scholarly journals Why Bile Acids Are So Important in Non-Alcoholic Fatty Liver Disease (NAFLD) Progression

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1358 ◽  
Author(s):  
Aline Gottlieb ◽  
Ali Canbay
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
The Body ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Primary Biliary Cholangitis ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a complex disease, affecting not just the liver, but also all other organs in the body. Despite an increasing amount of people worldwide developing NAFLD and having it progress to non-alcoholic steatohepatitis (NASH) and potentially cirrhosis, there is still no approved therapy. Therefore, huge efforts are being made to find and develop a successful treatment. One of the special interests is understanding the liver–gut axis and especially the role of bile acids in the progression of NAFLD. Farnesoid X receptor (FXR)-agonists have been approved und used in other liver diseases, such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), and have shown signs of being able to decrease inflammation and potentially steatosis. This review will mainly focus on targets/ligands that play an important role in bile acid metabolism and give an overview of ongoing clinical as well as pre-clinical trials. With the complexity of the issue, we did not aim at giving a complete review, rather highlighting important targets and potential treatments that could be approved for NAFLD/NASH treatment within the next few years.

scholarly journals A look at new therapeutic opportunities in patients with non-alcoholic fatty liver disease

2019 ◽  
Vol 16 (3) ◽  
pp. 37-45
Author(s):  
Ekaterina E. Mishina ◽  
Alexander Y. Mayorov ◽  
Apollinariya V. Bogolyubova ◽  
Pavel O. Bogomolov ◽  
Maria V. Matsievich ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Alcoholic Fatty Liver ◽  
Inflammatory Processes ◽  
Active Research ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, and is considered to be the liver manifestation of metabolic syndrome. Currently, there is no etiotropic treatment of NAFLD, so an active research for new methods of treatment is underway. In the meantime, drugs are used to treat comorbid conditions, such as dyslipidemia, arterial hypertension, obesity, type 2 diabetes, which are present in varying degrees in patients. This review considers medications that are used in patients with NAFLD and related concomitant features, and also describes new strategies for regressing changes in liver tissue in NAFLD. In our opinion, one of the promising groups of drugs are agonists of the farnesoid X receptor (FXR). FXR belongs to the group of nuclear receptors, which are ligand-activated transcription factors that regulate the genes involved in metabolism. FXR agonists can claim to be a new promising drug for the treatment of NAFLD and related diseases influencing carbohydrate metabolism, fat metabolism, bile acid metabolism, as well as inflammatory processes in the liver to ensure metabolic homeostasis.

scholarly journals Aryl Hydrocarbon Receptor (AhR) Activation by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) Dose-Dependently Shifts the Gut Microbiome Consistent with the Progression of Non-Alcoholic Fatty Liver Disease

2021 ◽  
Vol 22 (22) ◽  
pp. 12431
Author(s):  
Russell R. Fling ◽  
Timothy R. Zacharewski
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Fatty Liver ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Acid Metabolism ◽  
Bile Acid Metabolism ◽  
Alcoholic Fatty Liver ◽  
Dose Dependent ◽  
Alcoholic Fatty Liver Disease

Gut dysbiosis with disrupted enterohepatic bile acid metabolism is commonly associated with non-alcoholic fatty liver disease (NAFLD) and recapitulated in a NAFLD-phenotype elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice. TCDD induces hepatic fat accumulation and increases levels of secondary bile acids, including taurolithocholic acid and deoxycholic acid (microbial modified bile acids involved in host bile acid regulation signaling pathways). To investigate the effects of TCDD on the gut microbiota, the cecum contents of male C57BL/6 mice orally gavaged with sesame oil vehicle or 0.3, 3, or 30 µg/kg TCDD were examined using shotgun metagenomic sequencing. Taxonomic analysis identified dose-dependent increases in Lactobacillus species (i.e., Lactobacillus reuteri). Increased species were also associated with dose-dependent increases in bile salt hydrolase sequences, responsible for deconjugation reactions in secondary bile acid metabolism. Increased L. reuteri levels were further associated with mevalonate-dependent isopentenyl diphosphate (IPP) biosynthesis and o-succinylbenzoate synthase, a menaquinone biosynthesis associated gene. Analysis of the gut microbiomes from cirrhosis patients identified an increased abundance of genes from the mevalonate-dependent IPP biosynthesis as well as several other menaquinone biosynthesis genes, including o-succinylbenzoate synthase. These results extend the association of lactobacilli with the AhR/intestinal axis in NAFLD progression and highlight the similarities between TCDD-elicited phenotypes in mice to human NAFLD.

scholarly journals Non-Alcoholic Fatty Liver Disease, Bile Acids and Intestinal Microbiota

2018 ◽  
Vol 28 (4) ◽  
pp. 84-90
Author(s):  
R. V. Maslennikov ◽  
Yu. V. Evsyutina
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Bile Acids ◽  
Intestinal Microbiota ◽  
Fatty Liver Disease ◽  
Liver Steatosis ◽  
Bile Acid Metabolism ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Aim.  The aim of the review is to present current data on the relationship between non-alcoholic fatty liver disease (NAFLD) with the metabolic disorders of bile acids (BA) and changes in the composition of the intestinal microbiota.Background.  NAFLD is accompanied by a change in the intestinal microbiotic composition: the proportion of taxa deconjugating BAs increases, while the proportion of taxa converting primary BAs to secondary ones decreases. The number of bacteria forming lipopolysaccharide (LPS) also increases. LPS, entering the liver with the portal vein blood, promotes the development of its inflammation and insulin resistance. The disturbance of bile acid metabolism through the effect on the FXR and TGR5 receptors also leads to insulin resistance and liver steatosis. FXR probiotics and agonists are promising drugs for the NAFLD treatment.Conclusion.  In the course of NAFLD, a change in the composition of the intestinal microbiota is observed, which contributes to the development of inflammation in the liver and disrupts the metabolism of bile acids, leading to insulin resistance. 

