TNFR1-mediated pathways create a pro-inflammatory microenvironment which not only plays a role for insulin resistance, liver injury, fibrogenesis and thus for NAFLD progression, but also critically contributes to the development of obesity-related hepatocellular carcinoma8,20–22. The gene discussed is TNFRSF1A; the disease is obesity due to melanocortin 4 receptor deficiency.