Sodium butyrate alleviates free fatty acid-induced steatosis in primary chicken hepatocytes via the AMPK/PPARα pathway.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: England NLM ID: 0401150 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-3171 (Electronic) Linking ISSN: 00325791 NLM ISO Abbreviation: Poult Sci Subsets: MEDLINE
    • Publication Information:
      Publication: 2020- : [Cambridge, UK] : Elsevier
      Original Publication: Champaign Il : Poultry Science Association
    • Subject Terms:
      PPAR alpha*/genetics ; PPAR alpha*/metabolism ; PPAR alpha*/pharmacology ; Fatty Liver*/chemically induced ; Fatty Liver*/drug therapy ; Fatty Liver*/veterinary ; Abnormalities, Multiple* ; Growth Disorders* ; Heart Septal Defects, Ventricular* ; Craniofacial Abnormalities*; Animals ; Female ; Chickens/genetics ; Fatty Acids, Nonesterified/metabolism ; AMP-Activated Protein Kinases/metabolism ; Butyric Acid/pharmacology ; Butyric Acid/metabolism ; Liver/metabolism ; Hepatocytes ; Lipid Metabolism ; RNA, Messenger/metabolism ; Fatty Acids/metabolism
    • Abstract:
      Fatty liver hemorrhagic syndrome (FLHS) is a prevalent metabolic disorder observed in egg-laying hens, characterized by fatty deposits and cellular steatosis in the liver. Our preliminary investigations have revealed a marked decrease in the concentration of butyric acid in the FLHS strain of laying hens. It has been established that sodium butyrate (NaB) protects against metabolic disorders. However, the underlying mechanism by which butyrate modulates hepato-lipid metabolism to a great extent remains unexplored. In this study, we constructed an isolated in vitro model of chicken primary hepatocytes to induce hepatic steatosis by free fatty acids (FFA). Our results demonstrate that treatment with NaB effectively mitigated FFA-induced hepatic steatosis in chicken hepatocytes by inhibiting lipid accumulation, downregulating the mRNA expression of lipo-synthesis-related genes (sterol regulatory element binding transcription factor 1 (SREBF1), acetyl-CoA carboxylase 1(ACC1), fatty acid synthase (FASN), stearoyl-CoA desaturase 1 (SCD1), liver X receptor α (LXRα), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR)) (P < 0.05), and upregulating the mRNA and protein expression of AMP-activated protein kinase α1 (AMPKα1), peroxisome proliferator-activated receptor α (PPARα), and carnitine palmitoyl-transferase 1A (CPT1A) (P < 0.05). Moreover, AMPK and PPARα inhibitors (Compound C (Comp C) and GW6471, respectively) reversed the protective effects of NaB against FFA-induced hepatic steatosis by blocking the AMPK/PPARα pathway, leading to lipid droplet accumulation and triglyceride (TG) contents in chicken primary hepatocytes. With these findings, NaB can alleviate hepatocyte lipoatrophy injury by activating the AMPK/PPARα pathway, promoting fatty acid oxidation, and reducing lipid synthesis in chicken hepatocytes, potentially being able to provide new ideas for the treatment of FLHS.
      (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: free fatty acid; primary chicken hepatocyte; sodium butyrate; steatosis
    • Accession Number:
      0 (PPAR alpha)
      0 (Fatty Acids, Nonesterified)
      EC 2.7.11.31 (AMP-Activated Protein Kinases)
      107-92-6 (Butyric Acid)
      0 (RNA, Messenger)
      0 (Fatty Acids)
    • Subject Terms:
      Floating-harbor syndrome
    • Publication Date:
      Date Created: 20240222 Date Completed: 20240322 Latest Revision: 20240322
    • Publication Date:
      20240322
    • Accession Number:
      PMC10899032
    • Accession Number:
      10.1016/j.psj.2024.103482
    • Accession Number:
      38387286