Duez Hélène, Staels Bart
Institut Pasteur de Lille, Lille F-59019, France.
FEBS Lett. 2008 Jan 9;582(1):19-25. doi: 10.1016/j.febslet.2007.08.032. Epub 2007 Aug 24.
Normal physiological processes are under control of circadian rhythms. Moreover, certain pathological events, such as cardiovascular accidents (myocardial infarction, stroke) occur more frequently at specific times of the day. Recent observations demonstrate a causal relationship between alterations in circadian rhythmicity and metabolic disorders. Disruption of clock genes results in dyslipidemia, insulin resistance and obesity, all predisposing to atherosclerosis. The nuclear receptor Rev-erb alpha is part of the clock circuitry and plays an important role in keeping proper timing of the clock. Rev-erb alpha also regulates lipid metabolism, adipogenesis and vascular inflammation. Interestingly, Rev-erb alpha also cross-talks with several other nuclear receptors involved in energy homeostasis. Therefore Rev-erb alpha may serve to couple metabolic and circadian signals.
正常生理过程受昼夜节律控制。此外,某些病理事件,如心血管意外(心肌梗死、中风)在一天中的特定时间更频繁发生。最近的观察表明昼夜节律改变与代谢紊乱之间存在因果关系。生物钟基因的破坏会导致血脂异常、胰岛素抵抗和肥胖,所有这些都易引发动脉粥样硬化。核受体Rev-erbα是生物钟回路的一部分,在维持生物钟的正常节律方面发挥重要作用。Rev-erbα还调节脂质代谢、脂肪生成和血管炎症。有趣的是,Rev-erbα还与其他几个参与能量稳态的核受体相互作用。因此,Rev-erbα可能有助于耦合代谢和昼夜信号。