ArticleHepatology (Baltimore, Md.)2013
Excess S-adenosylmethionine reroutes phosphatidylethanolamine towards phosphatidylcholine and triglyceride synthesis.
Article in Hepatology (Baltimore, Md.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 122 citations in OpenAlex.
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- The Methionine-Mitochondria Axis in Cancer: Metabolic Cross-Talk and Therapeutic Vulnerabilities.Current pharmacology reports · 2026Review
- Rewriting the MASLD-associated hepatocellular carcinoma script: Targeting epigenetics and metabolism.International journal of cancer · 2025Review
- Choline attenuates NEFA-induced hepatic steatosis via GNMT regulation in hepatocytes.Stress biology · 2025Article
- Metabolomics Analysis Uncovers Distinct Profiles of Liver Post-Transplant Patients by Immunosuppression Regimen.Metabolites · 2025Article
- Serum and Liver Lipidome Following Empagliflozin Administration for Six Months in a Fast Food Diet Mouse Model.International journal of molecular sciences · 2025Article
- The complex role of glycine N-methyltransferase in metabolism-a review.Molecular biology reports · 2025Review
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- Clustering-Based Identification of BMI-Associated Metabolites with Mechanistic Insights from Network Analysis in Korean Men.Metabolites · 2025Article
- Dysfunctional VLDL metabolism in MASLD.npj metabolic health and disease · 2024Review
- The Role of Phosphatidylethanolamine N-Methyltransferase (International journal of molecular sciences · 2023Article
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- Serum folate associated with nonalcoholic fatty liver disease and advanced hepatic fibrosis.Scientific reports · 2023Article
- PEMT Mediates Hepatitis C Virus-Induced Steatosis, Explains Genotype-Specific Phenotypes and Supports Virus Replication.International journal of molecular sciences · 2023Article
- Impaired Function of Solute Carrier Family 19 Leads to Low Folate Levels and Lipid Droplet Accumulation in Hepatocytes.Biomedicines · 2023Article
- In Vivo Hepatic Triglyceride Secretion Rate in Antisense Oligonucleotide (ASO)-Treated Mice.Methods in molecular biology (Clifton, N.J.) · 2023Article
- One Carbon Metabolism andLivers · 2022Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
unlabelledMethionine adenosyltransferase 1A (MAT1A) and glycine N-methyltransferase (GNMT) are the primary genes involved in hepatic S-adenosylmethionine (SAMe) synthesis and degradation, respectively. Mat1a ablation in mice induces a decrease in hepatic SAMe, activation of lipogenesis, inhibition of triglyceride (TG) release, and steatosis. Gnmt-deficient mice, despite showing a large increase in hepatic SAMe, also develop steatosis. We hypothesized that as an adaptive response to hepatic SAMe accumulation, phosphatidylcholine (PC) synthesis by way of the phosphatidylethanolamine (PE) N-methyltransferase (PEMT) pathway is stimulated in Gnmt(-/-) mice. We also propose that the excess PC thus generated is catabolized, leading to TG synthesis and steatosis by way of diglyceride (DG) generation. We observed that Gnmt(-/-) mice present with normal hepatic lipogenesis and increased TG release. We also observed that the flux from PE to PC is stimulated in the liver of Gnmt(-/-) mice and that this results in a reduction in PE content and a marked increase in DG and TG. Conversely, reduction of hepatic SAMe following the administration of a methionine-deficient diet reverted the flux from PE to PC of Gnmt(-/-) mice to that of wildtype animals and normalized DG and TG content preventing the development of steatosis. Gnmt(-/-) mice with an additional deletion of perilipin2, the predominant lipid droplet protein, maintain high SAMe levels, with a concurrent increased flux from PE to PC, but do not develop liver steatosis.
conclusionThese findings indicate that excess SAMe reroutes PE towards PC and TG synthesis and lipid sequestration.
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