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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-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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

Chan Chi Bun CB   Tse Margaret Chui Ling MC   Liu Xia X   Zhang Shuai S   Schmidt Robin R   Otten Reed R   Liu Liegang L   Ye Keqiang K  

Chemistry & biology 20150305 3


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 express  ...[more]

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