The present study performed on colonic tissues from SD and HFD mice (WT and NLRP3−/−) as well as on in vitro coculture of EGCs with IECs, pointed out the following points of novelty: (1) NLRP3 inflammasome represents a regulatory hub linking enteric gliotic processes and intestinal mucosal barrier alterations in obesity; (2) enteric glial NLRP3‐mediated IL‐1β release contributes to the impairment of intestinal mucosal barrier associated with obesity. The gene discussed is IL1B; the disease is obesity due to melanocortin 4 receptor deficiency.