Fig. 9

Model depicts the improvement of metabolic features in db/db mice upon XKY treatment. XKY mitigates hyperglycemia, IR, hyperlipidemia, inflammation and hepatic steatosis. Mechanistically, XKY decreases the hepatic cholesterol synthesis by inhibiting Hmgcr, Mvk, Mvd, Idi1, Fdps, Sqle, Lss, Cyp51, Hsd17b1 and Dhcr24 gene expression. In addition, XKY decreases secondary bile acid producing bacteria (Clostridia and Lachnospircaeae) to mainly result in decreasing the levels of proinflammatory factors (IL-6 and TNF-α) and secondary bile acids (lithocholic acid (LCA) and deoxycholic acid (DCA), and maintaining intestinal epithelial homeostasis, and to further promote hepatic bile acid synthesis by inhibiting the LCA/DCA-FXR-FGF15 signaling pathway followed by down-regulating Cyp7a1, Cyp8b1, Cyp27a1 and Cyp7b1 gene expression. Furthermore, XKY regulates amino acid metabolism including arginine biosynthesis, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and tryptophan metabolism likely by increasing Bacilli, Lactobacillaceae and Lactobacillus, and decreasing Clostridia, Lachnospircaeae, Tannerellaceae and Parabacteroides abundances. This figure was created with BioRender.com.