The circadian rhythm regulates branched-chain amino acids metabolism in fast muscle of Chinese perch (Siniperca chuatsi) during short-term fasting by Clock-KLF15-Bcat2 pathway
The circadian rhythm regulates branched-chain amino acids metabolism in fast muscle of Chinese perch (Siniperca chuatsi) during short-term fasting by Clock-KLF15-Bcat2 pathway
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DOI：
10.1017/s0007114522003646
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发表时间：
2022-11
影响因子：
3.6
通讯作者：
Xin Zhu;Jingjie Liu;Minglang Cai;Lingsheng Bao;Yaxiong Pan;Ping Wu;W. Chu;Jianshe Zhang
中科院分区：
文献类型：
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作者：
Xin Zhu;Jingjie Liu;Minglang Cai;Lingsheng Bao;Yaxiong Pan;Ping Wu;W. Chu;Jianshe Zhang
摘要昼夜节律作为一种内在的时间保持机制，在维持机体对营养变化的稳态反应中起着至关重要的作用;同时，骨骼肌中的支链氨基酸（BCAA）在维持禁食期间的能量稳态中起着重要的作用。本实验室的前期研究结果表明，禁食可以影响鱼类的昼夜节律和BCAA代谢，但昼夜节律与BCAA代谢之间的关系，以及昼夜节律是否通过调节BCAA代谢来维持禁食过程中的生理稳态尚不清楚。本研究表明，禁食对中华鲟快肌中15个核心时钟基因以及KLF 15和Bcat 2的表达具有高度的响应性，禁食处理后Clock和KLF 15表达的相关系数增强。此外，我们还利用双荧光素酶报告基因分析和Vivo-morpholinos介导的基因敲低技术证实了KLF 15的转录表达受Clock的调控，而Bcat 2的转录表达受KLF 15的调控。因此，禁食在昼夜节律和BCAA代谢途径之间施加了转录的动态协调。这一发现凸显了昼夜节律与BCAA代谢之间的相互作用，提示禁食通过影响Clock的节律性表达，诱导KLF 15表达的转换，进而KLF 15促进Bcat 2的转录，增强BCAA的代谢，从而维持能量稳态，为骨骼肌等组织提供能量。
Abstract As an internal time-keeping mechanism, circadian rhythm plays crucial role in maintaining homoeostasis when in response to nutrition change; meanwhile, branched-chain amino acids (BCAA) in skeletal muscle play an important role in preserving energy homoeostasis during fasting. Previous results from our laboratory suggested that fasting can influence peripheral circadian rhythm and BCAA metabolism in fish, but the relationship between circadian rhythm and BCAA metabolism, and whether circadian rhythm regulates BCAA metabolism to maintain physiological homoeostasis during fasting remains unclear. This study shows that the expression of fifteen core clock genes as well as KLF15 and Bcat2 is highly responsive to short-term fasting in fast muscle of Siniperca chuatsi, and the correlation coefficient between Clock and KLF15 expression is enhanced after fasting treatment. Furthermore, we demonstrate that the transcriptional expression of KLF15 is regulated by Clock, and the transcriptional expression of Bcat2 is regulated by KLF15 by using dual-luciferase reporter gene assay and Vivo-morpholinos-mediated gene knockdown technique. Therefore, fasting imposes a dynamic coordination of transcription between the circadian rhythm and BCAA metabolic pathways. The findings highlight the interaction between circadian rhythm and BCAA metabolism and suggest that fasting induces a switch in KLF15 expression through affecting the rhythmic expression of Clock, and then KLF15 promotes the transcription of Bcat2 to enhance the metabolism of BCAA, thus maintaining energy homoeostasis and providing energy for skeletal muscle as well as other tissues.