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SHMT2 reduces fatty liver but is necessary for liver inflammation and fibrosis in mice

ABSTRACT: Non-alcoholic fatty liver disease is linked to disrupted serine metabolism. SHMT2 is a liver enzyme that is crucial for liver methylation and overall health. We developed a mouse strain with targeted SHMT2 knockout in hepatocytes and found that the absence of SHMT2 led to increased circulating serine and glycine levels, 1C deficiency, and depleted liver methylation potential. The study reveals the critical role of SHMT2 in maintaining hepatic 1C homeostasis and regulating the progression of non-alcoholic fatty liver disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE248883 | GEO | 2024/02/16

REPOSITORIES: GEO

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Project description:Mardinoglu2014 - Genome-scale metabolic model (HMR version 2.0) - human hepatocytes (iHepatocytes2322) This model is described in the article: Genome-scale metabolic modelling of hepatocytes reveals serine deficiency in patients with non-alcoholic fatty liver disease. Mardinoglu A, Agren R, Kampf C, Asplund A, Uhlen M, Nielsen J. Nat Commun 2014; 5: 3083 Abstract: Several liver disorders result from perturbations in the metabolism of hepatocytes, and their underlying mechanisms can be outlined through the use of genome-scale metabolic models (GEMs). Here we reconstruct a consensus GEM for hepatocytes, which we call iHepatocytes2322, that extends previous models by including an extensive description of lipid metabolism. We build iHepatocytes2322 using Human Metabolic Reaction 2.0 database and proteomics data in Human Protein Atlas, which experimentally validates the incorporated reactions. The reconstruction process enables improved annotation of the proteomics data using the network centric view of iHepatocytes2322. We then use iHepatocytes2322 to analyse transcriptomics data obtained from patients with non-alcoholic fatty liver disease. We show that blood concentrations of chondroitin and heparan sulphates are suitable for diagnosing non-alcoholic steatohepatitis and for the staging of non-alcoholic fatty liver disease. Furthermore, we observe serine deficiency in patients with NASH and identify PSPH, SHMT1 and BCAT1 as potential therapeutic targets for the treatment of non-alcoholic steatohepatitis. This model is hosted on BioModels Database and identified by: MODEL1402200003. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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SHMT2 reduces fatty liver but is necessary for liver inflammation and fibrosis in mice

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