Peroxisome Proliferator-Activated Receptors Regulate Hepatic Immunity and Assist in the Treatment of Primary Biliary Cholangitis

Abstract

Fibrates, which are agonists of peroxisome proliferator-activated receptor alpha, have received increasing attention in the treatment of primary biliary cholangitis. Reduced alkaline phosphatase levels and improved clinical outcomes were observed in patients with primary biliary cholangitis with an inadequate response to ursodeoxycholic acid (UDCA) monotherapy4 when treated with bezafibrate or fenofibrate combined with UDCA. In contrast to obeticholic acid, which exacerbates pruritus in patients, fibrates have been shown to relieve pruritus. Clinical trial outcomes show potential for the treatment of primary biliary cholangitis by targeting peroxisome proliferator-activated receptors. It is currently agreed that primary biliary cholangitis is an autoimmune-mediated cholestatic liver disease, and peroxisome proliferator-activated receptor is a nuclear receptor that regulates the functions of multiple immune cells, thus playing an important role in regulating innate and adaptive immunity. Therefore, this review focuses on the immune disorder of primary biliary cholangitis and summarizes the regulation of hepatic immunity when peroxisome proliferator-activated receptors are targeted for treating primary biliary cholangitis.

Effects of kiwi fruit (Actinidia chinensis) polysaccharides on metabolites and gut microbiota of acrylamide-induced mice

“…Chenodeoxycholic, taurocholic, and cholic acids are effective components of bile acids (BAs). In the liver, cholesterol is converted to 7α-hydroxycholesterol by CYP7A1, which is then converted to chenodeoxycholic, taurocholic, and cholic acids by sterol 12α-hydroxylase and CYP27A1 ( 49 ). BAs are closely related to enterohepatic circulation and their serum levels indicate the status of BAs metabolism ( 50 ).…”

Lipoprotein lipids and apolipoproteins in primary immune thrombocytopenia: Results from a clinical characteristics and causal relationship verification, potential drug target identification by Mendelian randomization analyses

“…53 In drug-target MR analysis, ABCA1 was also been identified as a potential druggable protein. Several drugs activating ABCA1 via transcription factors have been investigated to treat autoimmune disease, including peroxisome proliferator-activated receptor alpha (PPARA) agonists 54,55 and liver X receptor (LXR) agonists. 56 Apart from cholesterol efflux in DCs, the HDL particle also acts as a carrier of lipid mediators with immunomodulating effects such as apolipoprotein M-bound sphingosine-1-phosphate, which activates the group of sphingosine-1-phosphate (SIP) receptors, a key regulator of lymphocyte egress.…”

“…In drug‐target MR analysis, ABCA1 was also been identified as a potential druggable protein. Several drugs activating ABCA1 via transcription factors have been investigated to treat autoimmune disease, including peroxisome proliferator‐activated receptor alpha (PPARA) agonists 54,55 and liver X receptor (LXR) agonists 56 …”

Selected Aspects of the Intricate Background of Immune-Related Cholangiopathies—A Critical Overview

“…Fibrates are antilipemic agents that lower cholesterol and triglyceride levels. They act as agonists of peroxisome proliferator-activated receptors, and in combination with UDCA have shown potential benefit in patients with PBC [ 201 , 202 ]. Bezafibrate was first reported as biologically effective in patients with PBC who were refractory to UDCA in 1999 [ 23 ].…”