Activation of muscular TrkB by its small molecular agonist 7,8-dihydroxyflavone sex-dependently regulates energy metabolism in diet-induced obese mice.

ABSTRACT: Chronic activation of brain-derived neurotrophic factor (BDNF) receptor TrkB is a potential method to prevent development of obesity, but the short half-life and nonbioavailable nature of BDNF hampers validation of the hypothesis. We report here that activation of muscular TrkB by the BDNF mimetic, 7,8-dihydroxyflavone (7,8-DHF), is sufficient to protect the development of diet-induced obesity in female mice. Using in vitro and in vivo models, we found that 7,8-DHF treatment enhanced the expression of uncoupling protein 1 (UCP1) and AMP-activated protein kinase (AMPK) activity in skeletal muscle, which resulted in increased systemic energy expenditure, reduced adiposity, and improved insulin sensitivity in female mice fed a high-fat diet. This antiobesity activity of 7,8-DHF is muscular Tr

SUBMITTER: Chan CB 

PROVIDER: S-EPMC4369457 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature