Background

As a result of a sedentary lifestyle and excess food consumption in modern society, non-alcoholic fatty liver disease (NAFLD) characterized by fat accumulation in the liver is becoming a major disease burden. Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD, characterized by inflammation and fibrosis which can lead to hepatocellular carcinoma and liver failure. Nuclear receptors (NRs) are a family of ligand-regulated transcription factors which closely control multiple aspects of metabolism, and their transcriptional activity is modulated by various ligands, including hormones and lipids. Thus, NRs serve as potential pharmacological targets for NAFLD/NASH and other metabolic diseases.

Scope of Review

In this review, we provide a comprehensive overview of NRs that have been studied in the context of NAFLD/NASH with a focus on their transcriptional regulation, function in pre-clinical models, and studies of their clinical utility.

Major Conclusions

The transcriptional regulation of NRs is context-dependent. During the dynamic progression of NAFLD/NASH, NRs play diverse roles in multiple organs and different cell types in the liver, which highlights the necessity of targeting NRs in a stage-specific and cell-type specific manner to enhance the efficacy and safety of treatment methods.

中文翻译：

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非酒精性脂肪肝的核受体和转录调控

背景

由于现代社会久坐不动的生活方式和过量的食物消耗，以肝脏中脂肪堆积为特征的非酒精性脂肪肝（NAFLD）正在成为主要的疾病负担。非酒精性脂肪性肝炎 (NASH) 是 NAFLD 的一种高级形式，其特征是炎症和纤维化，可导致肝细胞癌和肝功能衰竭。核受体 (NRs) 是一个由配体调节的转录因子家族，它们密切控制代谢的多个方面，其转录活性受各种配体的调节，包括激素和脂质。因此，NRs 可作为 NAFLD/NASH 和其他代谢疾病的潜在药理学靶点。

审查范围

在这篇综述中，我们全面概述了在 NAFLD/NASH 的背景下研究过的 NR，重点是它们的转录调控、临床前模型中的功能以及它们的临床效用研究。

主要结论

NRs 的转录调控是上下文相关的。在 NAFLD/NASH 的动态进展过程中，NRs 在肝脏的多个器官和不同细胞类型中发挥着不同的作用，这凸显了以特定阶段和细胞类型的方式靶向 NRs 以提高治疗疗效和安全性的必要性方法。