An Overview of the Role of Peroxisome Proliferator-activated Receptors in Liver Diseases

Overview

Journal J Clin Transl Hepatol

Specialty Gastroenterology

Date 2024 Jan 1

PMID 38161499

Authors

Zahra Changizi

Forough Kajbaf

Azam Moslehi

Affiliations

Soon will be listed here.

Abstract

Peroxisome proliferator-activated receptors (PPARs) are a superfamily of nuclear transcription receptors, consisting of PPARα, PPARγ, and PPARβ/δ, which are highly expressed in the liver. They control and modulate the expression of a large number of genes involved in metabolism and energy homeostasis, oxidative stress, inflammation, and even apoptosis in the liver. Therefore, they have critical roles in the pathophysiology of hepatic diseases. This review provides a general insight into the role of PPARs in liver diseases and some of their agonists in the clinic.

Citing Articles

Distinct peroxisome populations differentially respond to alcohol-associated hepatic injury.

Mitra R, Adhikari R, Davis S, McVicker B, Tuma P Mol Biol Cell. 2024; 35(12):ar156.

PMID: 39535899 PMC: 11656475. DOI: 10.1091/mbc.E24-06-0252.

The Effect of Copper Nanoparticles on Liver Metabolism Depends on the Type of Dietary Fiber.

Marzec A, Fotschki B, Napiorkowska D, Fotschki J, Cholewinska E, Listos P Nutrients. 2024; 16(21).

PMID: 39519478 PMC: 11547515. DOI: 10.3390/nu16213645.

RAMP1 Protects Hepatocytes against Ischemia-reperfusion Injury by Inhibiting the ERK/YAP Pathway.

Tang Y, Yuan Z, Lu X, Song Y, Zhu S, Qiu C J Clin Transl Hepatol. 2024; 12(4):357-370.

PMID: 38638379 PMC: 11022058. DOI: 10.14218/JCTH.2023.00339.

References

Choudhary N, Kumar N, Duseja A . Peroxisome Proliferator-Activated Receptors and Their Agonists in Nonalcoholic Fatty Liver Disease. J Clin Exp Hepatol. 2020; 9(6):731-739. PMC: 6926194. DOI: 10.1016/j.jceh.2019.06.004. View

Knight B, Hebbachi A, Hauton D, Brown A, Wiggins D, Patel D . A role for PPARalpha in the control of SREBP activity and lipid synthesis in the liver. Biochem J. 2005; 389(Pt 2):413-21. PMC: 1175119. DOI: 10.1042/BJ20041896. View

Massip-Salcedo M, Zaouali M, Padrissa-Altes S, Casillas-Ramirez A, Rodes J, Rosello-Catafau J . Activation of peroxisome proliferator-activated receptor-alpha inhibits the injurious effects of adiponectin in rat steatotic liver undergoing ischemia-reperfusion. Hepatology. 2007; 47(2):461-72. DOI: 10.1002/hep.21935. View

McConnell B, Yang V . Mammalian Krüppel-like factors in health and diseases. Physiol Rev. 2010; 90(4):1337-81. PMC: 2975554. DOI: 10.1152/physrev.00058.2009. View

Castaneda D, Gonzalez A, Alomari M, Tandon K, Zervos X . From hepatitis A to E: A critical review of viral hepatitis. World J Gastroenterol. 2021; 27(16):1691-1715. PMC: 8072198. DOI: 10.3748/wjg.v27.i16.1691. View

Ye X, Zhang T, Han H . PPARα: A potential therapeutic target of cholestasis. Front Pharmacol. 2022; 13:916866. PMC: 9342652. DOI: 10.3389/fphar.2022.916866. View

Duscio L, Das P, Santhanam A, He T, Younkin S, Katusic Z . Activation of PPARδ prevents endothelial dysfunction induced by overexpression of amyloid-β precursor protein. Cardiovasc Res. 2012; 96(3):504-12. PMC: 3500044. DOI: 10.1093/cvr/cvs266. View

