ArticleDigestive diseases and sciences2013
Dysregulated bile acid synthesis, metabolism and excretion in a high fat-cholesterol diet-induced fibrotic steatohepatitis in rats.
Article in Digestive diseases and sciences, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 37 citations in OpenAlex.
- Article
- Article
- Bile acid metabolism and hepatocellular carcinoma: mechanisms of drug resistance and intervention strategies.Precision clinical medicine · 2025Review
- Effects of therapeutically approved individual bile acids on the development of metabolic dysfunction-associated steatohepatitis a low bile acid mouse model.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Novel Insights into Total Flavonoids ofAntioxidants (Basel, Switzerland) · 2022Article
- Regular exercise combined with ferulic acid exhibits antiobesity effect and regulates metabolic profiles in high-fat diet-induced mice.Frontiers in nutrition · 2022Article
- Mass Spectrometry-Based Metabolomic and Lipidomic Analysis of the Effect of High Fat/High Sugar Diet and GreenshellMetabolites · 2021Article
- One-Pot Extraction and Quantification Method for Bile Acids in the Rat Liver by Capillary Liquid Chromatography Tandem Mass Spectrometry.ACS omega · 2021Article
- Rotavirus Reassortant-Induced Murine Model of Liver Fibrosis Parallels Human Biliary Atresia.Hepatology (Baltimore, Md.) · 2020Article
- High-fat and high-cholesterol diet decreases phosphorylated inositol-requiring kinase-1 and inhibits autophagy process in rat liver.Scientific reports · 2019Article
- Non-alcoholic steatohepatitis aggravates nitric oxide synthase inhibition-induced arteriosclerosis in SHRSP5/Dmcr rat model.International journal of experimental pathology · 2018Article
- Bile acid detoxifying enzymes limit susceptibility to liver fibrosis in female SHRSP5/Dmcr rats fed with a high-fat-cholesterol diet.PloS one · 2018Article
- Article
- Importance of detoxifying enzymes in differentiating fibrotic development between SHRSP5/Dmcr and SHRSP rats.Environmental health and preventive medicine · 2016Article
- Molecular changes in hepatic metabolism and transport in cirrhosis and their functional importance.World journal of gastroenterology · 2016Review
- Altered Bile Acid Metabolome in Patients with Nonalcoholic Steatohepatitis.Digestive diseases and sciences · 2015Article
- Recent insights into farnesoid X receptor in non-alcoholic fatty liver disease.World journal of gastroenterology · 2014Review
- A possible role of chenodeoxycholic acid and glycine-conjugated bile acids in fibrotic steatohepatitis in a dietary rat model.Digestive diseases and sciences · 2014Article
- Pathogenesis of liver cirrhosis.World journal of gastroenterology · 2014Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsCholesterol over-intake is involved in the onset of nonalcoholic steatohepatitis (NASH), and hepatocellular bile acid (BA) accumulation correlates with liver injuries. However, how dietary cholesterol influences cholesterol and BA kinetics in NASH liver remains ambiguous and needs to be clarified.
methodsMolecular markers involved in cholesterol and BA kinetics were investigated at protein and mRNA levels in an already-established stroke-prone spontaneously hypertensive 5/Dmcr rat model with fibrotic steatohepatitis, by feeding a high fat-cholesterol (HFC) diet.
resultsUnlike the control diet, the HFC diet deposited cholesterol greatly in rat livers, where 3-hydroxy-3-methylglutaryl CoA reductase, low-density lipoprotein (LDL) receptor and LDL receptor-related protein-1 were expectedly downregulated, especially at 8 and 14 weeks, suggesting that cholesterol synthesis and uptake in response to cholesterol accumulation may not be disorganized. The HFC diet did not upregulate liver X receptor-α, conversely, it enhanced classic BA synthesis by upregulating cholesterol 7α-hydroxylase but downregulating sterol 12α-hydroxylase, and influenced alternative synthesis by downregulating sterol 27-hydroxylase but upregulating oxysterol 7α-hydroxylase, mainly at 8 and 14 weeks, indicating that there were different productions of primary BA species. Unexpectedly, no feedback inhibition of BA synthesis by farnesoid X receptor occurred. Additionally, the HFC diet impaired BA detoxification by UDP-glucuronosyltransferase and sulfotransferase 2A1, and decreased excretion by bile salt export pump at 8 and 14 weeks, although it induced compensatory export by multidrug resistance-associated protein-3. The disturbed BA detoxification may correlate with suppressed pregnane X receptor and constitutive androstane receptor.
conclusionsThe HFC diet may accumulate BA in rat livers, which influences fibrotic steatohepatitis progression.
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