A possible role of chenodeoxycholic acid and glycine-conjugated bile acids in fibrotic steatohepatitis in a dietary rat model.
OBJECTIVE
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.
Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
Xiaofang
X
Jia
Yudai
Y
Suzuki
Hisao
H
Naito
Husna
H
Yetti
Kazuya
K
Kitamori
Yumi
Y
Hayashi
Rina
R
Kaneko
Mina
M
Nomura
Yukio
Y
Yamori
Kei
K
Zaitsu
Masashi
M
Kato
Akira
A
Ishii
Tamie
T
Nakajima
D000818:Animals; D015415:Biomarkers; D002635:Chenodeoxycholic Acid / Q000378:metabolism*; D019826:Cholic Acid / Q000378:metabolism*; D002853:Chromatography, Liquid; D003840:Deoxycholic Acid / Q000378:metabolism*; D059305:Diet, High-Fat; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D011897:Random Allocation; D051381:Rats; D053719:Tandem Mass Spectrometry
D015415:Biomarkers; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D019826:Cholic Acid