ArticleAmino acids2022
The role of SHMT2 in modulating lipid metabolism in hepatocytes via glycine-mediated mTOR activation.
Article in Amino acids, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 25 citations in OpenAlex.
- Effects of Chlorantraniliprole on Oxidative Stress, Enzymatic Biomarkers, and Hepatic Transcriptome inInternational journal of molecular sciences · 2026Article
- Comparative Analysis of Meat Quality in Minxinan Black Rabbit and Hyla Rabbit Using Integrated Transcriptomics and Proteomics.Animals : an open access journal from MDPI · 2025Article
- Multifaceted role of serine hydroxymethyltransferase in health and disease.Molecules and cells · 2025Review
- SHMT2 modulates the transcriptome and metabolism profiles to promote the tumor phenotypes of bladder cancer HT-1376 cells.Frontiers in genetics · 2025Article
- Disturbed intracellular folate homeostasis impairs autophagic flux and increases hepatocytic lipid accumulation.BMC biology · 2024Article
- Investigating the Impact of Pineapple-Whey Protein Fermentation Products on Cefixime-Induced Intestinal Flora Dysbiosis in Mice Using 16S Sequencing and Untargeted Metabolomics Techniques.Foods (Basel, Switzerland) · 2024Article
- Metabolic disturbance and transcriptomic changes induced by methyl triclosan in human hepatocyte L02 cells.Toxicology research · 2023Article
- Targeting serine-glycine-one-carbon metabolism as a vulnerability in cancers.Biomarker research · 2023Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Serine hydroxymethyltransferase 2 (SHMT2) converts serine into glycine in the mitochondrial matrix, transferring a methyl group to tetrahydrofolate. SHMT2 plays an important role in the maintenance of one-carbon metabolism. Previously, we found a negative correlation between the serine concentration and the progression of fatty liver disease (FLD). However, little is known about the role of SHMT2 in hepatic lipid metabolism. We established SHMT2 knockdown (KD) mouse primary hepatocytes using RNA interference to investigate the role of SHMT2 in lipid metabolism. SHMT2 KD hepatocytes showed decreased lipid accumulation with reduced glycine levels compared to the scramble cells, which was restored upon reintroducing SHMT2. SHMT2 KD hepatocytes showed downregulation of the mTOR/PPARɣ pathway with decreased gene expression related to lipogenesis and fatty acid uptake. Pharmacological activation of mTOR or PPARɣ overexpression blocked the inhibitory effect of SHMT2 KD on lipid accumulation. We also showed that glycine activated mTOR/PPARɣ signaling and identified glycine as a mediator of SHMT2-responsive lipid accumulation in hepatocytes. In conclusion, silencing SHMT2 in hepatocytes ameliorates lipid accumulation via the glycine-mediated mTOR/PPARɣ pathway. Our findings underscore the possibility of SHMT2 as a therapeutic target of FLD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.