However, this hypothesis is in sharp contrast to the phenotype of PNPLA3-deficient mice, which show no signs of fatty liver disease [169,173], whereas the overexpression of defective PNPLA3 variants (p.Iso148Met or p.Ser47Ala) leads to hepatic steatosis in mice [178,179]. This evidence concerns the gene PNPLA3 and fatty liver disease.