Furthermore, our results also revealed several common upstream regulators associated with immune regulation and resistance to obesity (IL-4, IL-5, IL-33, CD15, HGF, ANGPT2, VEGFA, and neuropilin 1 [Nrp1]), supporting a critical role of intestinal homeostasis in systemic pathogenesis of obesity (Table S11). Here, ANGPT2 is linked to obesity due to melanocortin 4 receptor deficiency.