Bile Acids and Nonalcoholic Fatty Liver and Pancreas Disease: Going Together?

Objective of the Review: to analyse changes in bile acids (BA) metabolism due to nonalcoholic fatty liver disease (NAFL), nonalcoholic fatty pancreas disease (NAFP); to assess the efficiency of ursodeoxycholic acid (UDCA) for their correction. Key Points. NAFL and NAFP have much in common, including BA synthesis imbalance and reduced farnesoid X receptor (FXR) expression. One possible therapy of NAFL and NAFP is BA synthesis correction and increase in FXR expression using FXR agonists. The article discusses clinical and experimental trials of the efficiency of selective FXR agonist — UDCA — in NAFL and NAFP. Conclusion. The multifactorial UDCA mechanism of action including anti-inflammatory, antioxidant, cytoprotective and antiapoptotic actions, can normalise carbohydrate, lipid metabolism and activate FXR; it can justify medicine inclusion into NAFL and NAFP therapeutic regimens. Keywords: nonalcoholic fatty liver disease, nonalcoholic fatty pancreas disease, ursodeoxycholic acid.

Download Full-text

Use of Farnesoid X Receptor Agonists to Treat Nonalcoholic Fatty Liver Disease

Digestive Diseases ◽

10.1159/000371698 ◽

2015 ◽

Vol 33 (3) ◽

pp. 426-432 ◽

Cited By ~ 7

Author(s):

Arun J. Sanyal

Keyword(s):

Insulin Resistance ◽

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Bile Acids ◽

Fatty Liver Disease ◽

Animal Studies ◽

Farnesoid X Receptor ◽

Nonalcoholic Fatty Liver ◽

Improve Insulin Resistance

Nonalcoholic fatty liver disease is a common cause of liver related morbidity and mortality. It is closely linked to underlying insulin resistance. It has recently been shown that bile acids modulate insulin signaling and can improve insulin resistance in cell based and animal studies. These effects are mediated in part by activation of farnesoid x receptors by bile acids. In human studies, FXR agonists improve insulin resistance and have recently been shown to improve NAFLD. The basis for the use of FXR agonists for the treatment of NAFLD and early human experience with such agents is reviewed in this paper.

Download Full-text

Nonalcoholic fatty pancreas disease and Nonalcoholic fatty liver disease: more than ectopic fat

Clinical Endocrinology ◽

10.1111/cen.12862 ◽

2015 ◽

Vol 83 (5) ◽

pp. 656-662 ◽

Cited By ~ 36

Author(s):

C. Della Corte ◽

A. Mosca ◽

F. Majo ◽

V. Lucidi ◽

N. Panera ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Ectopic Fat ◽

Pancreas Disease ◽

Nonalcoholic Fatty Liver ◽

Fatty Pancreas

Download Full-text

1274 URSODEOXYCHOLIC ACID IMPROVES HEPATIC STEATOSIS AND INFLAMMATION BY THE FARNESOID X RECEPTOR IN OBESE MODEL WITH NONALCOHOLIC FATTY LIVER DISEASE

Journal of Hepatology ◽

10.1016/s0168-8278(13)61275-1 ◽

2013 ◽

Vol 58 ◽

pp. S515

Author(s):

H. Liu ◽

J. Liao ◽

T. Lee ◽

H. Chang ◽

H. Lin

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Ursodeoxycholic Acid ◽

Nonalcoholic Fatty Liver Disease ◽

Hepatic Steatosis ◽

Fatty Liver Disease ◽

Farnesoid X Receptor ◽

Nonalcoholic Fatty Liver

Download Full-text

Nonalcoholic Fatty Liver Disease Is Related to Nonalcoholic Fatty Pancreas Disease

Pancreas ◽

10.1097/mpa.0b013e3181f6fce2 ◽

2010 ◽

Vol 39 (8) ◽

pp. 1185-1190 ◽

Cited By ~ 74

Author(s):

Erwin-Jan M. van Geenen ◽

Mark M. Smits ◽

Tim C.M.A. Schreuder ◽

Donald L. van der Peet ◽

Elisabeth Bloemena ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Pancreas Disease ◽

Nonalcoholic Fatty Liver ◽

Fatty Pancreas

Download Full-text

Emodin palliates high-fat diet-induced nonalcoholic fatty liver disease in mice via activating the farnesoid X receptor pathway

Journal of Ethnopharmacology ◽

10.1016/j.jep.2021.114340 ◽

2021 ◽

pp. 114340

Author(s):

Chuangpeng Shen ◽

Zhisen Pan ◽

Shuangcheng Wu ◽

Mingxuan Zheng ◽

Chong Zhong ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Farnesoid X Receptor ◽

High Fat ◽

Nonalcoholic Fatty Liver

Download Full-text

Efficacy of Ursodeoxycholic Acid in Nonalcoholic Fatty Liver Disease: An Updated Meta-Analysis of Randomized Controlled Trials

10.21203/rs.2.15906/v1 ◽

2019 ◽

Author(s):

Wenyue Zhang ◽

Yao Tang ◽

Juan Huang ◽

Hong Ren ◽

Yixuan Yang ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Ursodeoxycholic Acid ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Total Bilirubin ◽

