Prue M. Pereira-Fantini, Susan Lapthorne, Cormac G.M. Gahan, Susan A. Joyce, Jenny Charles, Peter J. Fuller, Julie E. Bines
Abstract
Options for the prevention of short-bowel syndrome-associated liver disease (SBS-ALDs) are limited and often ineffective. The farnesoid X receptor (FXR) is a newly emerging pharmaceutical target and FXR agonists have been shown to ameliorate cholestasis and metabolic disorders. The aim of this study was to assess the efficacy of obeticholic acid (OCA) treatment in preventing SBS-ALDs.
Piglets underwent 75% small-bowel resection (SBS) or sham surgery (sham) and were assigned to either a daily dose of OCA (2.4 mg/kg/day) or were untreated. Clinical measures included weight gain and stool studies. Histologic features were assessed. Ultraperformance liquid chromatography tandem mass spectrometry was used to determine bile acid composition in end point bile and portal serum samples. Gene expression of key FXR targets was assessed in intestinal and hepatic tissues via quantitative polymerase chain reaction.
OCA-treated SBS piglets showed decreased stool fat and altered liver histology when compared with nontreated SBS piglets. OCA prevented SBS-associated taurine depletion, however, further analysis of bile and portal serum samples indicated that OCA did not prevent SBS-associated alterations in bile acid composition. The expression of FXR target genes involved in bile acid transport and synthesis increased within the liver of SBS piglets after OCA administration whereas, paradoxically, intestinal expression of FXR target genes were decreased by OCA administration.
Administration of OCA in SBS reduced fat malabsorption and altered bile acid composition, but did not prevent the development of SBS-ALDs. We postulate that extensive small resection impacts the ability of the remnant intestine to respond to FXR activation.
Pharmacology, Toxicology and Pharmaceutical Science
1
3%
Other
4
13%
Unknown
14
44%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 16. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 August 2017.
All research outputs
#2,237,116
of 25,382,440 outputs
Outputs from Cellular and Molecular Gastroenterology and Hepatology
#138
of 1,143 outputs
Outputs of similar age
#41,719
of 324,513 outputs
Outputs of similar age from Cellular and Molecular Gastroenterology and Hepatology
#5
of 29 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 91st percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,143 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.3. This one has done well, scoring higher than 87% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 324,513 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 87% of its contemporaries.
We're also able to compare this research output to 29 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 82% of its contemporaries.
