Regarding the role of betatrophin in modulating beta cell functions [6], fatty acid metabolism and lipid homeostasis [2,3,4], it would be tempting to consider that elevation of betatrophin levels in the early stages of NAFLD may be a self defense of liver in response to cardiovascular and metabolic offenses such as aging, obesity, dyslipidemia, insulin resistance or glucose intolerance [24,25]. Here, ANGPTL8 is linked to obesity due to melanocortin 4 receptor deficiency.