The Effect of Coenzyme Q10 Supplementation on Bile Acid Metabolism: Insights from Network Pharmacology, Molecular Docking, and Experimental Validation

Scope Bile acids play a crucial role in lipid absorption and the regulation of lipid, glucose, and energy homeostasis. Coenzyme Q10 (CoQ10), a lipophilic antioxidant, has been recognized for its positive effects on obesity and related glycolipid metabolic disorders. However, the relationship between CoQ10 and bile acids has not yet been evaluated. Methods and results This study assesses the impact of CoQ10 treatment on bile acid metabolism in mice on a high‐fat diet using Ultra‐Performance Liquid Chromatography‐tandem Mass Spectrometry. CoQ10 reverses the reduction in serum and colonic total bile acid levels and alters the bile acid profile in mice that are caused by a high‐fat diet. Seventeen potential targets of CoQ10 in bile acid metabolism are identified by network pharmacology, with six being central to the mechanism. Molecular docking shows a high binding affinity of CoQ10 to five of these key targets. Further analyses indicate that farnesoid X (FXR) receptor and Takeda G‐protein coupled receptor 5 (TGR5) may be crucial targets for CoQ10 to regulate bile acid metabolism and exert beneficial effects. Conclusion This study sheds light on the impact of CoQ10 in bile acids metabolism and offers a new perspective on the application of CoQ10 in metabolic health. Coenzyme Q10 (CoQ10) regulates high‐fat diet‐induced bile acid (BA) metabolism in mice, mediated by activation of the FXR pathway and increased levels of BA in the intestine and blood. Intestinal BA activates the TGR5 pathway in intestinal L‐cells and promotes GLP‐1 release. In addition, blood BA activates TGR5 in brown adipose tissue and triggers increased UCP1.