Evidence in obesity and type‐2 diabetes suggests a role for a metabolic inflammasome (“metaflammasome”) in mediating chronic inflammation in peripheral organs implicating IKKβ (inhibitor of nuclear factor kappa‐B kinase subunit beta), IRS1 (insulin receptor substrate 1), JNK (c‐jun N‐terminal kinase), and PKR (double‐stranded RNA protein kinase). Here, IRS1 is linked to obesity due to melanocortin 4 receptor deficiency.