In adipose tissue, AREG expression is markedly upregulated during HFD-induced obesity in wild type mice but is profoundly downregulated in iRhom2-deficient mice, suggesting a possibly leading role of EGFR-dependent cellular processes over TNF in the modulation of metabolic pathways during obesity (77). This evidence concerns the gene RHBDF2 and obesity due to melanocortin 4 receptor deficiency.