In this study, we generated AMPK transgenic mice with a specific KO of AMPK in intestinal epithelial cells and further examined the role of AMPK in metabolic alterations, epigenetic modifications, and colorectal tumorigenesis using an azoxymethane (AOM)/dextran sulfate sodium (DSS) induced-CRC mouse model, as well as in human colonic epithelial Caco-2 cells with AMPK deficiency. The gene discussed is PRKAA1; the disease is colorectal carcinoma.