Anti-steatotic effects of PPAR-alpha and gamma involve gut-liver axis modulation in high-fat diet-fed mice

Aim: To evaluate the effects of PPAR alpha and PPAR gamma activation (alone or in combination) on the gut -liver axis, emphasizing the integrity of the intestinal barrier and hepatic steatosis in mice fed a high saturated fat diet. Methods: Male C57BL/6J were fed a control diet (C) or a high -fat diet (HF) for ten weeks. Then, a four -week treatment started: HF-alpha (WY14643), HF-gamma (low -dose pioglitazone), and HF-alpha gamma (combination). Results: The HF caused overweight, insulin resistance, impaired gut -liver axis, and marked hepatic steatosis. Treatments reduced body mass, improved glucose homeostasis, and restored the gut microbiota diversity and intestinal barrier gene expression. Treatments also lowered the plasma lipopolysaccharide concentrations and favored beta -oxidation genes, reducing macrophage infiltration and steatosis in the liver. Conclusion: Treatment with PPAR agonists modulated the gut microbiota and rescued the integrity of the intestinal barrier, alleviating hepatic steatosis. These results show that these agonists can contribute to metabolicassociated fatty liver disease treatment.