scholarly journals Comparative analysis of bile acid spectrum in non-alcoholic fatty liver disease and cholelithiasis

2019 ◽  
Vol 91 (2) ◽  
pp. 48-51 ◽  
Author(s):  
Ya M Vakhrushev ◽  
A P Lukashevich ◽  
I A Penkina ◽  
E V Suchkova

Aim. Сomparative studying of changes in the spectrum of bile acids in bile in patients with nonalcoholic fatty liver disease and cholelithiasis. Materials and methods. 140 patients were included in the survey: 50 - with nonalcoholic fatty liver disease and 90 - with cholelithiasis. The diagnosis of nonalcoholic fatty liver disease was established on the basis of ultrasound examination of the liver, the elasticity and fibrosis of liver by using the sonoelastography and liver biopsy. The prestone stage of cholelithiasis was established on the basis of ultrasound examination of the gallbladder and biochemical examination of bile. The level of total cholesterol, triglycerides, alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase and gamma glutamyl transpeptidase were studied using the analyzer "Labsystems" (Finland). The spectrum of bile acids in bile is studied by mass spectrometry on AmazonX apparatus (Bruker Daltonik GmbH, Bremen, Germany). Results and discussion. Biochemical blood test revealed increase of cholesterol, triglycerides, cytolysis markers, and cholestasis, the most pronounced in patients with nonalcoholic fatty liver disease. Biochemical study of bile showed increase of cholesterol, decrease the total amount of bile acids and cholatecholesterol coefficient in the vesicle and hepatic bile in patients with nonalcoholic fatty liver disease and cholelithiasis. Mass spectrometry showed decrease the total amount of free bile acids (choloidal, chenodeoxycholic, deoxycholic) and increase the content of conjugated bile acids (glycocholic, glycodesoxycholic, taurocholic, taurodeoxycholic, ursodeoxycholic), the most pronounced in patients with nonalcoholic fatty liver disease. Conclusion. Unidirectional changes in the spectrum of bile acids in nonalcoholic fatty liver disease and cholelithiasis give reason to believe that the trigger mechanism in the disturbance of bile acids metabolism is the liver. Reduction of primary bile acids, imbalance of phospholipids and cholesterol disrupt the stabilization of bile, resulting in unfavorable conditions in the bile ducts to form stones.

Author(s):  
Jiake Yu ◽  
Hu Zhang ◽  
Liya Chen ◽  
Yufei Ruan ◽  
Yiping Chen ◽  
...  

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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Hongguo Guan ◽  
Yiyan Wang ◽  
Huitao Li ◽  
Qiqi Zhu ◽  
Xiaoheng Li ◽  
...  

Background: 11β-Hydroxysteroid dehydrogenase one is responsible for activating inert glucocorticoid cortisone into biologically active cortisol in humans and may be a novel target for the treatment of nonalcoholic fatty liver disease.Methods: A series of benzylidene cyclopentanone derivatives were synthesized, and the selective inhibitory effects on rat, mouse and human 11β-hydroxysteroid dehydrogenase one and two were screened. The most potent compound [5-bis-(2,6-difluoro-benzylidene)-cyclopentanone] (WZS08), was used to treat nonalcoholic fatty liver disease in mice fed a high-fat-diet for 100 days.Results: WZS08 was the most potent inhibitor of rat, mouse, and human 11β-hydroxysteroid dehydrogenase 1, with half maximum inhibitory concentrations of 378.0, 244.1, and 621.1 nM, respectively, and it did not affect 11β-hydroxysteroid dehydrogenase two at 100 μM. When mice were fed WZS08 (1, 2, and 4 mg/kg) for 100 days, WZS08 significantly lowered the serum insulin levels and insulin index at 4 mg/kg. WZS08 significantly reduced the levels of serum triglycerides, cholesterol, low-density lipoprotein, and hepatic fat ratio at low concentration of 1 mg/kg. It down-regulated Plin2 expression and up-regulated Fabp4 expression at low concentration of 1 mg/kg. It significantly improved the morphology of the non-alcoholic fatty liver.Conclusion: WZS08 selectively inhibits rat, mouse, and human 11β-hydroxysteroid dehydrogenase 1, and can treat non-alcoholic fatty liver disease in a mouse model.


Doctor Ru ◽  
2020 ◽  
Vol 19 (7) ◽  
pp. 21-30
Author(s):  
N.B. Gubergritz ◽  
◽  
N.V. Belyaeva ◽  
T.L. Mozhina ◽  
N.E. Monogarova ◽  
...  

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.


2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Caihua Wang ◽  
Chunpeng Zhu ◽  
Liming Shao ◽  
Jun Ye ◽  
Yimin Shen ◽  
...  

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.


Hepatology ◽  
2015 ◽  
Vol 63 (5) ◽  
pp. 1739-1740 ◽  
Author(s):  
Lucia Carulli ◽  
Chiara Gabbi ◽  
Marco Bertolotti

2015 ◽  
Vol 33 (3) ◽  
pp. 426-432 ◽  
Author(s):  
Arun J. Sanyal

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.


2017 ◽  
Vol 58 (7) ◽  
pp. 1399-1416 ◽  
Author(s):  
Aafke W. F. Janssen ◽  
Tom Houben ◽  
Saeed Katiraei ◽  
Wieneke Dijk ◽  
Lily Boutens ◽  
...  

2019 ◽  
Author(s):  
mostafa Ahmed EL Foly ◽  
lubna Anas Fawaz ◽  
Ashraf Mohammed Osman ◽  
Salwa Hussien Swelam ◽  
Noura Elbakry

Abstract Abstract Background Non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to nonalcoholic steatohepatitis (NASH)leading to fibrosis and potentially cirrhosis, and it is one of the most common causes of liver disease worldwide.NAFLD is associated with other medical conditions suchas metabolic syndrome, obesity, cardiovascular disease and diabetes. Visfatin is an adipocytokine hormone, which exerts an insulin-like effect by binding to the insulin receptor-1, we aim to investigate the correlation between serum Visfatin and both glucose, lipid metabolism and nonalcoholic fatty liver disease in Simple obese children. Methods: This prospective study included 62 children clinically evaluated as obese and 35 apparently healthy children, age and sex matched as controls. Patients were recruited from the emergency department, in-patient wards and out-patient clinics of thepediatric department of EL-Mina University, children's hospital.While controls were collected from healthy school children during day time between September, 2016 and October, 2017. Fasting Visfatin, glucose, hemoglobinA1cand lipid levels were assayed and abdominal ultrasonography was done for detection of NAFLD. Results There was a statistically significant correlation between serum Visfatin level and BMI (p<0.01), cholesterol levels (p< 0.01), triglycerides levels (p< 0.01), LDL levels (p< 0.01), HDL levels (p< 0.01) in both overweight and obese groups. Conclusions: Visfatin plays an important role in regulation of glucose and lipid metabolism, also in inflammation and insulin resistance, suggesting a role in pathogenesis of Non-Alcoholic Fatty Liver Disease (NAFLD). Key words: Non-alcoholic fatty liver disease; metabolic syndrome; Visfatin


2008 ◽  
Vol 31 (5) ◽  
pp. 290 ◽  
Author(s):  
Giovanni Tarantino

The estimated prevalence of NonAlcoholic Fatty Liver Disease in the general population in western countries is about 30%, but it is higher among obese and diabetic people. It is likely that more sophisticated approaches are required to understand its pathogenesis and to develop drug targets. In the meantime, the range of associations between NAFLD and other illnesses broadens. Although association does not mean causation, the link between some diseases and NAFLD suggests a common mechanism.


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