Bile acid metabolism in liver diseases (II)

1968 ◽  
Vol 3 (4) ◽  
pp. 300-300
Author(s):  
H. Ueda ◽  
T. Harada ◽  
M. Shiba ◽  
M. Ihori ◽  
K. Hirota ◽  
...  
Keyword(s):  
Bile Acid ◽  
Liver Diseases ◽  
Acid Metabolism ◽  
Bile Acid Metabolism

A nontumorigenic variant of FGF19 treats cholestatic liver diseases

2014 ◽  
Vol 6 (247) ◽  
pp. 247ra100-247ra100 ◽  
Author(s):  
Jian Luo ◽  
Brian Ko ◽  
Michael Elliott ◽  
Mei Zhou ◽  
Darrin A. Lindhout ◽  
...  
Keyword(s):  
Bile Acid ◽  
Liver Diseases ◽  
Acid Metabolism ◽  
Prolonged Exposure ◽  
Surrogate Marker ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Bile Acid Metabolism ◽  
Hepatic Bile ◽  
Healthy Human

Hepatic accumulation of bile acids is central to the pathogenesis of cholestatic liver diseases. Endocrine hormone fibroblast growth factor 19 (FGF19) may reduce hepatic bile acid levels through modulation of bile acid synthesis and prevent subsequent liver damage. However, FGF19 has also been implicated in hepatocellular carcinogenesis, and consequently, the potential risk from prolonged exposure to supraphysiological levels of the hormone represents a major hurdle for developing an FGF19-based therapy. We describe a nontumorigenic FGF19 variant, M70, which regulates bile acid metabolism and, through inhibition of bile acid synthesis and reduction of excess hepatic bile acid accumulation, protects mice from liver injury induced by either extrahepatic or intrahepatic cholestasis. Administration of M70 in healthy human volunteers potently reduces serum levels of 7α-hydroxy-4-cholesten-3-one, a surrogate marker for the hepatic activity of cholesterol 7α-hydroxylase (CYP7A1), the enzyme responsible for catalyzing the first and rate-limiting step in the classical bile acid synthetic pathway. This study provides direct evidence for the regulation of bile acid metabolism by FGF19 pathway in humans. On the basis of these results, the development of nontumorigenic FGF19 variants capable of modulating CYP7A1 expression represents an effective approach for the prevention and treatment of cholestatic liver diseases as well as potentially for other disorders associated with bile acid dysregulation.

Allopurinol Protects Against Cholestatic Liver Injury in Mice Not Through Depletion of Uric Acid

2021 ◽  
Author(s):  
Jing Liu ◽  
Yang Fan ◽  
Hang Yu ◽  
Tong Xu ◽  
Chunze Zhang ◽  
...  
Keyword(s):  
Uric Acid ◽  
Bile Acid ◽  
Liver Injury ◽  
Liver Diseases ◽  
Acid Metabolism ◽  
Glutathione Depletion ◽  
Bile Acid Metabolism ◽  
New Perspective ◽  
Cholestatic Liver Injury

Abstract Cholestasis is one of the most severe manifestations of liver injury and has limited therapeutic options. Allopurinol (AP), an inhibitor of uric acid (UA) synthesis, was reported to prevent liver damage in several liver diseases. However, whether AP protects against intrahepatic cholestatic liver injury and what is the role of UA in the pathogenesis of cholestasis remain unknown. In this study, we reported that AP attenuated liver injury in a mouse model of intrahepatic cholestasis induced by alpha-naphthylisothiocyanate (ANIT). AP showed no significant effect on glutathione depletion, inflammation, or bile acid metabolism in livers of ANIT-treated mice. Instead, AP significantly improved fatty acid β-oxidation in livers of ANIT-treated mice, which was associated with activation of PPARα. The protective effect of AP on cholestatic liver injury was not attributable to the depletion of UA, because both exogenous and endogenous UA prevented liver injury in ANIT-treated mice via inhibition of NF-kB-mediated inflammation. In conclusion, the present study provides a new perspective for the therapeutic use of AP and the role of UA in cholestatic liver injury.

T cell mediated cholangitis alters bile acid metabolism

2018 ◽  
Vol 56 (01) ◽  
pp. E2-E89
Author(s):  
F Glaser ◽  
C John ◽  
B Engel ◽  
B Höh ◽  
S Weidemann ◽  
...  
Keyword(s):  
Bile Acid ◽  
T Cell ◽  
Acid Metabolism ◽  
Bile Acid Metabolism

Combined use of epigallocatechin-3-gallate (EGCG) and caffeine in low doses exhibits marked anti-obesity synergy through regulation of gut microbiota and bile acid metabolism

2021 ◽  
Author(s):  
Ming-zhi Zhu ◽  
Fang Zhou ◽  
Jian Ouyang ◽  
Qi-ye Wang ◽  
Yi-long Li ◽  
...  
Keyword(s):  
Bile Acid ◽  
Synergistic Effect ◽  
Gut Microbiota ◽  
Acid Metabolism ◽  
Bile Acid Metabolism ◽  
Low Doses ◽  
Combined Use

Combined use of epigallocatechin-3-gallate (EGCG) and caffeine in low doses exhibits marked anti-obesity synergy. The synergistic effect may be attributed to regulation of gut microbiota and BA metabolism.

Sign in / Sign up

Export Citation Format

Share Document