Unknown

Dataset Information

0

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 TrkB-dependent as 7,8-DHF cannot mitigate diet-induced obesity in female muscle-specific TrkB knockout mice. Hence, our data reveal that chronic activation of muscular TrkB is useful in alleviating obesity and its complications.

SUBMITTER: Chan CB 

PROVIDER: S-EPMC4369457 | BioStudies | 2015-01-01

REPOSITORIES: biostudies

Similar Datasets

2011-01-01 | S-EPMC3770732 | BioStudies
1000-01-01 | S-EPMC4793717 | BioStudies
1000-01-01 | S-EPMC5777001 | BioStudies
2014-01-01 | S-EPMC4240709 | BioStudies
2015-01-01 | S-EPMC4613243 | BioStudies
2015-01-01 | S-EPMC4754355 | BioStudies
2021-01-01 | S-EPMC7920311 | BioStudies
1000-01-01 | S-EPMC2823863 | BioStudies
2018-01-01 | S-EPMC7292275 | BioStudies
2015-01-01 | S-EPMC4433561 | BioStudies