In summary, it appears that there is an optimal range of SAMe concentration in the liver that is mainly maintained by the concerted activity of MATI/III and GNMT (SAMe is an allosteric regulator of GNMT activity), and that below or above this range, liver fat accumulates, which eventually may progress to NASH, fibrosis, and hepatocellular carcinoma. Here, GNMT is linked to hepatocellular carcinoma.