Meta Analysis ◽

Nonalcoholic Fatty Liver ◽

Randomized Controlled

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is a kind of chronic liver disease among general population. Recent years, more and more new experiments have made the role of ursodeoxycholic acid (UDCA) become clearer. In this meta-analysis, we analyzed the efficacy of ursodeoxycholic acid (UDCA) for the treatment of nonalcoholic fatty liver disease (NAFLD). Methods We searched the Web of Science, Pubmed, Embase and Cochrane library databases for relavent studies published before March 1, 2019. We examined 134 randomized controlled trials (RCTs) that investigated the effectiveness of UDCA in NAFLD against placebo or other treatments. Next, we conducted meta-analysis by Stata(version 12.0) to examine the change among several indices: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), Alkaline phosphatase (AP), total bilirubin and albumin. Results Following the application of different inclusion and exclusion criteria, 9 articles with 1106 participants were finally selected. The forest plot displayed that UDCA treatment can significantly decrease the ALT levels among the NAFLD patients (SMD=0.17,95%CI [0.03 to 0.3], P=0.07). However, UDCA treatment did not significantly affect the AST, GGT, AP, total bilirubin and albumin levels. Further, the subgroup analyses suggested the significant role of UDCA treatment in different geographical regions, age group and treatment duration (P=0.003 in people from Europe, P=0.001 in people older than 50 years and P=0.008 in longer duration(>6 months)). Conclusion In this study, several indices we analyzed among 9 articles. UDCA treatment was found beneficial in lowering the ALT levels in NAFLD patients. The remaining indices like AST, GGT, AP showed non-significant changes in this analysis. This could be attributed for the insufficient number of trials because all parameters were not analyzed in each individual RCT. Therefore, future meta-analysis will be required to fully confirm and validate the efficacy of UDCA in NAFL.

Download Full-text

Disease-Associated Gut Microbiota Reduces the Profile of Secondary Bile Acids in Pediatric Nonalcoholic Fatty Liver Disease

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.698852 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jiake Yu ◽

Hu Zhang ◽

Liya Chen ◽

Yufei Ruan ◽

Yiping Chen ◽

...

Keyword(s):

Liver Disease ◽

Bile Acid ◽

Gut Microbiota ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Bile Acids ◽

Fatty Liver Disease ◽

Healthy Children ◽

Nonalcoholic Fatty Liver ◽

Secondary Bile Acids

Children with nonalcoholic fatty liver disease (NAFLD) display an altered gut microbiota compared with healthy children. However, little is known about the fecal bile acid profiles and their association with gut microbiota dysbiosis in pediatric NAFLD. A total of 68 children were enrolled in this study, including 32 NAFLD patients and 36 healthy children. Fecal samples were collected and analyzed by metagenomic sequencing to determine the changes in the gut microbiota of children with NAFLD, and an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system was used to quantify the concentrations of primary and secondary bile acids. The associations between the gut microbiota and concentrations of primary and secondary bile acids in the fecal samples were then analyzed. We found that children with NAFLD exhibited reduced levels of secondary bile acids and alterations in bile acid biotransforming-related bacteria in the feces. Notably, the decrease in Eubacterium and Ruminococcaceae bacteria, which express bile salt hydrolase and 7α-dehydroxylase, was significantly positively correlated with the level of fecal lithocholic acid (LCA). However, the level of fecal LCA was negatively associated with the abundance of the potential pathogen Escherichia coli that was enriched in children with NAFLD. Pediatric NAFLD is characterized by an altered profile of gut microbiota and fecal bile acids. This study demonstrates that the disease-associated gut microbiota is linked with decreased concentrations of secondary bile acids in the feces. The disease-associated gut microbiota likely inhibits the conversion of primary to secondary bile acids.

Download Full-text

Role of Bile Acids in Dysbiosis and Treatment of Nonalcoholic Fatty Liver Disease

Mediators of Inflammation ◽

10.1155/2019/7659509 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 8

Author(s):

Caihua Wang ◽

Chunpeng Zhu ◽

Liming Shao ◽

Jun Ye ◽

Yimin Shen ◽

...

Keyword(s):

Liver Disease ◽

Bile Acid ◽

Gut Microbiota ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Bile Acids ◽

Fatty Liver Disease ◽

Nonalcoholic Fatty Liver ◽

Bile Acid Receptors

Nonalcoholic fatty liver disease (NAFLD) is a major health threat around the world and is characterized by dysbiosis. Primary bile acids are synthesized in the liver and converted into secondary bile acids by gut microbiota. Recent studies support the role of bile acids in modulating dysbiosis and NAFLD, while the mechanisms are not well elucidated. Dysbiosis may alter the size and the composition of the bile acid pool, resulting in reduced signaling of bile acid receptors such as farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). These receptors are essential in lipid and glucose metabolism, and impaired bile acid signaling may cause NAFLD. Bile acids also reciprocally regulate the gut microbiota directly via antibacterial activity and indirectly via FXR. Therefore, bile acid signaling is closely linked to dysbiosis and NAFLD. During the past decade, stimulation of bile acid receptors with their agonists has been extensively explored for the treatment of NAFLD in both animal models and clinical trials. Early evidence has suggested the potential of bile acid receptor agonists in NAFLD management, but their long-term safety and effectiveness need further clarification.

Download Full-text