Digestive Diseases and Sciences

, Volume 59, Issue 7, pp 1490–1501

A Possible Role of Chenodeoxycholic Acid and Glycine-Conjugated Bile Acids in Fibrotic Steatohepatitis in a Dietary Rat Model

  • Xiaofang Jia
  • Yudai Suzuki
  • Hisao Naito
  • Husna Yetti
  • Kazuya Kitamori
  • Yumi Hayashi
  • Rina Kaneko
  • Mina Nomura
  • Yukio Yamori
  • Kei Zaitsu
  • Masashi Kato
  • Akira Ishii
  • Tamie Nakajima
Original Article

DOI: 10.1007/s10620-014-3028-3

Cite this article as:
Jia, X., Suzuki, Y., Naito, H. et al. Dig Dis Sci (2014) 59: 1490. doi:10.1007/s10620-014-3028-3

Abstract

Background and Aims

Our previous study indicated that hepatic bile acids (BAs) may have deposited and stimulated the pathogenesis of a high fat-cholesterol (HFC) diet-induced fibrotic steatohepatitis in stroke-prone spontaneously hypertensive 5/Dmcr rats, based on dysregulated BA homeostasis pathways. We aimed to further characterize BA profiles in liver and evaluate their relationships to liver injury using this model.

Methods

Hepatic 21 BA levels were determined by ultra-performance liquid chromatography-tandem mass spectrometry, and their correlations with macrovesicular steatosis score, serum alanine aminotransferase (ALT) level and quantified fibrotic area were assessed using Spearman and Pearson correlations.

Results

Compared to control, BAs highly accumulated in HFC-fed rat liver at 2 weeks: cholic acid (CA), deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA) were major species, thereafter, levels of CA and DCA declined, but CDCA species persistently increased, which induced a decrease in total CA/total CDCA ratio at 8 and 14 weeks. CDCA species positively, while total CA/total CDCA negatively, correlated with macrovesicular steatosis score, serum ALT and quantified fibrotic area. Unlike control, total ursodeoxycholic acid was minor in HFC-fed rat liver, and inversely correlated to aforementioned indicators of liver injury; total glyco-BAs, rather than tauro-BAs, were predominant in HFC-fed rat liver, and positively correlated with macrovesicular steatosis score. Moreover, its ratio to total tauro-BAs positively correlated with each parameter of liver injury, while inverse associations were detected for total tauro-BAs.

Conclusions

Hepatic BA accumulation may potentiate liver disease. CDCA and glyco-BAs play a more important role in the pathogenesis of fibrotic steatohepatitis.

Keywords

Fibrotic steatohepatitis High fat-cholesterol diet Bile acid profiles Correlation analysis 

Supplementary material

10620_2014_3028_MOESM1_ESM.tiff (82 kb)
Supplementary Fig. 1 BSEP (a) and MRP3 (b) protein levels in the livers of rats fed control and HFC diets (n = 6/group). *P < 0.05 indicates differences from control rats. BSEP bile salt export pump, MRP3 multidrug resistance-associated protein-3 (TIFF 82 kb)
10620_2014_3028_MOESM2_ESM.tiff (59 kb)
Supplementary Fig. 2 MRP2 (a) and MRP1 (b) mRNA levels in the livers of rats fed control and HFC diets (n = 6/group). *P < 0.05 indicates differences from control rats. MRP2 multidrug resistance-associated protein-2, MRP1 multidrug resistance-associated protein-1 (TIFF 58 kb)

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Xiaofang Jia
    • 1
  • Yudai Suzuki
    • 2
  • Hisao Naito
    • 1
  • Husna Yetti
    • 1
  • Kazuya Kitamori
    • 1
    • 3
  • Yumi Hayashi
    • 1
  • Rina Kaneko
    • 2
  • Mina Nomura
    • 2
  • Yukio Yamori
    • 4
  • Kei Zaitsu
    • 2
  • Masashi Kato
    • 1
  • Akira Ishii
    • 2
  • Tamie Nakajima
    • 1
    • 5
  1. 1.Department of Occupational and Environmental HealthNagoya University Graduate School of MedicineNagoyaJapan
  2. 2.Department of Legal Medicine and BioethicsNagoya University Graduate School of MedicineNagoyaJapan
  3. 3.College of Human Life and EnvironmentKinjo Gakuin UniversityNagoyaJapan
  4. 4.Institute for World Health DevelopmentMukogawa Women’s UniversityNishinomiyaJapan
  5. 5.College of Life and Health SciencesChubu UniversityKasugaiJapan

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