Exercise-induced BDNF promotes PPARδ-dependent reprogramming of lipid metabolism in skeletal muscle during exercise recovery

IF 6.7 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Science Signaling Pub Date : 2024-03-19 DOI:https://www.science.org/doi/10.1126/scisignal.adh2783

Wing Suen Chan, Chun Fai Ng, Brian Pak Shing Pang, Miaojia Hang, Margaret Chui Ling Tse, Elsie Chit Yu Iu, Xin Ci Ooi, Xiuying Yang, Jason K. Kim, Chi Wai Lee, Chi Bun Chan

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Abstract

Post-exercise recovery is essential to resolve metabolic perturbations and promote long-term cellular remodeling in response to exercise. Here, we report that muscle-generated brain-derived neurotrophic factor (BDNF) elicits post-exercise recovery and metabolic reprogramming in skeletal muscle. BDNF increased the post-exercise expression of the gene encoding PPARδ (peroxisome proliferator–activated receptor δ), a transcription factor that is a master regulator of lipid metabolism. After exercise, mice with muscle-specific Bdnf knockout (MBKO) exhibited impairments in PPARδ-regulated metabolic gene expression, decreased intramuscular lipid content, reduced β-oxidation, and dysregulated mitochondrial dynamics. Moreover, MBKO mice required a longer period to recover from a bout of exercise and did not show increases in exercise-induced endurance capacity. Feeding naïve mice with the bioavailable BDNF mimetic 7,8-dihydroxyflavone resulted in effects that mimicked exercise-induced adaptations, including improved exercise capacity. Together, our findings reveal that BDNF is an essential myokine for exercise-induced metabolic recovery and remodeling in skeletal muscle.

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运动诱导的 BDNF 可促进运动恢复期骨骼肌脂质代谢的 PPARδ 依赖性重编程

运动后恢复对于解决代谢紊乱和促进长期细胞重塑以应对运动至关重要。在这里，我们报告了肌肉产生的脑源性神经营养因子（BDNF）能促进骨骼肌的运动后恢复和代谢重塑。BDNF 增加了运动后编码 PPARδ（过氧化物酶体增殖激活受体δ）基因的表达，PPARδ是一种转录因子，是脂质代谢的主要调节因子。运动后，肌肉特异性 Bdnf 基因敲除（MBKO）小鼠表现出 PPARδ 调节的代谢基因表达障碍、肌肉内脂质含量降低、β 氧化减少以及线粒体动力学失调。此外，MBKO 小鼠需要更长的时间才能从运动中恢复过来，而且运动诱导的耐力能力也没有提高。用生物可利用的 BDNF 模拟物 7,8-二羟基黄酮喂养天真小鼠会产生模拟运动诱导适应的效果，包括提高运动能力。总之，我们的研究结果表明，BDNF 是运动诱导的骨骼肌代谢恢复和重塑所必需的肌动素。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Signaling BIOCHEMISTRY & MOLECULAR BIOLOGY-CELL BIOLOGY

CiteScore

9.50

自引率

0.00%

发文量

148

审稿时长

3-8 weeks

期刊介绍： "Science Signaling" is a reputable, peer-reviewed journal dedicated to the exploration of cell communication mechanisms, offering a comprehensive view of the intricate processes that govern cellular regulation. This journal, published weekly online by the American Association for the Advancement of Science (AAAS), is a go-to resource for the latest research in cell signaling and its various facets. The journal's scope encompasses a broad range of topics, including the study of signaling networks, synthetic biology, systems biology, and the application of these findings in drug discovery. It also delves into the computational and modeling aspects of regulatory pathways, providing insights into how cells communicate and respond to their environment. In addition to publishing full-length articles that report on groundbreaking research, "Science Signaling" also features reviews that synthesize current knowledge in the field, focus articles that highlight specific areas of interest, and editor-written highlights that draw attention to particularly significant studies. This mix of content ensures that the journal serves as a valuable resource for both researchers and professionals looking to stay abreast of the latest advancements in cell communication science.