Considering the proposed linking function of IL-17 between depression, obesity, and inflammation and that IL-17 signaling was highly enriched in the common DEGs of Negr1-deficient mice, we propose that IL-17 as a crucial component of inter-organ communication and responsible for the affective behavior in Negr1−/− mice. Here, NEGR1 is linked to obesity due to melanocortin 4 receptor deficiency.