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Metabolomics Reveals Gut Microbiota Contribute to PPAR & alpha; Deficiency-Induced Alcoholic Liver Injury
Zhang,Ting; Bao,Lijuan; Zhao,Qi; Wu,Zhanxuan E. E.; Dai,Manyun; Rao,Qianru; Li,Fei
2023
Source PublicationJOURNAL OF PROTEOME RESEARCH
ISSN1535-3907
AbstractIncidence and mortality rates of alcoholic liver disease (ALD) is one of the highest in the world. In the present study, we found that the genetic knockout nuclear receptor the peroxisome proliferator-activated receptor a (PPARa) exacerbated ALD. Lipidomics of the liver revealed changed levels of lipid species encompassing phospholipids, ceramides (CM), and long-chain fatty acids in Ppara-null mice induced by ethanol. Moreover, 4-hydroxyphenylacetic acid (4-HPA) was changed as induced by ethanol in the metabolome of urine. Moreover, the phylum level analysis showed a decrease in the level of Bacteroidetes and an increase in the level of Firmicutes after alcohol feeding in Ppara-null mice, while there was no change in wild-type mice. In Ppara-null mice, the level of Clostridium_sensu_stricto_1 and Romboutsia were upregulated after alcohol feeding. These data revealed that PPARa deficiency potentiated alcohol-induced liver injury through promotion of lipid accumulation, changing the metabolome of urine, and increasing the level of Clostridium_sensu_stricto_1 and Romboutsia. 4-HPA could improve ALD in mice by regulating inflammation and lipid metabolism. Therefore, our findings suggest a novel approach to the treatment of ALD: focusing on the gut microbiota and its metabolites. Data are available via ProteomeXchange (PXD 041465).
Keywordmetabolomics alcohol-induced liver injury gut microbiota PPAR & alpha AROMATIC-AMINO-ACIDS LIPID-METABOLISM FED MICE MODULATION DISEASE AXIS OLEOYLETHANOLAMIDE AGONIST OBESITY DEATH
Subject AreaBiochemistry & Molecular Biology
DOI10.1021/acs.jproteome.3c00093
Indexed BySCI
WOS IDWOS:001015268200001
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Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/75289
Collection中国科学院昆明植物研究所
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Zhang,Ting,Bao,Lijuan,Zhao,Qi,et al. Metabolomics Reveals Gut Microbiota Contribute to PPAR & alpha; Deficiency-Induced Alcoholic Liver Injury[J]. JOURNAL OF PROTEOME RESEARCH,2023.
APA Zhang,Ting.,Bao,Lijuan.,Zhao,Qi.,Wu,Zhanxuan E. E..,Dai,Manyun.,...&Li,Fei.(2023).Metabolomics Reveals Gut Microbiota Contribute to PPAR & alpha; Deficiency-Induced Alcoholic Liver Injury.JOURNAL OF PROTEOME RESEARCH.
MLA Zhang,Ting,et al."Metabolomics Reveals Gut Microbiota Contribute to PPAR & alpha; Deficiency-Induced Alcoholic Liver Injury".JOURNAL OF PROTEOME RESEARCH (2023).
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