Elafibranor is an agonist of the peroxisome proliferator-activated receptors (PPAR) α and δ. It increases HDL secretion and expression of the lipid-related genes ABCA1, PLIN2, and ABHD5 in Caco-2/TC7 cells in a PPARα-dependent manner. Elafibranor (10 mg/kg) decreases levels of plasma triglycerides and total cholesterol while increasing plasma HDL and expression of Acox1, a PPARα target gene, in the liver of ApoE2-KI wild-type, but not PPARα knockout, mice fed a Western diet. However, PPARα knockout mice exhibit a decrease in plasma total and non-HDL cholesterol levels, indicating PPARδ has a role in these functions. Elafibranor (30 mg/kg) reduces diet-induced macro- and micro-steatosis in a PPARα-deficient mouse model of non-alcoholic steatohepatitis. It also reduces cholesterol and triglyceride accumulation as well as macrovesicular steatosis in the liver of insulin-resistant db/db mice fed the methionine-choline deficient (MCD) diet. Formulations containing elafibranor are under clinical investigation for the treatment of non-alcoholic steatohepatitis.
