Dual GIP and GLP-1 receptor agonist tirzepatide alleviates hepatic steatosis and modulates gut microbiota and bile acid metabolism in diabetic mice

Tirzepatide reduced body weight and improved insulin resistance in diabetic mice.

• The treatment decreased serum and hepatic lipid levels and mitigated liver injury.
• Compared to semaglutide, tirzepatide showed greater effectiveness in reducing hepatic lipid accumulation.
• Tirzepatide improved gut microbiota dysbiosis and bile acid metabolism in diabetic mice.
• The treatment increased the abundance of beneficial gut bacteria genera such as Akkermansia.
• Tirzepatide elevated the ratio of certain bile acids that act as antagonists to beneficial receptors, while reducing their agonist counterparts.
• There was a reduction in the expression of a specific receptor in intestinal tissues associated with bile acid regulation.

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