Miniatura

Fitxers

Impact of Liver Inflammation on Bile Acid Side Chain_Cells.pdf (3.69 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2022-12-09

Llicència de publicació

cc by (c) Alonso Peña, Marta et al, 2022
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/199557

Impact of Liver Inflammation on Bile Acid Side Chain Shortening and Amidation

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.3390/cells11243983

Resum

Bile acid (BA) synthesis from cholesterol by hepatocytes is inhibited by inflammatory cytokines. Whether liver inflammation also affects BA side chain shortening and conjugation was investigated. In human liver cell lines (IHH, HepG2, and HepaRG), agonists of nuclear receptors including the farnesoid X receptor (FXR), liver X receptor (LXR), and peroxisome proliferator-activated receptors (PPARs) did not affect the expression of BA-related peroxisomal enzymes. In contrast, hepatocyte nuclear factor 4? (HNF4?) inhibition down-regulated acyl-CoA oxidase 2 (ACOX2). ACOX2 was repressed by fibroblast growth factor 19 (FGF19), which was prevented by extracellular signal-regulated kinase (ERK) pathway inhibition. These changes were paralleled by altered BA synthesis (HPLC-MS/MS). Cytokines able to down-regulate cholesterol-7?-hydroxylase (CYP7A1) had little effect on peroxisomal enzymes involved in BA synthesis except for ACOX2 and bile acid-CoA:amino acid N-acyltransferase (BAAT), which were down-regulated, mainly by oncostatin M (OSM). This effect was prevented by Janus kinase (JAK) inhibition, which restored BA side chain shortening and conjugation. The binding of OSM to the extracellular matrix accounted for a persistent effect after culture medium replacement. In silico analysis of four databases (n = 201) and a validation cohort (n = 90) revealed an inverse relationship between liver inflammation and ACOX2/BAAT expression which was associated with changes in HNF4? levels. In conclusion, BA side chain shortening and conjugation are inhibited by inflammatory effectors. However, other mechanisms involved in BA homeostasis counterbalance any significant impact on the serum BA profile.

Matèries

Malalties del fetge, Colesterol

Matèries (anglès)

Liver diseases, Cholesterol

Citació

Col·leccions

Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

ALONSO PEÑA, Marta, ESPINOSA ESCUDERO, Ricardo, HERMANNS, Heike m., BRIZ, Oscar, HERRANZ, José m., GARCÍA RUIZ, Carmen, FERNÁNDEZ CHECA TORRES, José carlos, JUAMPEREZ, Javier, ÁVILA, Matías, ARGEMÍ, Josep maria, BATALLER ALBEROLA, Ramón, CRESPO, Javier, MONTE, María j., GEIER, Andreas, HERRAEZ, Elisa, MARÍN, José j. g.. Impact of Liver Inflammation on Bile Acid Side Chain Shortening and Amidation. _Cells_. 2022. Vol. 11, núm. 24. [consulta: 26 de gener de 2026]. ISSN: 2073-4409. [Disponible a: https://hdl.handle.net/2445/199557]

Exportar metadades

JSON - METS

Compartir registre