Muscle-generated BDNF is a sexually dimorphic myokine that controls metabolic flexibility
Publication in refereed journal

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摘要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-1 alpha 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.
著者Yang, Brobst, Chan, Tse, Herlea-Pana, Ahuja, Bi, Zaw, Kwong, Jia, Zhang, Zhang, Chow, Cheung, Louie, Nong, Griffin, Du, Hui, Saengnipanthkul, Noh, Kim, Chow, Chan, Lee
期刊名稱Science Signaling
出版年份2019
月份8
日期13
卷號12
期次594
出版社American Association for the Advancement of Science
文章號碼eaau1468
國際標準期刊號1945-0877
電子國際標準期刊號1937-9145
語言英式英語

上次更新時間 2021-09-05 於 00:12