It is well established that pro-inflammatory cytokine TNF and anti-inflammatory cytokine IL-10 are critical in regulating the insulin sensitivity and obesity (Chawla et al., 2011; Olefsky and Glass, 2010), so we first detected TNF and IL-10 levels in the serum of WT and TKO mice and found increased TNF and decreased IL-10 proteins in TKO mice relative to WT animals (Figure 2—figure supplement 1A and B). Here, IL10 is linked to obesity due to melanocortin 4 receptor deficiency.