ArticleJournal of translational medicine2022
Identification of MAP3K4 as a novel regulation factor of hepatic lipid metabolism in non-alcoholic fatty liver disease.
Article in Journal of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed, 12 citations in OpenAlex.
- Identification of potential metabolic biomarkers and immune cell infiltration for metabolic associated steatohepatitis by bioinformatics analysis and machine learning.Scientific reports · 2025Article
- Restoring metabolic flexibility: targeting organelle interaction networks in the pathogenesis and therapy of MASLD.Frontiers in cell and developmental biology · 2025Review
- Deciphering the role of alternative splicing as a potential regulator in fat-tail development of sheep: a comprehensive RNA-seq based study.Scientific reports · 2024Review
- Identification of metabolic biomarkers associated with nonalcoholic fatty liver disease.Lipids in health and disease · 2023Article
- A Multi-Omics Analysis of NASH-Related Prognostic Biomarkers Associated with Drug Sensitivity and Immune Infiltration in Hepatocellular Carcinoma.Journal of clinical medicine · 2023Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNon-alcoholic fatty liver disease (NAFLD) is a metabolic disorder with abnormal lipid metabolism. The present study was to identify regulatory genes related to lipid droplets (LDs) abnormal accumulation in NAFLD.
methodstranscriptomic analysis and bioinformatics analysis (GEO database) were used to identify potential genes in abnormal lipid metabolism of NAFLD. A candidate gene MAP3K4 expression were detected by immunohistochemistry staining in NAFLD and controls. RNA interference and immunoblotting were used to verify the roles of MAP3K4 in the formation of hepatic LDs.
resultsA total of 134 candidate genes were screened, including 44 up-regulated genes and 90 down-regulated genes. 29 genes in the protein-protein interaction (PPI) were selected as hub genes, including MAP3K4. The expression levels of MAP3K4 were positively correlated with NAFLD activity score (r = 0.702, p = 0.002). Furthermore, we found a positive correlation of MAP3K4 expression with serum total cholesterol (r = 0.564, p = 0.023), uric acid levels (r = 0.520, p = 0.039), and body mass index (r = 0.574, p = 0.020). Downregulation of MAP3K4 decreased LDs accumulation in HepG2 cells and reduced the expression of CGI-58 and Plin-2 by imbibition of JNK and group IVA cytosolic phospholipase A2 (cPLA2) activation.
conclusionThe study revealed a number of regulatory genes related to hepatic lipid metabolism of NAFLD, and demonstrated that MAP3K4 played a pivotal role in the hepatic lipogenesis of NAFLD.
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