Yamazaki Tomoo, Cable Edward E, Schnabl Bernd
Department of Medicine, University of California San Diego, La Jolla, California, USA.
Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, Japan.
Hepatol Commun. 2025 Feb 3;9(2). doi: 10.1097/HC9.0000000000000646. eCollection 2025 Feb 1.
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors involved in transcriptional regulation and play an important role in many physiological and metabolic processes. Unlike PPAR-alpha and PPAR-gamma, PPAR-delta is ubiquitously expressed, and its activity is key to maintaining proper metabolic homeostasis within the liver. PPAR-delta not only regulates physiologic processes of lipid, glucose, and bile acid metabolism but also attenuates pathologic responses to alcohol metabolism, inflammation, fibrosis, and carcinogenesis, and is considered an important therapeutic target in liver diseases. Promising results have been reported in clinical trials for PPAR-delta agonists in liver disease, and the selective agonist seladelpar was recently conditionally approved in the United States as a new treatment option for primary biliary cholangitis. This review provides an overview of PPAR-delta's function and biology in the liver, examines its kinetics and therapeutic potential across different liver diseases, and discusses the current status of clinical trials involving its agonists.
过氧化物酶体增殖物激活受体（PPARs）是参与转录调控的核受体，在许多生理和代谢过程中发挥重要作用。与PPAR-α和PPAR-γ不同，PPAR-δ在全身广泛表达，其活性是维持肝脏内适当代谢稳态的关键。PPAR-δ不仅调节脂质、葡萄糖和胆汁酸代谢的生理过程，还减轻对酒精代谢、炎症、纤维化和致癌作用的病理反应，被认为是肝脏疾病的重要治疗靶点。在肝脏疾病中PPAR-δ激动剂的临床试验已报告了有前景的结果，选择性激动剂塞拉德尔帕最近在美国被有条件批准作为原发性胆汁性胆管炎的一种新治疗选择。本综述概述了PPAR-δ在肝脏中的功能和生物学特性，研究其在不同肝脏疾病中的动力学和治疗潜力，并讨论了涉及其激动剂的临床试验现状。
