Intriguingly, despite clear evidence that NLRP3 inflammasome and IL-1β activity drive obesity and MAFLD (Stienstra et al, 2010, 2011; Vandanmagsar et al, 2011; Coll et al, 2022), whether pyroptosis or other modes of programmed cell death, such as apoptosis and necroptosis, facilitate the demise of key cell types in tissues remains ambiguous. This evidence concerns the gene NLRP3 and obesity due to melanocortin 4 receptor deficiency.