CHRONO-BMAL1通路调节骨骼肌糖代谢及其影响有氧运动能力的分子机制

骨骼肌糖代谢水平是影响有氧运动能力重要因素。已知生物节律调节关键分子BMAL1可直接调控骨骼肌糖代谢，CHRONO是近年来发现的BMAL1转录阻遏因子，CHRONO-BMAL1是调节生物节律的重要通路。然而，CHRONO-BMAL1通路调节骨骼肌糖代谢及其影响有氧运动能力研究，目前尚属空白。课题组前期研究发现Chrono基因过表达对骨骼肌糖代谢和有氧运动能力有负调节作用。.本项目在预实验和文献基础上，建立诱导型骨骼肌特异性Chrono转基因和诱导型骨骼肌特异性Chrono敲除小鼠，形成CHRONO功能获得和功能缺失对比研究模型，试图明确CHRONO-BMAL1通路对骨骼肌糖代谢调节作用，揭示CHRONO-BMAL1调节小鼠骨骼肌糖代谢及其影响有氧运动能力分子机制。本研究为阐明调节骨骼肌糖代谢与影响骨骼肌健康的新机制提供理论依据。

The level of glucose metabolism is an essential factor affecting aerobic exercise capacity. BMAL1 (Brain and Muscle Arnt-Like protein1), a key molecule in the regulation of biological rhythms, can directly regulate glucose metabolism in skeletal muscle. It has been reported that CHRONO (Computationally Highlighted Repressor Of the Network Oscillator) is a newly discovered repressor of BMAL1, and CHRONO-BMAL1 is an important pathway to regulate circadian oscillations, but whether the pathway regulates glucose metabolism in skeletal muscle is not clear. Our previous research found that Chrono overexpression has negative regulation effects on glucose utilization of skeletal muscle and endurance exercise capacity in mice. However, the molecular mechanism needs to be investigated. .On the basis of prophase work and references, we generated the inducible muscle-specific Chrono transgenic mice and inducible muscle-specific Chrono knockout mice to establish the animal models of function gain and function loss for contrast research. The molecular mechanism about the CHRONO-BMAL1 pathway regulating glucose metabolism in skeletal muscles and its effects on endurance exercise capacity in adult mice would be explored.