Muscle-generated BDNF is a sexually dimorphic myokine that controls metabolic flexibility.

Muscle-generated BDNF is a sexually dimorphic myokine that controls metabolic flexibility. Sci Signal. 2019 Aug 13;12(594): 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 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-1α 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 metabo...
Source: Science Signaling - Category: Biomedical Science Authors: Tags: Sci Signal Source Type: research