Sun J, Bian Y, Ma Y, Ali W, Wang T, Yuan Y . Melatonin alleviates cadmium-induced nonalcoholic fatty liver disease in ducks by alleviating autophagic flow arrest via PPAR-α and reducing oxidative stress. Poult Sci. 2023; 102(8):102835. PMC: 10404762. DOI: 10.1016/j.psj.2023.102835. View

Wang C, Li Z, Zhao B, Wu Y, Fu Y, Kang K . PGC-1 Protects against Hepatic Ischemia Reperfusion Injury by Activating PPAR and PPAR and Regulating ROS Production. Oxid Med Cell Longev. 2021; 2021:6677955. PMC: 8159639. DOI: 10.1155/2021/6677955. View

10.

Kim J, Wright H, Wright M, Spiegelman B . ADD1/SREBP1 activates PPARgamma through the production of endogenous ligand. Proc Natl Acad Sci U S A. 1998; 95(8):4333-7. PMC: 22489. DOI: 10.1073/pnas.95.8.4333. View

11.

Liao X, Wang Y, Wong C . Troglitazone induces cytotoxicity in part by promoting the degradation of peroxisome proliferator-activated receptor γ co-activator-1α protein. Br J Pharmacol. 2010; 161(4):771-81. PMC: 2992894. DOI: 10.1111/j.1476-5381.2010.00900.x. View

12.

Muzio G, Barrera G, Pizzimenti S . Peroxisome Proliferator-Activated Receptors (PPARs) and Oxidative Stress in Physiological Conditions and in Cancer. Antioxidants (Basel). 2021; 10(11). PMC: 8614822. DOI: 10.3390/antiox10111734. View

13.

Ozcan L, Tabas I . Role of endoplasmic reticulum stress in metabolic disease and other disorders. Annu Rev Med. 2012; 63:317-28. PMC: 3290993. DOI: 10.1146/annurev-med-043010-144749. View

14.

Park J, Kim J . Pathologic differential diagnosis of metastatic carcinoma in the liver. Clin Mol Hepatol. 2018; 25(1):12-20. PMC: 6435968. DOI: 10.3350/cmh.2018.0067. View

15.

Sun N, Shen C, Zhang L, Wu X, Yu Y, Yang X . Hepatic Krüppel-like factor 16 (KLF16) targets PPARα to improve steatohepatitis and insulin resistance. Gut. 2020; 70(11):2183-2195. PMC: 8515101. DOI: 10.1136/gutjnl-2020-321774. View

16.

Fougerat A, Schoiswohl G, Polizzi A, Regnier M, Wagner C, Smati S . ATGL-dependent white adipose tissue lipolysis controls hepatocyte PPARα activity. Cell Rep. 2022; 39(10):110910. DOI: 10.1016/j.celrep.2022.110910. View

17.

Peng L, Yang H, Ye Y, Ma Z, Kuhn C, Rahmeh M . Role of Peroxisome Proliferator-Activated Receptors (PPARs) in Trophoblast Functions. Int J Mol Sci. 2021; 22(1). PMC: 7795665. DOI: 10.3390/ijms22010433. View

18.

Monsalve F, Pyarasani R, Delgado-Lopez F, Moore-Carrasco R . Peroxisome proliferator-activated receptor targets for the treatment of metabolic diseases. Mediators Inflamm. 2013; 2013:549627. PMC: 3678499. DOI: 10.1155/2013/549627. View

19.

Monroy-Ramirez H, Galicia-Moreno M, Sandoval-Rodriguez A, Meza-Rios A, Santos A, Armendariz-Borunda J . PPARs as Metabolic Sensors and Therapeutic Targets in Liver Diseases. Int J Mol Sci. 2021; 22(15). PMC: 8347792. DOI: 10.3390/ijms22158298. View

20.

Zuniga J, Cancino M, Medina F, Varela P, Vargas R, Tapia G . N-3 PUFA supplementation triggers PPAR-α activation and PPAR-α/NF-κB interaction: anti-inflammatory implications in liver ischemia-reperfusion injury. PLoS One. 2011; 6(12):e28502. PMC: 3234278. DOI: 10.1371/journal.pone.0028502. View