Hussain Yusuf, Dar Mohammad Irfan, Pan Xiaoyue
Department of Foundations of Medicine, New York University Grossman Long Island School of Medicine, Mineola, NY 11501, USA.
Diabetes and Obesity Research Center, NYU Langone Hospital-Long Island, Mineola, NY 11501, USA.
Metabolites. 2024 Dec 22;14(12):723. doi: 10.3390/metabo14120723.
Circadian rhythms are intrinsic, 24 h cycles that regulate key physiological, mental, and behavioral processes, including sleep-wake cycles, hormone secretion, and metabolism. These rhythms are controlled by the brain's suprachiasmatic nucleus, which synchronizes with environmental signals, such as light and temperature, and consequently maintains alignment with the day-night cycle. Molecular feedback loops, driven by core circadian "clock genes", such as Clock, Bmal1, Per, and Cry, are essential for rhythmic gene expression; disruptions in these feedback loops are associated with various health issues. Dysregulated lipid metabolism in the brain has been implicated in the pathogenesis of neurological disorders by contributing to oxidative stress, neuroinflammation, and synaptic dysfunction, as observed in conditions such as Alzheimer's and Parkinson's diseases. Disruptions in circadian gene expression have been shown to perturb lipid regulatory mechanisms in the brain, thereby triggering neuroinflammatory responses and oxidative damage. This review synthesizes current insights into the interconnections between circadian rhythms and lipid metabolism, with a focus on their roles in neurological health and disease. It further examines how the desynchronization of circadian genes affects lipid metabolism and explores the potential mechanisms through which disrupted circadian signaling might contribute to the pathophysiology of neurodegenerative disorders.
昼夜节律是内在的24小时周期,调节关键的生理、心理和行为过程,包括睡眠-觉醒周期、激素分泌和新陈代谢。这些节律由大脑的视交叉上核控制,该核与环境信号(如光和温度)同步,从而与昼夜周期保持一致。由核心昼夜节律“时钟基因”(如Clock、Bmal1、Per和Cry)驱动的分子反馈回路对于节律性基因表达至关重要;这些反馈回路的破坏与各种健康问题相关。大脑中脂质代谢失调通过导致氧化应激、神经炎症和突触功能障碍,在神经疾病的发病机制中起作用,如在阿尔茨海默病和帕金森病等病症中所见。昼夜节律基因表达的破坏已被证明会扰乱大脑中的脂质调节机制,从而引发神经炎症反应和氧化损伤。本综述综合了目前对昼夜节律与脂质代谢之间相互联系的见解,重点关注它们在神经健康和疾病中的作用。它进一步研究了昼夜节律基因的不同步如何影响脂质代谢,并探讨了昼夜节律信号破坏可能导致神经退行性疾病病理生理的潜在机制。
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