Pathophysiology of Nonalcoholic Fatty Liver Disease: Lifestyle-Gut-Gene Interaction

2016 ◽  
Vol 34 (Suppl. 1) ◽  
pp. 3-10 ◽  
Author(s):  
Arianna Mazzotti ◽  
Maria Turchese Caletti ◽  
Anna Simona Sasdelli ◽  
Lucia Brodosi ◽  
Giulio Marchesini
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Genetic Factors ◽  
De Novo Lipogenesis ◽  
Primary Role ◽  
Nonalcoholic Fatty Liver ◽  
Increased Risk

Background: The accumulation of fat droplets in the hepatic parenchyma is driven by several factors, synergistically acting to increase triglyceride flow to the liver (diet and metabolic factors, endotoxemia from gut microbiota, genetic factors). Key Messages: In the presence of unhealthy lifestyles and behavioral factors, leading to enlarged adipose tissue and insulin resistance (IR), both lipolysis and de novo lipogenesis are expected to increase the risk of hepatic lipid depots, in association with high calorie (either high-fat or high-carbohydrate) diets. The gut microbiota may also be involved via obesity, IR and hepatic inflammation generated by gut-derived toxic factors. Finally, several data also support a primary role of genetic factors. A few gene polymorphisms have also been associated with the risk of nonalcoholic fatty liver disease development and nonalcoholic steatohepatitis progression to more fibrosis and advanced liver disease. In a few cases (e.g., patatin-like phospholipase domain-containing 3/adiponutrin), steatosis carries a high risk of both liver disease and cardiovascular morbidity/mortality; in other cases (e.g., transmembrane 6 superfamily 2 human gene), dissociation has been observed between the increased risk of liver disease versus cardiovascular disease. Conclusions: A variable interplay between the genetic background and the metabolic milieu is the likely physiopathologic mechanism involved in individual cases, which must be considered for implementing effective treatment strategies.

scholarly journals Nonalcoholic fatty liver disease and the risk of atrial fibrillation stratified by body mass index: a nationwide population-based study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
So-Ryoung Lee ◽  
Kyung-Do Han ◽  
Eue-Keun Choi ◽  
Seil Oh ◽  
Gregory Y. H. Lip
Keyword(s):  
Atrial Fibrillation ◽  
Body Mass Index ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Body Mass ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Increased Risk ◽  
The Impact

AbstractWe evaluated the association between nonalcoholic fatty liver disease (NAFLD) and incident atrial fibrillation (AF) and analyzed the impact of NAFLD on AF risk in relation to body mass index (BMI). A total of 8,048,055 subjects without significant liver disease who were available fatty liver index (FLI) values were included. Subjects were categorized into 3 groups based on FLI: < 30, 30 to < 60, and ≥ 60. During a median 8-year of follow-up, 534,442 subjects were newly diagnosed as AF (8.27 per 1000 person-years). Higher FLI was associated with an increased risk of AF (hazard ratio [HR] 1.053, 95% confidence interval [CI] 1.046–1.060 in 30 ≤ FLI < 60, and HR 1.115, 95% CI 1.106–1.125 in FLI ≥ 60). In underweight subjects (BMI < 18.5 kg/m2), higher FLI raised the risk of AF (by 1.6-fold in 30 ≤ FLI < 60 and by twofold in FLI ≥ 60). In normal- and overweight subjects, higher FLI was associated with an increased risk of AF, but the HRs were attenuated. In obese subjects, higher FLI was not associated with higher risk of AF. NAFLD as assessed by FLI was independently associated with an increased risk of AF in nonobese subjects with BMI < 25 kg/m2. The impact of NAFLD on AF risk was accentuated in lean subjects with underweight.

