One study showed that ER stress inositol-requiring enzyme 1α (IRE1α) inhibited the polarization of a macrophage into M2 and then impaired energy expenditure in obesity [41], and the knockdown of CHOP in adipocytes was found to increase the polarization of a macrophage into M2 [42]. This evidence concerns the gene ERN1 and obesity due to melanocortin 4 receptor deficiency.