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Liver Steatosis and Steatohepatitis Alter Bile Acid Receptors in Brain and Induce Neuroinflammation: A Contribution of Circulating Bile Acids and Blood-Brain Barrier

TitleLiver Steatosis and Steatohepatitis Alter Bile Acid Receptors in Brain and Induce Neuroinflammation: A Contribution of Circulating Bile Acids and Blood-Brain Barrier
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2022
AuthorsFiaschini, N., Mancuso Mariateresa, Tanori Mirella, Colantoni Eleonora, Vitali Roberta, Diretto Gianfranco, L. Rebenaque Lorenzo, Stronati Laura, and Negroni Anna
JournalInternational Journal of Molecular Sciences
Volume23
Issue22
Pagination14254
Date PublishedJan-11-2022
ISSN16616596
Keywordsanimal, Animals, bile acid, Bile Acids and Salts, blood brain barrier, Blood-brain barrier, Brain, Endothelial Cells, endothelium cell, metabolism, Mice, mouse, Neuroinflammatory Diseases, Non-alcoholic Fatty Liver Disease, nonalcoholic fatty liver, occludin
Abstract

A tight relationship between gut-liver diseases and brain functions has recently emerged. Bile acid (BA) receptors, bacterial-derived molecules and the blood-brain barrier (BBB) play key roles in this association. This study was aimed to evaluate how non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) impact the BA receptors Farnesoid X receptor (FXR) and Takeda G-protein coupled receptor 5 (TGR5) expression in the brain and to correlate these effects with circulating BAs composition, BBB integrity and neuroinflammation. A mouse model of NAFLD was set up by a high-fat and sugar diet, and NASH was induced with the supplementation of dextran-sulfate-sodium (DSS) in drinking water. FXR, TGR5 and ionized calcium-binding adaptor molecule 1 (Iba-1) expression in the brain was detected by immunohistochemistry, while Zonula occludens (ZO)-1, Occludin and Plasmalemmal Vesicle Associated Protein-1 (PV-1) were analyzed by immunofluorescence. Biochemical analyses investigated serum BA composition, lipopolysaccharide-binding protein (LBP) and S100β protein (S100β) levels. Results showed a down-regulation of FXR in NASH and an up-regulation of TGR5 and Iba-1 in the cortex and hippocampus in both treated groups as compared to the control group. The BA composition was altered in the serum of both treated groups, and LBP and S100β were significantly augmented in NASH. ZO-1 and Occludin were attenuated in the brain capillary endothelial cells of both treated groups versus the control group. We demonstrated that NAFLD and NASH provoke different grades of brain dysfunction, which are characterized by the altered expression of BA receptors, FXR and TGR5, and activation of microglia. These effects are somewhat promoted by a modification of circulating BAs composition and by an increase in LBP that concur to damage BBB, thus favoring neuroinflammation. © 2022 by the authors.

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URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85142806093&doi=10.3390%2fijms232214254&partnerID=40&md5=a9987684c21b39de073eee01e88f1228
DOI10.3390/ijms232214254
Short TitleIJMS
Citation KeyFiaschini2022