scholarly journals Frequency of non-alcoholic fatty liver disease in a series of forensic cases in Mexico

2021 ◽  
Vol 20 (2) ◽  
Author(s):  
Ana Laura Calderón-Garcidueñas
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
The Body ◽  
Mexican Population ◽  
Alcoholic Fatty Liver ◽  
Abdominal Perimeter ◽  
Asymptomatic Individuals ◽  
Del Rio ◽  
Alcoholic Fatty Liver Disease

The Mexican population is overweight (34%) and obese (21%). Obesity is a risk factor for non-alcoholic fatty liver disease (NAFLD). Most studies of the frequency and prevalence of NAFLD have been performed using ultrasonography. In Mexico, ultrasound-based studies have shown a prevalence of NAFLD of 15.7 to 17 %. Objective. The objective was to determine the frequency of NAFLD in apparently asymptomatic individuals who died instantly in a traffic accident and with not known background of liver disease. Material and Methods. Autopsies were performed at the Coroner’s Office in the Municipality of Boca del Río, Mexico, during the period from January to December 2016. The variables studied included age, sex, weight, height, abdominal perimeter, fat panicle-thickness, main cause of death, and liver biopsy (NASH CRN classification). Results. Of the 32 cases studied, 78.1 % were males. Average age was 48 years (range 20-80 years). The body mass index range (BMI) was 17-33. A 34% of cases had NAFLD. 27.3 % of the cases with NAFLD had a normal BMI. Conclusions. This postmortem study showed a higher frequency of asymptomatic hepatic steatosis than previously reported in the Mexican population. The establishment of timely national measures to detect and prevent complications of NFALD is necessary.

Non-alcoholic fatty liver disease – discussed under the light of Unani medicine

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mohd Riyazuddin ◽  
Arisha Shahid
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Dietary Habits ◽  
Primary Source ◽  
Developed Countries ◽  
The Body ◽  
Excessive Alcohol Consumption ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Abstract Non-alcoholic Fatty Liver Disease (NAFLD) is one of the diseases that have evolved lately into a major challenge for gastroenterologists. Although, the term NAFLD has not been familiar to the medical world since long, other conditions resembling the presentation of NAFLD have been there since primitive times. It is a reversible condition of the liver, wherein large vacuoles of triglyceride fat accumulates in liver cells via the process of steatosis, despite any evidence of excessive alcohol consumption. In the developed countries NAFLD is reported to be the most common liver disorder, with a worldwide prevalence of 6–35%, in India its prevalence has been increasing gradually. Unani physicians have described liver as one of the principal organs of the body. It is the primary source of natural faculties, where the functions of digestion, concoction, absorption and excretion are performed, normally temperament of liver is hot and moist which can get converted to cold due to mutable dietary habits, consumption of fatty and cold food in abundance etc. In Unani System of Medicine, NAFLD has not been described as such, but it can be studied under Su’-i-Mizāj Kabid Bārid due to correlation of most of the symptoms. Its management mainly consists of elimination of morbid matter which is accumulated in the liver and correction of Su’-i-Mizāj Kabid Bārid by using drugs having opposite temperament (Ilaj bil zid).

Unified interpretation of liver stiffness measurement by M and XL probes in non-alcoholic fatty liver disease

Gut ◽  
2019 ◽  
Vol 68 (11) ◽  
pp. 2057-2064 ◽  
Author(s):  
Vincent Wai-Sun Wong ◽  
Marie Irles ◽  
Grace Lai-Hung Wong ◽  
Sarah Shili ◽  
Anthony Wing-Hung Chan ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Transient Elastography ◽  
Liver Stiffness ◽  
The Body ◽  
Liver Stiffness Measurement ◽  
Alcoholic Fatty Liver ◽  
Stiffness Measurement ◽  
Alcoholic Fatty Liver Disease

ObjectiveThe latest model of vibration-controlled transient elastography (VCTE) automatically selects M or XL probe according to patients’ body built. We aim to test the application of a unified interpretation of VCTE results with probes appropriate for the body mass index (BMI) and hypothesise that this approach is not affected by hepatic steatosis.DesignWe prospectively recruited 496 patients with non-alcoholic fatty liver disease who underwent VCTE by both M and XL probes within 1 week before liver biopsy.Results391 (78.8%) and 433 (87.3%) patients had reliable liver stiffness measurement (LSM) (10 successful acquisitions and IQR:median ratio ≤0.30) by M and XL probes, respectively (p<0.001). The area under the receiver operating characteristic curves was similar between the two probes (0.75–0.88 for F2–4, 0.83–0.91 for F4). When used in the same patient, LSM by XL probe was lower than that by M probe (mean difference 2.3 kPa). In contrast, patients with BMI ≥30 kg/m2 had higher LSM regardless of the probe used. When M and XL probes were used in patients with BMI <30 and ≥30 kg/m2, respectively, they yielded nearly identical median LSM at each fibrosis stage and similar diagnostic performance. Severe steatosis did not increase LSM or the rate of false-positive diagnosis by XL probe.ConclusionHigh BMI but not severe steatosis increases LSM. The same LSM cut-offs can be used without further adjustment for steatosis when M and XL probes are used according to the appropriate BMI.

scholarly journals Bile Acids and Dysbiosis in Non-Alcoholic Fatty Liver Disease

PLoS ONE ◽  
2016 ◽  
Vol 11 (5) ◽  
pp. e0151829 ◽  
Author(s):  
Marialena Mouzaki ◽  
Alice Y. Wang ◽  
Robert Bandsma ◽  
Elena M. Comelli ◽  
Bianca M. Arendt ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease
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