Peroxisome proliferator–activated receptor delta and liver diseases

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 pr...

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Main Authors: Tomoo Yamazaki, Edward E. Cable, Bernd Schnabl
Format: Article
Language:English
Published: Wolters Kluwer Health/LWW 2025-02-01
Series:Hepatology Communications
Online Access:http://journals.lww.com/10.1097/HC9.0000000000000646
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author Tomoo Yamazaki
Edward E. Cable
Bernd Schnabl
author_facet Tomoo Yamazaki
Edward E. Cable
Bernd Schnabl
author_sort Tomoo Yamazaki
collection DOAJ
description 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.
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institution Kabale University
issn 2471-254X
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publishDate 2025-02-01
publisher Wolters Kluwer Health/LWW
record_format Article
series Hepatology Communications
spelling doaj-art-9d60aeeeaf8f41ae8cf50a544ad3f5e62025-02-05T02:11:00ZengWolters Kluwer Health/LWWHepatology Communications2471-254X2025-02-019210.1097/HC9.0000000000000646HC90000000000000646Peroxisome proliferator–activated receptor delta and liver diseasesTomoo Yamazaki0Edward E. Cable1Bernd Schnabl2 1 Department of Medicine, University of California San Diego, La Jolla, California, USA 3 CymaBay Therapeutics, Fremont, California, USA 1 Department of Medicine, University of California San Diego, La Jolla, California, USAPeroxisome 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.http://journals.lww.com/10.1097/HC9.0000000000000646
spellingShingle Tomoo Yamazaki
Edward E. Cable
Bernd Schnabl
Peroxisome proliferator–activated receptor delta and liver diseases
Hepatology Communications
title Peroxisome proliferator–activated receptor delta and liver diseases
title_full Peroxisome proliferator–activated receptor delta and liver diseases
title_fullStr Peroxisome proliferator–activated receptor delta and liver diseases
title_full_unstemmed Peroxisome proliferator–activated receptor delta and liver diseases
title_short Peroxisome proliferator–activated receptor delta and liver diseases
title_sort peroxisome proliferator activated receptor delta and liver diseases
url http://journals.lww.com/10.1097/HC9.0000000000000646
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AT edwardecable peroxisomeproliferatoractivatedreceptordeltaandliverdiseases
AT berndschnabl peroxisomeproliferatoractivatedreceptordeltaandliverdiseases