%0 Journal Article
%T FXR Antagonist FLG249 Lowers Hepatic Triacylglycerol and Serum Cholesterol Level in High-Fat Diet-Induced Obese Mice.
%A Iguchi Y
%A Yamashita Y
%A Gohda K
%A Oda K
%A Fujimori K
%A Sera Y
%A Imanaka T
%A Yamaguchi M
%A Une M
%A Teno N
%J Biol Pharm Bull
%V 47
%N 8
%D 2024
%M 39135238
%F 2.264
%R 10.1248/bpb.b24-00311
%X Farnesoid X receptor (FXR) is a nuclear receptor that regulates the synthesis and enterohepatic circulation of bile acids (BAs). It also regulates lipid and carbohydrate metabolism, making FXR ligands potential therapeutic agents for systemic and/or hepatic metabolic disorders. We previously synthesized a series of FXR antagonists and showed that oral administration of FLG249 reduced the expression of several FXR target genes in the mouse ileum. Here, we investigated the effects of FLG249 on lipid metabolism in mice fed a high-fat diet (HFD). When FLG249 was administered for 4 weeks to HFD-induced obese mice, it altered the expression of genes related to BA metabolism, ceramide synthesis and fatty acid β-oxidation, improving lipid metabolism in the liver and ileum without decreasing body weight. These findings suggest that FLG249 has the potential to be a low toxicity pharmaceutical compound and likely acts as a nonsteroidal FXR antagonist to improve lipid metabolism disorders.