Ebselen improves lipid metabolism by activating PI3K/Akt and inhibiting TLR4/JNK signaling pathway to alleviate nonalcoholic fatty liver.

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  • Additional Information
    • Source:
      Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 9005353 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0023 (Electronic) Linking ISSN: 10434666 NLM ISO Abbreviation: Cytokine Subsets: MEDLINE
    • Publication Information:
      Publication: <2001- > : Oxford : Elsevier Science Ltd.
      Original Publication: [Philadelphia, PA] : Saunders Scientific Publications, W.B. Saunders, [c1989-
    • Subject Terms:
      Non-alcoholic Fatty Liver Disease*/drug therapy ; Non-alcoholic Fatty Liver Disease*/metabolism ; Toll-Like Receptor 4*/metabolism ; Lipid Metabolism*/drug effects ; Proto-Oncogene Proteins c-akt*/metabolism ; Phosphatidylinositol 3-Kinases*/metabolism ; Organoselenium Compounds*/pharmacology ; Organoselenium Compounds*/therapeutic use ; Isoindoles*/pharmacology ; Liver*/metabolism ; Liver*/drug effects ; Mice, Inbred C57BL*; Animals ; Male ; Mice ; Azoles/pharmacology ; Azoles/therapeutic use ; MAP Kinase Signaling System/drug effects ; Diet, High-Fat ; Signal Transduction/drug effects ; Disease Models, Animal
    • Abstract:
      Nonalcoholic fatty liver disease (NAFLD), a metabolic disease associated with obesity and type 2 diabetes. Due to its complex pathogenesis, there are still limitations in the knowledge of the disease. To date, no drug has been approved to treat NAFLD. This study aims to explore the role and mechanism of Ebselen (EbSe) in NAFLD. A high-fat diet-induced mouse model of NAFLD was employed to investigate EbSe function in NAFLD mice by EbSe gavage and to regularly monitor the mouse body weight. HE and oil red O staining were performed, respectively, to detect the pathological damage and lipid accumulation in mouse liver tissues. The biochemical and ELISA kits were employed to measure the levels of ALT, AST, TG, TC, LDL-C, HDL-C and pro-inflammatory cytokines within mouse serum or liver tissue. The expression of key proteins of PPARα, fatty acid β oxidation-related protein, PI3K/Akt and TLR4/JNK signaling pathway was detected by western blot. EbSe significantly downregulated body weight, liver weight and liver lipid accumulation in NAFLD mice and downregulated ALT, AST, TG, TC, LDL-C and increased HDL-C serum levels. EbSe upregulated the expression levels of PPARα and fatty acid β oxidation-associated proteins CPT1α, ACOX1, UCP2 and PGC1α. EbSe promoted Akt and PI3K phosphorylation, and inhibited TLR4 expression and JNK phosphorylation. EbSe can upregulate PPARα to promote fatty acid β-oxidation and improve hepatic lipid metabolism. Meanwhile, EbSe also activated PI3K/Akt and inhibited TLR4/JNK signaling pathway. EbSe is predicted to be an effective therapeutic drug for treating NAFLD.
      Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 Elsevier Ltd. All rights reserved.)
    • Contributed Indexing:
      Keywords: Ebselen; Lipid metabolism; NAFLD; PI3K/Akt; TLR4/JNK
    • Accession Number:
      0 (Toll-Like Receptor 4)
      EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
      EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
      0 (Organoselenium Compounds)
      0 (Isoindoles)
      40X2P7DPGH (ebselen)
      0 (Azoles)
      0 (Tlr4 protein, mouse)
    • Publication Date:
      Date Created: 20240629 Date Completed: 20240725 Latest Revision: 20240725
    • Publication Date:
      20240726
    • Accession Number:
      10.1016/j.cyto.2024.156671
    • Accession Number:
      38943739