A Perspective on Metabolic Syndrome and Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is increasingly being diagnosed worldwide and is strongly associated with the features of metabolic syndrome. In this brief review, we discuss two key questions relating to NAFLD and metabolic syndrome: (1) Does NAFLD predict the development of type 2 diabetes mellitus and metabolic syndrome, or is it simply an epiphenomenon? (2) Are there differences between metabolic syndrome-associated NAFLD and NAFLD associated with genetic variation in the patatin-like phospholipase domain-containing 3 (PNPLA3) gene? Accumulating evidence indicates that NAFLD is not simply the hepatic manifestation of the metabolic syndrome, but is a pathogenic determinant of the syndrome. Genetic variation within the PNPLA3 gene (e.g., I148M homozygosity) confers a higher risk of developing more severe histological features of NAFLD, but a lower risk of developing metabolic syndrome traits. We suggest that future research is now required to elucidate whether both metabolic syndrome-related NAFLD and PNPLA3-related NAFLD produce the same risk of developing extrahepatic complications.