Activation of Muscular TrkB by its Small Molecular Agonist 7,8-Dihydroxyflavone Sex-Dependently Regulates Energy Metabolism in Diet-Induced Obese Mice
| Autor: | Keqiang Ye, Reed Otten, Shuai Zhang, Margaret C.L. Tse, Xia Liu, Robin H Schmidt, Liegang Liu, Chi Bun Chan |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Agonist
Male medicine.medical_specialty medicine.drug_class Clinical Biochemistry Tropomyosin receptor kinase B Biology 7 8-Dihydroxyflavone Biochemistry Article Neurotrophic factors Internal medicine Drug Discovery medicine Animals Humans Obesity Molecular Biology Pharmacology Membrane Glycoproteins AMPK General Medicine Flavones Thermogenin Endocrinology nervous system Knockout mouse Molecular Medicine Female Diet-induced obese |
| Popis: | SummaryChronic 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. |
| Databáze: | OpenAIRE |
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