Vitamin K1 ameliorates lipopolysaccharide‐triggered skeletal muscle damage revealed by faecal bacteria transplantation
Abstract Background Sepsis‐associated muscle weakness is common in patients of intensive care units (ICUs), and it is closely associated with poor outcomes. The mechanism of sepsis‐induced muscle weakness is unclear. Recent studies have found that gut microbiota and metabolites are involved in the r...
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Format: | Article |
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Wiley
2024-02-01
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Series: | Journal of Cachexia, Sarcopenia and Muscle |
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Online Access: | https://doi.org/10.1002/jcsm.13379 |
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author | Yuru Xiao Jianguo Feng Jing Jia Jie Li Yingshun Zhou Zhangyong Song Fasheng Guan Xuexin Li Li Liu |
author_facet | Yuru Xiao Jianguo Feng Jing Jia Jie Li Yingshun Zhou Zhangyong Song Fasheng Guan Xuexin Li Li Liu |
author_sort | Yuru Xiao |
collection | DOAJ |
description | Abstract Background Sepsis‐associated muscle weakness is common in patients of intensive care units (ICUs), and it is closely associated with poor outcomes. The mechanism of sepsis‐induced muscle weakness is unclear. Recent studies have found that gut microbiota and metabolites are involved in the regulation of skeletal muscle mass and metabolism. This study aimed to investigate the effects of gut microbiota and metabolites on sepsis‐associated muscle weakness. Methods In a lipopolysaccharide (LPS)‐induced inflammation mouse model, mice with different sensitivities to LPS‐induced inflammation were considered as donor mice for the faecal microbiota transplantation (FMT) assay, and recipient mice were divided into sensitive (Sen) and resistant (Res) groups. Skeletal muscle mass and function, as well as colonic barrier integrity were tested and gut microbiota and metabolite composition were analysed in both groups of mice. The effect of intestinal differential metabolite vitamin K1 on LPS‐triggered muscle damage was investigated, and the underlying mechanism was explored. Results Recipients exhibited varying LPS‐triggered muscle damage and intestinal barrier disruption. Tibialis anterior (TA) muscle of Sen exhibited upregulated expression levels of MuRF‐1 (0.825 ± 0.063 vs. 0.304 ± 0.293, P = 0.0141) and MAFbx (1.055 ± 0.079 vs. 0.456 ± 0.3, P = 0.0092). Colonic tight junction proteins ZO‐1 (0.550 ± 0.087 vs. 0.842 ± 0.094, P = 0.0492) and occludin (0.284 ± 0.057 vs. 0.664 ± 0.191, P = 0.0487) were significantly downregulated in the Sen group. Metabolomic analysis showed significantly higher vitamin K1 in the faeces (P = 0.0195) and serum of the Res group (P = 0.0079) than those of the Sen group. After vitamin K1 intervention, muscle atrophy‐related protein expression downregulated (P < 0.05). Meanwhile SIRT1 protein expression were upregulated (0.320 ± 0.035 vs. 0.685 ± 0.081, P = 0.0281) and pNF‐κB protein expression were downregulated (0.815 ± 0.295 vs. 0.258 ± 0.130, P = 0.0308). PI3K (0.365 ± 0.142 vs. 0.763 ± 0.013, P = 0.0475), pAKT (0.493 ± 0.159 vs. 1.183 ± 0.344, P = 0.0254) and pmTOR (0.509 ± 0.088 vs. 1.110 ± 0.190, P = 0.0368) protein expression levels were upregulated in TA muscle. Meanwhile, vitamin K1 attenuated serum inflammatory factor levels. Conclusions Vitamin K1 might ameliorate LPS‐triggered skeletal muscle damage by antagonizing NF‐κB‐mediated inflammation through upregulation of SIRT1 and regulating the balance between protein synthesis and catabolism. |
first_indexed | 2024-03-08T08:32:58Z |
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issn | 2190-5991 2190-6009 |
language | English |
last_indexed | 2024-03-08T08:32:58Z |
publishDate | 2024-02-01 |
publisher | Wiley |
