In summary, we determined that variation of radiation dosage of radiation exposure altered the HFD-fed gut microbiota composition in mice through the regulation of gut barrier tight junction-related protein expression, leading to lower IA levels and increased LCA levels, and eventually the inhibition of the liver insulin INSR/PI3K/Akt pathway, thus promoting NAFLD development and progression. The gene discussed is INS; the disease is metabolic dysfunction-associated steatotic liver disease.