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

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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.

Original languageEnglish
Pages (from-to)1490-1501
Number of pages12
JournalDigestive Diseases and Sciences
Volume59
Issue number7
DOIs
Publication statusPublished - 04-2014

All Science Journal Classification (ASJC) codes

  • Physiology
  • Gastroenterology

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    Jia, X., Suzuki, Y., Naito, H., Yetti, H., Kitamori, K., Hayashi, Y., Kaneko, R., Nomura, M., Yamori, Y., Zaitsu, K., Kato, M., Ishii, A., & Nakajima, T. (2014). A possible role of chenodeoxycholic acid and glycine-conjugated bile acids in fibrotic steatohepatitis in a dietary rat model. Digestive Diseases and Sciences, 59(7), 1490-1501. https://doi.org/10.1007/s10620-014-3028-3