INS and obesity due to melanocortin 4 receptor deficiency: It has been recently shown that IRE1α mediates saturated fatty acid-induced activation of the NLRp3 inflammasome in human and mouse macrophages [80] and that macrophage-specific deletion of IRE1α conferred resistance to high-fat diet-induced obesity, thereby linking macrophages to ER stress, metaflammation and insulin sensitivity [81].