In this study, through a comparison of treatments with different variation of radiation dosage exposures, and combined with a HFD diet, we identified the specific mechanism by which a varying pattern of radiation exposure and a HFD alters the intestinal microbiota, damages the intestinal barrier, and increases LCA levels, thus promoting the development and progression of HFD-induced NAFLD via the activation of liver INSR/PI3K/Akt signaling. Here, AKT1 is linked to metabolic dysfunction-associated steatotic liver disease.