Influence of ursodeoxycholic acid on hepatic lipid deposition, blood glucose, and insulin levels in high-fat -fed Sprague–Dawley rats

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming a growing public health concern. MASLD often coexists with abnormal glucose metabolism. Currently, there is no standard treatment for MASLD. Aim: To elucidate the influence of ursodeoxycholic acid (UDCA) on hepatic lipid deposition, blood glucose, and insulin levels in high-fat diet-induced Sprague–Dawley (SD) rats. Methods: SD rats were randomly assigned to three groups: Group A, which comprised a normal-diet control group; Group B, which comprised a high-fat-fed group; and Group C, which comprised rats treated with UDCA combined with a high-fat diet. At the end of week 4, we performed oral glucose tolerance tests, measured liver enzymes, triglyceride (TG) and total cholesterol (TC) contents, identified morphological changes of the liver, and quantified the expression of major genes in fatty acid, glucose, and bile acid metabolic pathways using real-time polymerase chain reaction. Results: In comparison to Group A, Group B had higher postprandial glucose, insulin, C-peptide, and hepatic TG and TC concentrations (all p < 0.05); metabolism-related genes were differentially expressed in Group B. In comparison to Group B, the values of these indices were all decreased in Group C (all p < 0.05); UDCA reversed the mRNA expression of metabolism-related genes in Group C (all p < 0.05). Conclusion: UDCA administration decreased hepatic lipid content, blood glucose, and insulin levels in SD rats. Relevance for patients: UDCA may be helpful in the treatment of MASLD and its related comorbidities in clinical practice.