Elafibranor alleviates alcohol-related liver fibrosis by restoring intestinal barrier function

Table 1 Roles of elafibranor and other peroxisome proliferator-activated receptor agonists

Agonists	Roles
PPARα agonists
Bezafibrate	Bezafibrate promotes fatty acid β-oxidation and ketogenesis while reducing abnormal lipid metabolism, inflammation, oxidative stress, and insulin resistance[71]. It ameliorates steatosis, alters lipid composition, and increases mitochondrial mass in the liver[72]
Fenofibrate	Fenofibrate has been shown to improve hepatic steatosis and increase TFEB activation, leading to lower levels of LDL and VLDL. It also elevates HDL levels and decreases TG levels[73]
Ciprofibrate	Ciprofibrate stimulates the expression of the CETP gene and alters cholesterol flow through reverse cholesterol transport, facilitating plasma cholesterol removal via LDL[74]
PPARα/δ agonists
Elafibranor	EFN promotes lipolysis and β-oxidation, enhances autophagy and antioxidant capacity, inhibits Kupffer cell-mediated inflammatory responses, and impairs the LPS and TLR4/NF-κB signaling pathways. Additionally, EFN improves intestinal barrier hyperpermeability by restoring tight junction proteins, enhancing autophagy, and inhibiting both apoptosis and inflammatory responses[37]
PPARγ agonists
Rosiglitazone	Rosiglitazone increases the expression of adipogenic and energetic genes in adipose tissue, as well as defense genes in macrophages[71]. It is primarily used to treat type 2 diabetes, enhancing glucose utilization by cells, which subsequently lowers blood sugar levels[75]
Pioglitazone	Pioglitazone reduces glucose production in the liver, lowers triglyceride levels, and increases HDL, thus improving insulin sensitivity[76]

PPAR: Peroxisome proliferator-activated receptor; LDL: Low-density lipoprotein; VLDL: Very-low-density lipoprotein; HDL: High-density lipoprotein; TG: Triglyceride; CETP: Cholesteryl ester transfer protein; EFN: Elafibranor; LPS: Lipopolysaccharides; TLR4: Toll-like receptor 4; NF-κB: Nuclear factor κB.