肝芳香烃受体在非酒精性脂肪肝中的作用

Receptors (Basel, Switzerland) Pub Date : 2023-03-01 Epub Date: 2023-01-04 DOI:10.3390/receptors2010001
Nikhil Y Patil, Jacob E Friedman, Aditya D Joshi
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摘要

在非酒精性脂肪肝(NAFLD)的背景下,人们对许多核受体进行了广泛的研究,其中包括类法尼X受体、肝X受体、过氧化物酶体增殖激活受体、孕烷X受体和肝核因子。继 20 世纪 70 年代首次描述芳基烃受体(AhR)之后,数十年的研究揭示了它在毒性和病理生理过程中的作用,但 AhR 在非酒精性脂肪肝中的功能意义尚未完全解开。最近,多个研究小组利用大量模拟非酒精性脂肪肝病理的体外和体内模型来研究 AhR 在脂肪肝中的功能意义。本综述全面介绍了有关 AhR 在非酒精性脂肪肝中的有益作用和可能的有害作用的研究。本文讨论了如何合理解释 AhR 在非酒精性脂肪肝中作为 "双刃剑 "的悖论。最后,了解AhR配体及其在非酒精性脂肪肝中的信号传导,将有助于我们在不久的将来将AhR作为潜在的药物靶点来设计治疗非酒精性脂肪肝的创新疗法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Role of Hepatic Aryl Hydrocarbon Receptor in Non-Alcoholic Fatty Liver Disease.

Numerous nuclear receptors including farnesoid X receptor, liver X receptor, peroxisome proliferator-activated receptors, pregnane X receptor, hepatic nuclear factors have been extensively studied within the context of non-alcoholic fatty liver disease (NAFLD). Following the first description of the Aryl hydrocarbon Receptor (AhR) in the 1970s and decades of research which unveiled its role in toxicity and pathophysiological processes, the functional significance of AhR in NAFLD has not been completely decoded. Recently, multiple research groups have utilized a plethora of in vitro and in vivo models that mimic NAFLD pathology to investigate the functional significance of AhR in fatty liver disease. This review provides a comprehensive account of studies describing both the beneficial and possible detrimental role of AhR in NAFLD. A plausible reconciliation for the paradox indicating AhR as a 'double-edged sword' in NAFLD is discussed. Finally, understanding AhR ligands and their signaling in NAFLD will facilitate us to probe AhR as a potential drug target to design innovative therapeutics against NAFLD in the near future.

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