Hunan Provincial Key Laboratory of Nutrition and Quality Control of Aquatic Animals, College of Biological and Chemical Engineering, Changsha University, Changsha410022, People's Republic of China.
College of Animal Science and Technology, Hunan Agricultural University, Changsha410128, People's Republic of China.
Br J Nutr. 2023 Aug 28;130(4):604-615. doi: 10.1017/S0007114522003646. Epub 2022 Nov 14.
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 and is highly responsive to short-term fasting in fast muscle of , and the correlation coefficient between and expression is enhanced after fasting treatment. Furthermore, we demonstrate that the transcriptional expression of is regulated by Clock, and the transcriptional expression of is regulated by KLF15 by using dual-luciferase reporter gene assay and -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 expression through affecting the rhythmic expression of , and then KLF15 promotes the transcription of to enhance the metabolism of BCAA, thus maintaining energy homoeostasis and providing energy for skeletal muscle as well as other tissues.
作为内部计时机制,生物钟在响应营养变化时对维持体内平衡起着至关重要的作用;同时,骨骼肌中的支链氨基酸(BCAA)在禁食期间对维持能量平衡起着重要作用。我们实验室的先前研究结果表明,禁食可以影响鱼类的外周生物钟和 BCAA 代谢,但生物钟和 BCAA 代谢之间的关系,以及生物钟是否通过调节 BCAA 代谢来维持禁食期间的生理平衡仍不清楚。本研究表明,十五个核心时钟基因和 和 的表达对 的快速肌的短期禁食高度敏感,并且禁食处理后 和 表达之间的相关系数增强。此外,我们通过双荧光素酶报告基因检测和 -morpholino 介导的基因敲低技术证明了 Clock 调节 的转录表达,而 KLF15 调节 的转录表达。因此,禁食对生物钟和 BCAA 代谢途径之间的转录产生了动态协调。这些发现强调了生物钟和 BCAA 代谢之间的相互作用,并表明禁食通过影响 的节律表达来诱导 表达的转变,然后 KLF15 促进 的转录以增强 BCAA 的代谢,从而维持能量平衡并为骨骼肌以及其他组织提供能量。