BDNF/TrkB signaling mediates the anorectic action of estradiol in the nucleus tractus solitarius

Ling Shen, David Q.H. Wang, Meifeng Xu, Stephen C. Woods, Min Liu

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Although compelling evidence indicates that estradiol (E2) acts in the nucleus tractus solitarius (NTS) to reduce food intake, the underlying mechanisms are largely unknown. We now report that estrogen's anorectic action occurs through enhancing the strength of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase (TrkB) signaling in the NTS. Intra-4th-ventricular administration of a low dose of BDNF reduced food intake to a greater extent in ovariectomized (OVX) rats cyclically treated with E2 than in vehicle-treated OVX rats, implying that cyclic E2 replacement increases BDNF's satiating potency. OVX significantly decreased bdnf gene expression in the NTS, and this was reversed by cyclic replacement of E2. Treatment of cultured primary neuronal cells from embryonic rat brainstem with E2 or PPT (ERα agonist), but not with DPN (ERβ agonist), significantly increased bdnf mRNA levels, indicating that ERα is the primary receptor mediating E2's stimulatory effect on bdnf gene expression. Administration of the selective TrkB antagonist, ANA-12, directly into the NTS significantly attenuated E2-induced reductions of food intake and body weight gain in OVX rats, indicating that TrkB receptor activation is necessary for E2's anorectic effect. Finally, relative to controls, OVX mice with bdnf gene knockdown specifically in the NTS had a blunted feeding response to E2. These data collectively imply that BDNF/TrkB receptor signaling in the NTS is a downstream mediator of E2 in the control of energy intake.

Original languageEnglish (US)
Pages (from-to)84028-84038
Number of pages11
JournalOncotarget
Volume8
Issue number48
DOIs
StatePublished - 2017

Keywords

  • BDNF
  • Estrogen
  • Food intake
  • Obesity
  • TrkB receptor

ASJC Scopus subject areas

  • Oncology

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