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spelling | doaj.art-0e851504774f411bb846f0cb6521fad62024-02-02T02:28:29ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092024-02-01151819710.1002/jcsm.13379Vitamin K1 ameliorates lipopolysaccharide‐triggered skeletal muscle damage revealed by faecal bacteria transplantationYuru Xiao0Jianguo Feng1Jing Jia2Jie Li3Yingshun Zhou4Zhangyong Song5Fasheng Guan6Xuexin Li7Li Liu8Department of Anesthesiology The Affiliated Hospital of Southwest Medical University Luzhou ChinaDepartment of Anesthesiology The Affiliated Hospital of Southwest Medical University Luzhou ChinaDepartment of Anesthesiology The Affiliated Hospital of Southwest Medical University Luzhou ChinaDepartment of Anesthesiology The Affiliated Hospital of Southwest Medical University Luzhou ChinaLaboratory of Pathogen and Microbiology Southwest Medical University Luzhou ChinaDepartment of Pathogenic Biology Southwest Medical University Luzhou ChinaDepartment of Anesthesiology Southwest Medical University Luzhou ChinaDepartment of Anesthesiology Southwest Medical University Luzhou ChinaDepartment of Anesthesiology The Affiliated Hospital of Southwest Medical University Luzhou ChinaAbstract Background Sepsis‐associated muscle weakness is common in patients of intensive care units (ICUs), and it is closely associated with poor outcomes. The mechanism of sepsis‐induced muscle weakness is unclear. Recent studies have found that gut microbiota and metabolites are involved in the regulation of skeletal muscle mass and metabolism. This study aimed to investigate the effects of gut microbiota and metabolites on sepsis‐associated muscle weakness. Methods In a lipopolysaccharide (LPS)‐induced inflammation mouse model, mice with different sensitivities to LPS‐induced inflammation were considered as donor mice for the faecal microbiota transplantation (FMT) assay, and recipient mice were divided into sensitive (Sen) and resistant (Res) groups. Skeletal muscle mass and function, as well as colonic barrier integrity were tested and gut microbiota and metabolite composition were analysed in both groups of mice. The effect of intestinal differential metabolite vitamin K1 on LPS‐triggered muscle damage was investigated, and the underlying mechanism was explored. Results Recipients exhibited varying LPS‐triggered muscle damage and intestinal barrier disruption. Tibialis anterior (TA) muscle of Sen exhibited upregulated expression levels of MuRF‐1 (0.825 ± 0.063 vs. 0.304 ± 0.293, P = 0.0141) and MAFbx (1.055 ± 0.079 vs. 0.456 ± 0.3, P = 0.0092). Colonic tight junction proteins ZO‐1 (0.550 ± 0.087 vs. 0.842 ± 0.094, P = 0.0492) and occludin (0.284 ± 0.057 vs. 0.664 ± 0.191, P = 0.0487) were significantly downregulated in the Sen group. Metabolomic analysis showed significantly higher vitamin K1 in the faeces (P = 0.0195) and serum of the Res group (P = 0.0079) than those of the Sen group. After vitamin K1 intervention, muscle atrophy‐related protein expression downregulated (P < 0.05). Meanwhile SIRT1 protein expression were upregulated (0.320 ± 0.035 vs. 0.685 ± 0.081, P = 0.0281) and pNF‐κB protein expression were downregulated (0.815 ± 0.295 vs. 0.258 ± 0.130, P = 0.0308). PI3K (0.365 ± 0.142 vs. 0.763 ± 0.013, P = 0.0475), pAKT (0.493 ± 0.159 vs. 1.183 ± 0.344, P = 0.0254) and pmTOR (0.509 ± 0.088 vs. 1.110 ± 0.190, P = 0.0368) protein expression levels were upregulated in TA muscle. Meanwhile, vitamin K1 attenuated serum inflammatory factor levels. Conclusions Vitamin K1 might ameliorate LPS‐triggered skeletal muscle damage by antagonizing NF‐κB‐mediated inflammation through upregulation of SIRT1 and regulating the balance between protein synthesis and catabolism.https://doi.org/10.1002/jcsm.13379Gut microbiotaInflammationMuscle weaknessSepsisSIRT1Vitamin K1 |
spellingShingle | Yuru Xiao Jianguo Feng Jing Jia Jie Li Yingshun Zhou Zhangyong Song Fasheng Guan Xuexin Li Li Liu Vitamin K1 ameliorates lipopolysaccharide‐triggered skeletal muscle damage revealed by faecal bacteria transplantation Journal of Cachexia, Sarcopenia and Muscle Gut microbiota Inflammation Muscle weakness Sepsis SIRT1 Vitamin K1 |
title | Vitamin K1 ameliorates lipopolysaccharide‐triggered skeletal muscle damage revealed by faecal bacteria transplantation |
title_full | Vitamin K1 ameliorates lipopolysaccharide‐triggered skeletal muscle damage revealed by faecal bacteria transplantation |
title_fullStr | Vitamin K1 ameliorates lipopolysaccharide‐triggered skeletal muscle damage revealed by faecal bacteria transplantation |
title_full_unstemmed | Vitamin K1 ameliorates lipopolysaccharide‐triggered skeletal muscle damage revealed by faecal bacteria transplantation |
title_short | Vitamin K1 ameliorates lipopolysaccharide‐triggered skeletal muscle damage revealed by faecal bacteria transplantation |
title_sort | vitamin k1 ameliorates lipopolysaccharide triggered skeletal muscle damage revealed by faecal bacteria transplantation |
topic | Gut microbiota Inflammation Muscle weakness Sepsis SIRT1 Vitamin K1 |
url | https://doi.org/10.1002/jcsm.13379 |
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