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Anti-NASH Drug Development Hitches a Lift on PPAR Agonism

Department of In Vitro Toxicology & Dermato-Cosmetology (IVTD), Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel (VUB); Laarbeeklaan 103, 1090 Brussels, Belgium
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Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(1), 37; https://doi.org/10.3390/cells9010037
Received: 25 November 2019 / Revised: 15 December 2019 / Accepted: 17 December 2019 / Published: 21 December 2019
(This article belongs to the Special Issue Recent Advances in Liver Repair Strategies)
Non-alcoholic fatty liver disease (NAFLD) affects one-third of the population worldwide, of which a substantial number of patients suffer from non-alcoholic steatohepatitis (NASH). NASH is a severe condition characterized by steatosis and concomitant liver inflammation and fibrosis, for which no drug is yet available. NAFLD is also generally conceived as the hepatic manifestation of the metabolic syndrome. Consequently, well-established drugs that are indicated for the treatment of type 2 diabetes and hyperlipidemia are thought to exert effects that alleviate the pathological features of NASH. One class of these drugs targets peroxisome proliferator-activated receptors (PPARs), which are nuclear receptors that play a regulatory role in lipid metabolism and inflammation. Therefore, PPARs are now also being investigated as potential anti-NASH druggable targets. In this paper, we review the mechanisms of action and physiological functions of PPARs and discuss the position of the different PPAR agonists in the therapeutic landscape of NASH. We particularly focus on the PPAR agonists currently under evaluation in clinical phase II and III trials. Preclinical strategies and how refinement and optimization may improve PPAR-targeted anti-NASH drug testing are also discussed. Finally, potential caveats related to PPAR agonism in anti-NASH therapy are stipulated. View Full-Text
Keywords: non-alcoholic steatohepatitis (NASH); non-alcoholic fatty liver disease (NAFLD); peroxisome proliferator-activated receptor (PPAR); elafibranor; lanifibranor; saroglitazar; pioglitazone non-alcoholic steatohepatitis (NASH); non-alcoholic fatty liver disease (NAFLD); peroxisome proliferator-activated receptor (PPAR); elafibranor; lanifibranor; saroglitazar; pioglitazone
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MDPI and ACS Style

Boeckmans, J.; Natale, A.; Rombaut, M.; Buyl, K.; Rogiers, V.; De Kock, J.; Vanhaecke, T.; Rodrigues, R.M. Anti-NASH Drug Development Hitches a Lift on PPAR Agonism. Cells 2020, 9, 37.

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