Metabolomics Reveals Gut Microbiota Contribute to PPARα Deficiency-Induced Alcoholic Liver Injury
journal contributionposted on 2023-05-26, 13:08 authored by Ting Zhang, Lijuan Bao, Qi Zhao, Zhanxuan E. Wu, Manyun Dai, Qianru Rao, Fei Li
Incidence 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 α (PPARα) 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 PPARα 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).
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pxd 041465 ).chain fatty acidsavailable via proteomexchangealcoholic liver diseaseactivated receptor αinduced liver injury>- null micetype miceregulating inflammationpresent studyppara peroxisome proliferatornovel approachmortality rateslipid metabolismlipid accumulationhydroxyphenylacetic acidgut microbiotafindings suggestcm ),clostridium_sensu_stricto_1 alcohol feeding