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. This evidence concerns the gene NLRP3 and obesity due to melanocortin 4 receptor deficiency.