Investigation of dysregulated lipid metabolism in diabetic mice via targeted metabolomics of bile acids in enterohepatic circulation.

Rationale: The mechanism of lipid metabolism disorder in type 2 diabetes (T2DM) remains unclear. This study aimed to reveal the mechanism underlying dysregulated lipid metabolism in T2DM through bile acid metabolism.

Methods: A db/db mouse model was employed to investigate the alteration of bile acid profiles in T2DM. Ultrahigh-performance liquid chromatography with tandem mass spectrometry was used to quantify the detailed bile acid levels in each compartment of enterohepatic circulation. The pathological change of mouse liver was assessed by liver histology and serum biochemical assays. The expression level of bile acid-related transporters and synthases was measured with Western blot analysis.

Results: The results showed that T2DM can result in severe liver fat accumulation and liver damage. In addition, compared to the control group, in T2DM mice, bile acid synthesis is reduced, while the level of bile acids is increased at the storage sites and the reabsorption sites, but there are subtle gender differences. Further, the ratio of conjugated bile acids in total bile acid in the liver of T2DM mice increased significantly relative to the control group for both female and male mice.

Conclusions: In T2DM, bile acid metabolism is disordered in both male and female mice, which could be the underlying mechanism of dysregulated lipid metabolism in T2DM.