The main findings can be summarized as follows: (1) WD consumption exacerbated AOM/DSS-induced CAC via inflammation, especially the activation of STAT3 and NF-κB in mice; (2) treatment with orlistat notably reduced the lethality rate and the formation of tumors in a WD-driven CAC mouse model; and (3) treatment with orlistat suppressed the aggressiveness of the cancer via the inhibition of STAT3, NF-κB, STAT3, and NF-κB-related gene expression. The gene discussed is STAT3; the disease is infectious otitis media.