Publication Date
12-13-2023
Journal
Biomedicines
DOI
10.3390/biomedicines11123303
PMID
38137523
PMCID
PMC10740974
PubMedCentral® Posted Date
12-13-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
transcriptomics, liver, Iberian pig, metabolomics
Abstract
The objective of this study was to investigate whether the impairment of farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling in juvenile pigs with non-alcoholic fatty liver disease (NAFLD) is associated with changes in the composition of the enterohepatic bile acid pool. Eighteen 15-day-old Iberian pigs, pair-housed in pens, were allocated to receive either a control (CON) or high-fructose, high-fat (HFF) diet. Animals were euthanized in week 10, and liver, blood, and distal ileum (DI) samples were collected. HFF-fed pigs developed NAFLD and had decreased FGF19 expression in the DI and lower FGF19 levels in the blood. Compared with the CON, the HFF diet increased the total cholic acid (CA) and the CA to chenodeoxycholic acid (CDCA) ratio in the liver, DI, and blood. CA and CDCA levels in the DI were negatively and positively correlated with ileal FGF19 expression, respectively, and blood levels of FGF19 decreased with an increasing ileal CA to CDCA ratio. Compared with the CON, the HFF diet increased the gene expression of hepatic 12-alpha-hydrolase, which catalyzes the synthesis of CA in the liver. Since CA species are weaker FXR ligands than CDCA, our results suggest that impairment of FXR-FGF19 signaling in NAFLD pigs is associated with a decrease in FXR agonism in the bile acid pool.
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Digestive System Diseases Commons, Gastroenterology Commons, Hepatology Commons, Medical Sciences Commons, Pediatrics Commons