1-Carbon Cycle Metabolites Methylate Their Way to Fatty Liver. (January 2017)

• Record Type: Journal Article
• Authors: Walker, Amy Karol
• Is Part Of: Trends in endocrinology and metabolism. Volume 28:Number 1(2017)
• Page Start: 63
• Page End: 72
• Publication Date: 2017-01
• Subjects: 1-carbon cycle -- methylation -- phosphatidylcholine -- fatty liver; Endocrinology -- Periodicals; Metabolism -- Periodicals; Metabolism; 616.4
• DOI: 10.1016/j.tem.2016.10.004
• Languages: English
• ISSNs: 1043-2760

Abstract

Abstract : 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. Trends: Low levels of 1CC metabolites or the methylated phospholipid PC accompany lipid accumulation in invertebrate models, and rodent and human liver. Levels of SAM, the major methyl donor, and PC have the strongest links as effectors of fatty liver. SAM-dependent DNA or histone methylation could have effects on gene expression. Low PC can affect signaling controlling intracellular transport, activating the lipogenic transcription factor Sterol regulatory element binding protein 1 (SREBP-1). In addition, specific PC isoforms are required for activation of a nuclear hormone receptor (liver-receptor homolog-1, LRH-1) that drives bile acid export from the liver.