LPS-related muscle loss is associated with the alteration of Bacteroidetes abundance, systemic inflammation, and mitochondrial morphology in a weaned piglet model.

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      Publisher: Science China Press, co-published with Springer Country of Publication: China NLM ID: 101529880 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1869-1889 (Electronic) Linking ISSN: 16747305 NLM ISO Abbreviation: Sci China Life Sci Subsets: MEDLINE
    • Publication Information:
      Original Publication: Beijing : Science China Press, co-published with Springer
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    • Abstract:
      We previously demonstrated that lipopolysaccharide (LPS) injection-induced immune stress could impair muscle growth in weaned piglets, but the precise mechanisms behind this remain elusive. Here, we found that chronic immune stress induced by LPS resulted in a significant reduction of 36.86% in the total muscle mass of piglets at 5 d post-treatment compared with the control group. At 1 d, prior to muscle mass loss, multiple alterations were noted in response to LPS treatment. These included a reduction in the abundance of Bacteroidetes, an increase in serum concentrations of pro-inflammatory cytokines, compromised mitochondrial morphology, and an upregulation in the expression of dynamin-related protein 1 (Drp1), a critical protein involved in mitochondrial fission. We highlight a strong negative correlation between Bacteroidetes abundance and the levels of serum pro-inflammatory cytokines, corroborated by in vivo intervention strategies in the musculature of both pig and mouse models. Mechanistically, the effects of Bacteroidetes on inflammation and muscle mass loss may involve the signaling pathway of the tauro-β-muricholic acid-fibroblast growth factor 15. Furthermore, the induction of overexpression of inflammatory cytokines, achieved without LPS treatment through oral administration of recombinant human IL-6 (rhIL-6), led to increased levels of circulating cytokines, subsequently causing a decrease in muscle mass. Notably, pre-treatment with Mdivi-1, an inhibitor of Drp-1, markedly attenuated the LPS-induced elevation in reactive oxygen species levels and rescued the associated decline in muscle mass. Collectively, these data indicate that LPS-induced muscle mass loss was linked to the reduction of Bacteroidetes abundance, increased inflammation, and the disruption of mitochondrial morphology. These insights offer promising avenues for the identification of potential therapeutic targets aimed at mitigating muscle mass loss.
      (© 2024. Science China Press.)
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    • Contributed Indexing:
      Keywords: Bacteroidetes; inflammation; mitochondrial morphology; muscle mass loss; piglets
    • Accession Number:
      0 (Lipopolysaccharides)
      0 (Cytokines)
      EC 3.6.5.5 (Dynamins)
      0 (Interleukin-6)
    • Publication Date:
      Date Created: 20240624 Date Completed: 20240827 Latest Revision: 20240827
    • Publication Date:
      20240828
    • Accession Number:
      10.1007/s11427-023-2552-7
    • Accession Number:
      38913237