Dataset Information

Bile acids and their receptors: modulators and therapeutic targets in liver inflammation.

ABSTRACT: Bile acids participate in the intestinal emulsion, digestion, and absorption of lipids and fat-soluble vitamins. When present in high concentrations, as in cholestatic liver diseases, bile acids can damage cells and cause inflammation. After the discovery of bile acids receptors about two decades ago, bile acids are considered signaling molecules. Besides regulating bile acid, xenobiotic, and nutrient metabolism, bile acids and their receptors have shown immunomodulatory properties and have been proposed as therapeutic targets for inflammatory diseases of the liver. This review focuses on bile acid-related signaling pathways that affect inflammation in the liver and provides an overview of the preclinical and clinical applications of modulators of these pathways for the treatment of cholestatic and autoimmune liver diseases.

SUBMITTER: Bertolini A

PROVIDER: S-EPMC9256560 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Bile acids and their receptors: modulators and therapeutic targets in liver inflammation.

Bertolini Anna A Fiorotto Romina R Strazzabosco Mario M

Seminars in immunopathology 20220412 4

Bile acids participate in the intestinal emulsion, digestion, and absorption of lipids and fat-soluble vitamins. When present in high concentrations, as in cholestatic liver diseases, bile acids can damage cells and cause inflammation. After the discovery of bile acids receptors about two decades ago, bile acids are considered signaling molecules. Besides regulating bile acid, xenobiotic, and nutrient metabolism, bile acids and their receptors have shown immunomodulatory properties and have been ...[more]

PMID: 35415765

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Project description:ObjectiveTo investigate the changes in bile acid (BA) metabolites within the follicular fluid (FF) of patients with diminished ovarian reserve (DOR) and to identify novel diagnostic markers that could facilitate early detection and intervention in DOR patients.DesignA total of 182 patients undergoing assisted reproductive technology (ART) were enrolled and categorized into the normal ovarian reserve (NOR) group (n = 91) or the DOR group (n = 91) to measure BA levels in FF. To identify the changes in granulosa cells (GCs), we collected GCs from an additional 7 groups of patients for transcriptome sequencing.SettingReproductive medicine center within a hospital and university research laboratory.PopulationA total of 182 patients undergoing assisted reproductive technology were enrolled and categorized into the NOR group (n = 91) or the DOR group (n = 91).MethodsIn this study, BA metabolites in FF of DOR and NOR patients were analyzed in detail by targeted metabolomics, and the correlation between BA levels in FF and clinical indicators was discussed. Then, we constructed a diagnostic model for DOR using the random forest algorithm based on five different BAs. Additionally, we performed a functional enrichment analysis on differentially expressed genes (DEGs) in GCs from both DOR and NOR patients.Main outcome measuresBA levels in FF and their correlation with clinical indicators; the areas under the curve (AUCs) of the random forest diagnostic model for DOR; and the DEGs and corresponding functional enrichment results of GC RNA analysis.Result (s)The levels of lithocholic acid, chenodeoxycholic acid, ursodeoxycholic acid, deoxycholic acid and cholic acid in FF of DOR group were lower than those of NOR group. And significant reductions in total, primary, secondary, and unconjugated BA levels were observed in the DOR group. The above five BAs levels were closely related to indicators of ovarian reserve. The AUC of the diagnostic model based on the above five BAs was 0.964. Based on transcriptome sequencing data from two groups of GCs, a total of 482 up-regulated and 654 down-regulated DEGs were identified. Gene ontology analysis revealed that the metabolic and biosynthetic processes of fatty acids, steroids, and cholesterol were enriched in these DEGs, whereas Kyoto Encyclopedia of Genes and Genomes analysis indicated enrichment of fatty acid and ovarian steroidogenesis.Conclusion(s)The levels of multiple BA metabolites in FF are significantly lower than those in patients with DOR and are closely related to the evaluation of ovarian reserve function.

Dataset Information

Bile acids and their receptors: modulators and therapeutic targets in liver inflammation.

Publications

Bile acids and their receptors: modulators and therapeutic targets in liver inflammation.

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