Taken together, the data indicated that WSHFD-induced obesity caused active lipid metabolites and the S1P mediated ALOX15 signaling could be the potential mechanism for macrophage polarization towards M2 phenotype and TMAs, while recruitment of myeloid cells might play a key role contributing to immunosuppression. This evidence concerns the gene ALOX15 and obesity due to melanocortin 4 receptor deficiency.