FABP4 deficiency ameliorates alcoholic steatohepatitis in mice via inhibition of p53 signaling pathway.

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • Subject Terms:
      Fatty Acid-Binding Proteins*/genetics ; Fatty Acid-Binding Proteins*/metabolism ; Signal Transduction* ; Tumor Suppressor Protein p53*/metabolism ; Tumor Suppressor Protein p53*/genetics ; Fatty Liver, Alcoholic*/metabolism ; Fatty Liver, Alcoholic*/genetics ; Fatty Liver, Alcoholic*/pathology; Animals ; Mice ; Mice, Knockout ; Humans ; Male ; Disease Models, Animal ; Liver/metabolism ; Liver/pathology ; Mice, Inbred C57BL ; Sirtuin 1/metabolism ; Sirtuin 1/genetics ; Lipid Metabolism
    • Abstract:
      Fatty acid-binding protein 4 (FABP4) plays an essential role in metabolism and inflammation. However, the role of FABP4 in alcoholic steatohepatitis (ASH) remains unclear. This study aimed to investigate the function and underlying mechanisms of FABP4 in the progression of ASH. We first obtained alcoholic hepatitis (AH) datasets from the National Center for Biotechnology Information-Gene Expression Omnibus database and conducted bioinformatics analysis to identify critical genes in the FABP family. We then established ASH models of the wild-type (WT) and Fabp4-deficient (Fabp4 -/- ) mice to investigate the role of FABP4 in ASH. Additionally, we performed transcriptional profiling of mouse liver tissue and analyzed the results using integrative bioinformatics. The FABP4-associated signaling pathway was further verified. FABP4 was upregulated in two AH datasets and was thus identified as a critical biomarker for AH. FABP4 expression was higher in the liver tissues of patients with alcoholic liver disease and ASH mice than in the corresponding control samples. Furthermore, the Fabp4 -/- ASH mice showed reduced hepatic lipid deposition and inflammation compared with the WT ASH mice. Mechanistically, Fabp4 may be involved in regulating the p53 and sirtuin-1 signaling pathways, subsequently affecting lipid metabolism and macrophage polarization in the liver of ASH mice. Our results demonstrate that Fabp4 is involved in the progression of ASH and that Fabp4 deficiency may ameliorate ASH. Therefore, FABP4 may be a potential therapeutic target for ASH treatment.
      (© 2024. The Author(s).)
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    • Grant Information:
      82160120 National Natural Science Foundation of China
    • Contributed Indexing:
      Keywords: Alcoholic steatohepatitis (ASH); Bioinformatics analysis; FABP4; p53
    • Accession Number:
      0 (Fatty Acid-Binding Proteins)
      0 (Tumor Suppressor Protein p53)
      0 (Fabp4 protein, mouse)
      0 (Trp53 protein, mouse)
      EC 3.5.1.- (Sirtuin 1)
    • Publication Date:
      Date Created: 20240910 Date Completed: 20240910 Latest Revision: 20240918
    • Publication Date:
      20240918
    • Accession Number:
      PMC11387727
    • Accession Number:
      10.1038/s41598-024-71311-8
    • Accession Number:
      39256510