Interestingly, this detrimental effect was abrogated upon the incubation of IEC‐6 cells with the IL‐1β receptor antagonist anakinra as well as with conditioned medium derived from silenced‐NLRP3 glial cells, thus confirming the contribution of enteric glial NLRP3‐mediated IL‐1β in the mucosal barrier dysfunctions associated with obesity. Here, NLRP3 is linked to obesity due to melanocortin 4 receptor deficiency.