1-Carbon Cycle Metabolites Methylate Their Way to Fatty Liver

Fatty liver is a complex disease often accompanying metabolic syndrome and Type 2 diabetes mellitus (T2DM). Hepatosteatosis may have roots in multiple metabolic abnormalities. However, metabolic dysfunction in the 1-carbon cycle (1CC), which produces the methyl donor S-adenosylmethionine (SAM) and phosphatidylcholine (PC), induces hepatic lipogenesis in model systems. Human diseases where 1CC or PC synthesis is disrupted, such as alcoholism, congenital lipodystrophy, or cystic fibrosis, often present with fatty liver. Given that the 1CC is clearly linked to this disease, it is critical to understand how the individual metabolites drive mechanisms increasing stored hepatic lipids. In this review, I summarize evidence that ties the 1CC to fatty liver disease along with data proposing mechanisms for increased lipogenesis or decreased lipid export by phosphatidylcholine.