PDF(Pubmed)
Abstract：
A growing body of research has identified circadian-rhythm disruption as a risk factor for metabolic health. However, the underlying biological basis remains complex, and complete molecular mechanisms are unknown. There is emerging evidence from animal and human research to suggest that the expression of core circadian genes, such as circadian locomotor output cycles kaput gene (CLOCK), brain and muscle ARNT-Like 1 gene (BMAL1), period (PER), and cyptochrome (CRY), and the consequent expression of hundreds of circadian output genes are integral to the regulation of cellular metabolism. These circadian mechanisms represent potential pathophysiological pathways linking circadian disruption to adverse metabolic health outcomes, including obesity, metabolic syndrome, and type 2 diabetes. Here, we aim to summarize select evidence from in vivo animal models and compare these results with epidemiologic research findings to advance understanding of existing foundational evidence and potential mechanistic links between circadian disruption and altered clock gene expression contributions to metabolic health-related pathologies. Findings have important implications for the treatment, prevention, and control of metabolic pathologies underlying leading causes of death and disability, including diabetes, cardiovascular disease, and cancer.
摘要：
越来越多的研究已经确定昼夜节律破坏是代谢健康的危险因素。然而,潜在的生物学基础仍然很复杂，和完整的分子机制是未知的。来自动物和人类研究的新证据表明，核心昼夜节律基因的表达，如昼夜节律运动输出周期kaput基因(CLOCK)，大脑和肌肉ARNT样1基因（BMAL1），期间（PER），和cyptochrome（CRY），数百种昼夜节律输出基因的表达对细胞代谢的调节是不可或缺的。这些昼夜节律机制代表了将昼夜节律破坏与不良代谢健康结果联系起来的潜在病理生理学途径。包括肥胖,代谢综合征,和2型糖尿病。这里,我们旨在总结体内动物模型的部分证据,并将这些结果与流行病学研究结果进行比较,以加深对现有基础证据以及昼夜节律中断和生物钟基因表达改变对代谢健康相关病理的贡献之间潜在机制联系的理解.研究结果对治疗有重要意义，预防,以及控制导致死亡和残疾的主要原因的代谢病理学，包括糖尿病,心血管疾病,和癌症。
