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Publication
Muscle-generated BDNF is a sexually dimorphic myokine that controls metabolic
flexibility.
Authors Yang X, Brobst D, Chan WS, Tse MCL, Herlea-Pana O, Ahuja P, Bi X, Zaw AM, Kwong
ZSW, Jia WH, Zhang ZG, Zhang N, Chow SKH, Cheung WH, Louie JCY, Griffin TM, Nong
W, Hui JHL, Du GH, Noh HL, Saengnipanthkul S, Chow BKC, Kim JK, Lee CW, Chan CB
Submitted By Submitted Externally on 4/30/2020
Status Published
Journal Science signaling
Year 2019
Date Published 8/1/2019
Volume : Pages 12 : Not Specified
PubMed Reference 31409756
Abstract The ability of skeletal muscle to switch between lipid and glucose oxidation for
ATP production during metabolic stress is pivotal for maintaining systemic
energy homeostasis, and dysregulation of this metabolic flexibility is a
dominant cause of several metabolic disorders. However, the molecular mechanism
that governs fuel selection in muscle is not well understood. Here, we report
that brain-derived neurotrophic factor (BDNF) is a fasting-induced myokine that
controls metabolic reprograming through the AMPK/CREB/PGC-1a pathway in female
mice. Female mice with a muscle-specific deficiency in BDNF (MBKO mice) were
unable to switch the predominant fuel source from carbohydrates to fatty acids
during fasting, which reduced ATP production in muscle. Fasting-induced muscle
atrophy was also compromised in female MBKO mice, likely a result of autophagy
inhibition. These mutant mice displayed myofiber necrosis, weaker muscle
strength, reduced locomotion, and muscle-specific insulin resistance. Together,
our results show that muscle-derived BDNF facilitates metabolic adaption during
nutrient scarcity in a gender-specific manner and that insufficient BDNF
production in skeletal muscle promotes the development of metabolic myopathies
and insulin resistance.




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