GSEA analysis revealed that SQE supplementation significantly altered the genes involved in the PPAR signaling pathway such as CYP7A1, CTP1A, CYP27A1, PPARA, FADS1, SCD, RXRA, and PCK1; NOD-like receptor signaling pathway, such as IL8, MAPK3, NOD1, NFKBIB, IL1B, and PIPK2. Since these pathways are relevant to metabolic dysfunctions, such as the insulin resistance and metabolic inflammation induced in the high-fructose-diet-fed rats in this study, we hypothesize that SQE supplementation could alleviate hepatic inflammation and insulin resistance in high-fructose-diet-fed rats. This evidence concerns the gene MAPK3 and Insulin resistance.