BDNF/TrkB signaling mediates the anorectic action of estradiol in the nucleus tractus solitarius
Year: 2017
Type: article
Abstract: // Ling Shen 1 , David Q.H. Wang 3 , Meifeng Xu 1 , Stephen C. Woods 2 and Min Liu 1 1 Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA 2 Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA 3 Department of Medicine, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA Correspondence to: Min Liu, email: [email protected] Keywords: BDNF, TrkB receptor, estrogen, food intake, obesity Received: July 18, 2017 Accepted: August 31, 2017 Published: September 19, 2017 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.
Source: Oncotarget
Authors: Ling Shen, David Q.H. Wang, Meifeng Xu, Stephen C. Woods, Min Liu
Institutions: University of Cincinnati, Albert Einstein College of Medicine
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: diamond
Awards: G1800084645, G4556144596, Smarter exosomes derived from engineered MSCs promote neo-vascularization, GPR30 and Hepatic Cholesterol Homeostasis, G6735911969, Ginsenocide Rb1: A Novel Anti-Obesity and Anti-Hyperglycemic Compound, INSULIN AND CNS CONTROL OF BODY WEIGHT AND FOOD INTAKE, G782403223
OpenAlex ID: W2754670538