Taken together, these findings highlight that HFD‐NLRP3−/− mice showed a normalization of NLRP3 inflammasome‐related inflammatory parameters, thus corroborating the relevant contribution of NLRP3 inflammasome in the onset and maintenance of enteric inflammation associated with obesity, via IL‐1β release. Here, IL1B is linked to obesity due to melanocortin 4 receptor deficiency.