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

Chemistry & Biology
Chi Bun ChanKeqiang Ye

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.

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Citations

Jul 8, 2017·Experimental & Molecular Medicine·No-Joon SongKye Won Park
Feb 15, 2018·EMBO Reports·Aygul SubkhangulovaThomas E Willnow
Jul 18, 2019·Clinical and Experimental Pharmacology & Physiology·Li MaBaoguo He
Oct 30, 2019·Current Topics in Medicinal Chemistry·Chi Bun ChanKeqiang Ye
Sep 12, 2020·Critical Reviews in Food Science and Nutrition·Marco EmiliFiorenza Stagni
Sep 30, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Qing Ou-YangLei Chen
Nov 22, 2016·Journal of Neuroscience Research·Chi Bun Chan, Keqiang Ye
Oct 19, 2020·Biochemical and Biophysical Research Communications·Ryan Antony, Yifan Li
Jan 21, 2021·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Melise M EdwardsJames E Blevins
Jun 19, 2021·Proceedings of the National Academy of Sciences of the United States of America·Zhourui WuKeqiang Ye
Nov 20, 2021·ACS Medicinal Chemistry Letters·Govindan SubramanianAndrea J Gonzales

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