Saran Anand R, Dave Shravan, Zarrinpar Amir
Division of Gastroenterology, University of California, San Diego, La Jolla, California.
Division of Gastroenterology, University of California, San Diego, La Jolla, California; Veterans Affairs Health Sciences San Diego, La Jolla, California; Institute of Diabetes and Metabolic Health, University of California, San Diego, La Jolla, California; Center for Microbiome Innovation, University of California, San Diego, La Jolla, California.
Gastroenterology. 2020 May;158(7):1948-1966.e1. doi: 10.1053/j.gastro.2020.01.050. Epub 2020 Feb 13.
Circadian clock proteins are endogenous timing mechanisms that control the transcription of hundreds of genes. Their integral role in coordinating metabolism has led to their scrutiny in a number of diseases, including nonalcoholic fatty liver disease (NAFLD). Discoordination between central and peripheral circadian rhythms is a core feature of nearly every genetic, dietary, or environmental model of metabolic syndrome and NAFLD. Restricting feeding to a defined daily interval (time-restricted feeding) can synchronize the central and peripheral circadian rhythms, which in turn can prevent or even treat the metabolic syndrome and hepatic steatosis. Importantly, a number of proteins currently under study as drug targets in NAFLD (sterol regulatory element-binding protein [SREBP], acetyl-CoA carboxylase [ACC], peroxisome proliferator-activator receptors [PPARs], and incretins) are modulated by circadian proteins. Thus, the clock can be used to maximize the benefits and minimize the adverse effects of pharmaceutical agents for NAFLD. The circadian clock itself has the potential for use as a target for the treatment of NAFLD.
昼夜节律蛋白是控制数百种基因转录的内源性计时机制。它们在协调新陈代谢中的重要作用使其在包括非酒精性脂肪性肝病（NAFLD）在内的多种疾病中受到审视。中枢和外周昼夜节律之间的失调是几乎所有代谢综合征和NAFLD的遗传、饮食或环境模型的核心特征。将进食限制在特定的每日时间段（限时进食）可以使中枢和外周昼夜节律同步，进而预防甚至治疗代谢综合征和肝脂肪变性。重要的是，目前作为NAFLD药物靶点正在研究的一些蛋白质（固醇调节元件结合蛋白[SREBP]、乙酰辅酶A羧化酶[ACC]、过氧化物酶体增殖物激活受体[PPARs]和肠促胰岛素）受昼夜节律蛋白调节。因此，生物钟可用于最大化治疗NAFLD药物的益处并最小化其不良反应。昼夜节律钟本身有潜力用作治疗NAFLD的靶点。
