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• W4366134139 endingPage "159319" @default.
• W4366134139 startingPage "159319" @default.
• W4366134139 abstract "12α-Hydroxylated (12αOH) bile acids (BAs) selectively increase with high-fat diet intake. Dietary supplementation with cholic acid (CA) in rats is a possible strategy to reveal the causal link between 12αOH BAs and hepatic steatosis. The present study aimed to investigate the metabolic mechanism underlying the effect of 12αOH BAs on hepatic steatosis. Male WKAH rats were fed either a control (Ct) or CA-supplemented diet (0.5 g/kg). After the 12-week intervention, the CA diet elevated the 12αOH BA levels in the gut–liver axis. CA-fed rats showed greater hepatic lipid accumulation than in the Ct group, regardless of the dietary energy balance. Untargeted metabolomics suggested marked differences in the fecal metabolome of rats subjected to the CA diet compared with that of Ct, characterized by the depletion of fatty acids and enrichment of amino acids and amines. Moreover, the liver metabolome differed in the CA group, characterized by an alteration in redox-related pathways. The CA diet elevated nicotinamide adenine dinucleotide consumption owing to the activation of poly(ADP-ribose) polymerase 1, resulting in impaired peroxisome proliferator-activated receptor α signaling in the liver. The CA diet increased sedoheptulose 7-phosphate, and enhanced glucose-6-phosphate dehydrogenase activity, suggesting promotion of the pentose phosphate pathway that generates reducing equivalents. Integrated analysis of the gut–liver metabolomic data revealed the role of deoxycholic acid and its liver counterpart in mediating these metabolic alterations. These observations suggest that alterations in metabolites induced by 12αOH BAs in the gut–liver axis contribute to the enhancement of liver lipid accumulation." @default.
• W4366134139 created "2023-04-19" @default.
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• W4366134139 date "2023-07-01" @default.
• W4366134139 modified "2023-10-14" @default.
• W4366134139 title "Metabolic alterations of the gut–liver axis induced by cholic acid contribute to hepatic steatosis in rats" @default.
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• W4366134139 doi "https://doi.org/10.1016/j.bbalip.2023.159319" @default.
• W4366134139 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37075973" @default.
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