Finally, it may also need to concern that obesity and related chronic metabolic inflammation link intimately to unfolded protein response (UPR) and interfere with endoplasmic reticulum (ER) homeostasis, where the non-conventional splicing process of the X-box–binding protein 1 (XBP1) mRNA mediated by the ER sensor-inositol requiring enzyme 1α (IRE1α) is disrupted [110]. This evidence concerns the gene ERN1 and obesity due to melanocortin 4 receptor deficiency.