-α

Ling Shen, Yin Liu, David Q.H. Wang, Patrick Tso, Stephen C. Woods, Min Liu

Research output: Contribution to journalArticle

5 Scopus citations


Although estrogens have been implicated in the regulation of apolipoprotein A-IV (apo A-IV) gene expression in the nucleus tractus solitarius, previous studies have not defined the molecular mechanism. The aim of this study was to examine the transcriptional mechanisms involved in regulation of apo A-IV gene expression. Using cultured primary neuronal cells from rat embryonic brainstems, we found that treatment with 10nM 17β-estradiol-3-benzoate (E2) or 4,4',4''-(4-propyl-[1H]-pyrazole- 1,3,5-triyl) trisphenol (an estrogen receptor [ER]α agonist), but not 2,3-bis(4-hydroxyphenyl)- propionitrile (an ERα agonist), significantly increased apo A-IV gene expression, compared with vehicle treatment. This effect of E2 was abolished when the cells were incubated with E2 linked to BSA, which prevents E2 from entering cells, implying that a nongenomic mechanism of E2 is not involved. Two putative estrogen response elements were identified at the 5'-upstream region of the apo A-IV gene promoter, but only 1 of them was able to recruit ERα, leading to increased apo A-IV gene expression, as determined by chromatin immunoprecipitation assay and luciferase activity analysis. A cyclic regimen of E2 or 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol treatment for 8 cycles (4 d/cycle, mimicking the ovarian cycle of female rats) in ovariectomized female rats significantly reduced food intake and body weight gain and increased apo A-IV gene expression in the nucleus tractus solitarius, relative to vehicle. These data collectively demonstrate that nuclear ERα is the primary mediator of E2's action on apo A-IV gene expression and suggest that increased signaling of endogenous apo A-IV may at least partially mediate E2-induced inhibitory effect on feeding. Copyright

Original languageEnglish (US)
Pages (from-to)3882-3890
Number of pages9
Issue number10
Publication statusPublished - Oct 1 2014
Externally publishedYes


ASJC Scopus subject areas

  • Endocrinology

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