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Metabolomic analysis of a mouse model of NASH and correlation with cytokine expression
Author(s) -
McDermott Caitlin,
Eudy Brandon,
Silva Robin
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.lb315
Subject(s) - steatohepatitis , steatosis , fibrosis , metabolic syndrome , fatty liver , population , metabolomics , inflammation , immunology , medicine , cirrhosis , immune system , hepatocellular carcinoma , biology , endocrinology , bioinformatics , disease , diabetes mellitus , environmental health
Non‐alcoholic fatty liver disease (NAFLD) is a prevalent condition that begins with excess lipid accumulation, termed steatosis. NAFLD is one of the hallmarks of metabolic syndrome with a complex etiology, and over time can progress to nonalcoholic steatohepatitis (NASH), characterized by inflammation and fibrosis. There is no biomarker that can be used to detect fibrosis and therefore the condition can go undetected for a long time. In addition, there are no accepted medical treatments for NASH and extreme cases may progress to cirrhosis and hepatocellular carcinoma (HCC). Past work has identified associations between Glycine N‐methyltransferase (GNMT) and both fibrosis and HCC. The GNMT knockout mouse phenotype ties one‐carbon metabolism to hepatic inflammation and immune function. In humans NASH typically occurs in the obese type 2 diabetic population, but GNMT mice are neither overweight, nor insulin resistant. Therefore, we used a high‐fat diet to investigate the impact of diet on fibrosis. We used a metabolomic approach to identify candidate molecules that may be used to identify hepatic fibrosis. We also use Luminex cytokine analysis to identify altered pathways and immune response that correlate to metabolic changes. Intriguingly we find that GNMT mice receiving a high‐fat diet do not gain weight compared to the wild‐type mice. Our metabolomic analysis has identified several important pathways that contribute to the GNMT phenotype that warrant further investigation. We find interesting correlations with several cytokines including VEGF, M‐CSF, GM‐CSF, IFN gamma, IL‐2, IL‐6 and IL‐10. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .