Peroxisome proliferator-activated receptors and their novel ligands as candidates for the treatment of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a major health issue worldwide, frequently associated with obesity and type 2 diabetes. Steatosis is the initial stage of the disease, which is characterized by lipid accumulation in hepatocytes, which can progress to non-alcoholic steatohepatitis (NASH)...

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Main Authors: Fougerat, Anne, Montagner, Alexandra, Loiseau, Nicolas, Guillou, Hervé, Wahli, Walter
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2020
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Online Access:https://hdl.handle.net/10356/144925
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spelling sg-ntu-dr.10356-1449252023-03-05T16:47:08Z Peroxisome proliferator-activated receptors and their novel ligands as candidates for the treatment of non-alcoholic fatty liver disease Fougerat, Anne Montagner, Alexandra Loiseau, Nicolas Guillou, Hervé Wahli, Walter Lee Kong Chian School of Medicine (LKCMedicine) Science::Medicine Peroxisome Proliferator-activated Receptors Synthetic Agonists Non-alcoholic fatty liver disease (NAFLD) is a major health issue worldwide, frequently associated with obesity and type 2 diabetes. Steatosis is the initial stage of the disease, which is characterized by lipid accumulation in hepatocytes, which can progress to non-alcoholic steatohepatitis (NASH) with inflammation and various levels of fibrosis that further increase the risk of developing cirrhosis and hepatocellular carcinoma. The pathogenesis of NAFLD is influenced by interactions between genetic and environmental factors and involves several biological processes in multiple organs. No effective therapy is currently available for the treatment of NAFLD. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate many functions that are disturbed in NAFLD, including glucose and lipid metabolism, as well as inflammation. Thus, they represent relevant clinical targets for NAFLD. In this review, we describe the determinants and mechanisms underlying the pathogenesis of NAFLD, its progression and complications, as well as the current therapeutic strategies that are employed. We also focus on the complementary and distinct roles of PPAR isotypes in many biological processes and on the effects of first-generation PPAR agonists. Finally, we review novel and safe PPAR agonists with improved efficacy and their potential use in the treatment of NAFLD. Published version 2020-12-03T05:47:38Z 2020-12-03T05:47:38Z 2020 Journal Article Fougerat, A., Montagner, A., Loiseau, N., Guillou, H., & Wahli, W. (2020). Peroxisome Proliferator-Activated Receptors and Their Novel Ligands as Candidates for the Treatment of Non-Alcoholic Fatty Liver Disease. Cells, 9(7), 1638-. doi:10.3390/cells9071638 0092-8674 https://hdl.handle.net/10356/144925 10.3390/cells9071638 32650421 7 9 en Cells © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution(CC BY) license (http://creativecommons.org/licenses/by/4.0/). application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
Peroxisome Proliferator-activated Receptors
Synthetic Agonists
spellingShingle Science::Medicine
Peroxisome Proliferator-activated Receptors
Synthetic Agonists
Fougerat, Anne
Montagner, Alexandra
Loiseau, Nicolas
Guillou, Hervé
Wahli, Walter
Peroxisome proliferator-activated receptors and their novel ligands as candidates for the treatment of non-alcoholic fatty liver disease
description Non-alcoholic fatty liver disease (NAFLD) is a major health issue worldwide, frequently associated with obesity and type 2 diabetes. Steatosis is the initial stage of the disease, which is characterized by lipid accumulation in hepatocytes, which can progress to non-alcoholic steatohepatitis (NASH) with inflammation and various levels of fibrosis that further increase the risk of developing cirrhosis and hepatocellular carcinoma. The pathogenesis of NAFLD is influenced by interactions between genetic and environmental factors and involves several biological processes in multiple organs. No effective therapy is currently available for the treatment of NAFLD. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate many functions that are disturbed in NAFLD, including glucose and lipid metabolism, as well as inflammation. Thus, they represent relevant clinical targets for NAFLD. In this review, we describe the determinants and mechanisms underlying the pathogenesis of NAFLD, its progression and complications, as well as the current therapeutic strategies that are employed. We also focus on the complementary and distinct roles of PPAR isotypes in many biological processes and on the effects of first-generation PPAR agonists. Finally, we review novel and safe PPAR agonists with improved efficacy and their potential use in the treatment of NAFLD.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Fougerat, Anne
Montagner, Alexandra
Loiseau, Nicolas
Guillou, Hervé
Wahli, Walter
format Article
author Fougerat, Anne
Montagner, Alexandra
Loiseau, Nicolas
Guillou, Hervé
Wahli, Walter
author_sort Fougerat, Anne
title Peroxisome proliferator-activated receptors and their novel ligands as candidates for the treatment of non-alcoholic fatty liver disease
title_short Peroxisome proliferator-activated receptors and their novel ligands as candidates for the treatment of non-alcoholic fatty liver disease
title_full Peroxisome proliferator-activated receptors and their novel ligands as candidates for the treatment of non-alcoholic fatty liver disease
title_fullStr Peroxisome proliferator-activated receptors and their novel ligands as candidates for the treatment of non-alcoholic fatty liver disease
title_full_unstemmed Peroxisome proliferator-activated receptors and their novel ligands as candidates for the treatment of non-alcoholic fatty liver disease
title_sort peroxisome proliferator-activated receptors and their novel ligands as candidates for the treatment of non-alcoholic fatty liver disease
publishDate 2020
url https://hdl.handle.net/10356/144925
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