Elafibranor, also known as GFT505, is a dual agonist of peroxisome proliferator-activated receptor-α/δ (PPAR-α/δ) with EC50 values of 45 and 175nM, respectively[3]. Treatment of hApoE2 KI mice with Elafibranor (30 mg/kg/day) for 6 weeks significantly decreased the plasma concentrations of total cholesterol, triglycerides, and free fatty acids, and greatly increased the level of high-density lipoprotein cholesterol compared to vehicle-treated group. In both hApoE2 KI and hApoE2 KI/PPAR‐α KO mice, Elafibranor treatment significantly reduced hepatic expressions of interleukin‐1β, tumor necrosis factor‐α, transforming growth factor‐β, and tissue inhibitor of metalloproteinase-2. Methionine- and choline-deficient diet induced steatohepatitis in db/db mice, whereas supplementation with Elafibranor (1, 3, or 10 mg/kg/day) for 7 weeks reduced intrahepatic cholesterol and triglyceride content in a dose‐dependent manner. In SD rats concomitantly injected with CCl4 and treated with Elafibranor (30 mg/kg/day) for 7 weeks, the fibrotic surface and hepatic collagen content were significantly decreased, and the number of macrophages and activated hepatic stellate cells were significantly reduced as compared to CCl4 control group[4].
作用机制
Elafibranor is a PPAR-α/δ agonist that exhibits liver-protective effects in non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, and liver fibrosis. It has also been shown to reduce fasting glucose and improve insulin sensitivity similar to PPAR-γ agonist rosiglitazone.
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