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Obeticholic acid improves fetal bile acid profile in a mouse model of gestational hypercholanemia.

Artikel i vetenskaplig tidskrift
Författare Vanessa Pataia
Saraid McIlvride
Georgia Papacleovoulou
Caroline Ovadia
Julie A K McDonald
Annika Wahlström
Eugene Jansen
Luciano Adorini
David Shapiro
Julian R Marchesi
Hanns-Ulrich Marschall
Catherine Williamson
Publicerad i American journal of physiology. Gastrointestinal and liver physiology
Volym 319
Nummer/häfte 2
Sidor G197-G211
ISSN 1522-1547
Publiceringsår 2020
Publicerad vid Wallenberglaboratoriet
Institutionen för medicin, avdelningen för molekylär och klinisk medicin
Sidor G197-G211
Språk en
Länkar dx.doi.org/10.1152/ajpgi.00126.2020
www.ncbi.nlm.nih.gov/entrez/query.f...
Ämneskategorier Gastroenterologi, Obstetrik och gynekologi

Sammanfattning

Intrahepatic cholestasis of pregnancy (ICP) is characterized by elevated maternal circulating bile acid levels and associated dyslipidemia. ICP leads to accumulation of bile acids in the fetal compartment and the elevated bile acid concentrations are associated with an increased risk of adverse fetal outcomes. The farnesoid X receptor agonist, obeticholic acid (OCA) is efficient in the treatment of cholestatic conditions such as primary biliary cholangitis. We hypothesized that OCA administration during hypercholanemic pregnancy will improve maternal and fetal bile acid and lipid profiles. Female C57BL/6J mice were fed either: a normal chow diet, a 0.5% cholic acid (CA)-supplemented diet, a 0.03% OCA-supplemented diet, or a 0.5% CA + 0.03% OCA-supplemented diet for 1 week prior to mating and throughout pregnancy until euthanization on day 18. The effects of CA and OCA feeding on maternal and fetal morphometry, bile acid and lipid levels, and cecal microbiota were investigated. OCA administration during gestation did not alter the maternal or fetal body weight or organ morphometry. OCA treatment during hypercholanemic pregnancy reduced bile acid levels in the fetal compartment. However, fetal dyslipidemia was not reversed, and OCA did not impact maternal bile acid levels or dyslipidemia. In conclusion, OCA administration during gestation had no apparent detrimental impact on maternal or fetal morphometry and improved fetal hypercholanemia. As high serum bile acid concentrations in ICP are associated with increased rates of adverse fetal outcomes, further investigations into the potential use of OCA during cholestatic gestation are warranted.

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