Through the application of B- and T-cell deficient Rag−/− mice, splenocyte transplantation, and serum exosome transplantation, this study is also the first to elucidate the mechanistic connection between cytokine, miRNA, and hormone in the elafin-mediated regulation of obesity, hyperglycemia, and liver steatosis in HFD-treated mice. This evidence concerns the gene PI3 and obesity due to melanocortin 4 receptor deficiency.