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 - 01-01-2014

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Chenodeoxycholic Acid
Fatty Liver
Bile Acids and Salts
Glycine
Liver
Cholic Acid
Cholesterol
Deoxycholic Acid
Fats
Alanine Transaminase
Wounds and Injuries
Ursodeoxycholic Acid
High Fat Diet
Tandem Mass Spectrometry
Serum
Liquid Chromatography
Liver Diseases
Homeostasis
Stroke

All Science Journal Classification (ASJC) codes

  • Physiology
  • Gastroenterology

Cite this

Jia, Xiaofang ; Suzuki, Yudai ; Naito, Hisao ; Yetti, Husna ; Kitamori, Kazuya ; Hayashi, Yumi ; Kaneko, Rina ; Nomura, Mina ; Yamori, Yukio ; Zaitsu, Kei ; Kato, Masashi ; Ishii, Akira ; Nakajima, Tamie. / A possible role of chenodeoxycholic acid and glycine-conjugated bile acids in fibrotic steatohepatitis in a dietary rat model. In: Digestive Diseases and Sciences. 2014 ; Vol. 59, No. 7. pp. 1490-1501.
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title = "A possible role of chenodeoxycholic acid and glycine-conjugated bile acids in fibrotic steatohepatitis in a dietary rat model",
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.",
author = "Xiaofang Jia and Yudai Suzuki and Hisao Naito and Husna Yetti and Kazuya Kitamori and Yumi Hayashi and Rina Kaneko and Mina Nomura and Yukio Yamori and Kei Zaitsu and Masashi Kato and Akira Ishii and Tamie Nakajima",
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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, vol. 59, no. 7, pp. 1490-1501. https://doi.org/10.1007/s10620-014-3028-3

A possible role of chenodeoxycholic acid and glycine-conjugated bile acids in fibrotic steatohepatitis in a dietary rat model. / Jia, Xiaofang; Suzuki, Yudai; Naito, Hisao; Yetti, Husna; Kitamori, Kazuya; Hayashi, Yumi; Kaneko, Rina; Nomura, Mina; Yamori, Yukio; Zaitsu, Kei; Kato, Masashi; Ishii, Akira; Nakajima, Tamie.

In: Digestive Diseases and Sciences, Vol. 59, No. 7, 01.01.2014, p. 1490-1501.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A possible role of chenodeoxycholic acid and glycine-conjugated bile acids in fibrotic steatohepatitis in a dietary rat model

AU - Jia, Xiaofang

AU - Suzuki, Yudai

AU - Naito, Hisao

AU - Yetti, Husna

AU - Kitamori, Kazuya

AU - Hayashi, Yumi

AU - Kaneko, Rina

AU - Nomura, Mina

AU - Yamori, Yukio

AU - Zaitsu, Kei

AU - Kato, Masashi

AU - Ishii, Akira

AU - Nakajima, Tamie

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

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JO - American Journal of Digestive Diseases

JF - American Journal of Digestive Diseases

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