Our data suggest that the intake of IMP by healthy mice promoted the phosphorylation of the AMPK-activated AMPK-ACC1, AMPK-ACC2, and AMPK-ATGL pathways in hepatocytes, causing TGs accumulation in vivo; therefore, elucidating the mechanism of the periodic intake of IMP-induced lipohyperplasia is important to understand the purine nucleotides metabolic disorder relating to TGs metabolic disorder, and to detail the food safety of IMP-Na2. This evidence concerns the gene PNPLA2 and metabolic disease.