scholarly journals Concepts and Treatment Approaches in Nonalcoholic Fatty Liver Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Dina L. Halegoua-De Marzio ◽  
Jonathan M. Fenkel
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
De Novo ◽  
Imaging Techniques ◽  
De Novo Lipogenesis ◽  
Central Adiposity ◽  
Preventative Care ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) affects up to 30% of adults and is the most common liver disease in Western nations. NAFLD is associated with central adiposity, insulin resistance, type 2 diabetes mellitus, hyperlipidemia, and cardiovascular disease. It encompasses the entire spectrum of fatty liver diseases from simple steatosis to nonalcoholic steatohepatitis (NASH) with lobular/portal inflammation, hepatocellular necrosis, and fibrosis. Of those who develop NASH, 15–25% will progress to end stage liver disease and hepatocellular carcinoma over 10–20 years. Its pathogenesis is complex, and involves a state of lipid accumulation due to increased uptake of free fatty acids into the liver, impaired fatty acid beta oxidation, and increased incidence of de novo lipogenesis. Plasma aminotransferases and liver ultrasound are helpful in the diagnosis of NAFLD/NASH, but a liver biopsy is often required for definitive diagnosis. Many new plasma biomarkers and imaging techniques are now available that should improve the ability to diagnose NAFLD noninvasively Due to its complexity and extrahepatic complications, treatment of NAFLD requires a multidisciplinary approach with excellent preventative care, management, and treatment. This review will evaluate our current understanding of NAFLD, with a focus on existing therapeutic approaches and potential pharmacological developments.

Nonalcoholic Fatty Liver Disease and Cardiovascular Disease: Overlapping Mechanisms

2021 ◽  
Author(s):  
Søren Møller ◽  
Nina Kimer ◽  
Thit Kronborg ◽  
Josephine Grandt ◽  
Jens Dahlgaard Hove ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Severe Form ◽  
Nonalcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Near Future

AbstractNonalcoholic fatty liver disease (NAFLD) denotes a condition with excess fat in the liver. The prevalence of NAFLD is increasing, averaging > 25% of the Western population. In 25% of the patients, NAFLD progresses to its more severe form: nonalcoholic steatohepatitis and >25% of these progress to cirrhosis following activation of inflammatory and fibrotic processes. NAFLD is associated with obesity, type 2 diabetes, and the metabolic syndrome and represents a considerable and increasing health burden. In the near future, NAFLD cirrhosis is expected to be the most common cause for liver transplantation. NAFLD patients have an increased risk of developing cardiovascular disease as well as liver-related morbidity. In addition, hepatic steatosis itself appears to represent an independent cardiovascular risk factor. In the present review, we provide an overview of the overlapping mechanisms and prevalence of NAFLD and cardiovascular disease.

scholarly journals Gut Microbiota Changes in Nonalcoholic Fatty Liver Disease and Concomitant Cardiovascular Diseases

2020 ◽  
Author(s):  
Olena H. Kurinna
Keyword(s):  
Liver Disease ◽  
Cardiovascular Diseases ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Statistical Significance ◽  
Microbiota Composition ◽  
Nonalcoholic Fatty Liver ◽  
Gut Microbiota Composition

AbstractNonalcoholic fatty liver disease (NAFLD) bears serious economic consequences for the health care system worldwide and Ukraine, in particular. Cardiovascular diseases (CVD) are the main cause of mortality in NAFLD patients. Changes in the gut microbiota composition can be regarded as a potential mechanism of CVD in NAFLD patients.The purpose of this work was to investigate changes in major gut microbiota phylotypes, Bacteroidetes, Firmicutes and Actinobacteria with quantification of Firmicutes/Bacteroidetes in NAFLD patients with concomitant CVD.The author enrolled 120 NAFLD subjects (25 with concomitant arterial hypertension (AH) and 24 with coronary artery disease (CAD)). The gut microbiota composition was assessed by qPCR.Resultsthe author found a marked tendency towards an increase in the concentration of Bacteroidetes (by 37.11% and 21.30%, respectively) with a decrease in Firmicutes (by 7.38% and 7.77%, respectively) in both groups with comorbid CAD and AH with the identified changes not reaching a statistical significance. The author quantified a statistically significant decrease in the concentration of Actinobacteria in patients with NAFLD with concomitant CAD at 41.37% (p<0.05) as compared with those with an isolated NAFLD. In patients with concomitant AH, the content of Actinobacteria dropped by 12.35%, which was statistically insignificant.Conclusionsthe author established changes in the intestinal microbiota, namely decrease in Actinobacteria in patients with CAD, which requires further research.

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

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.

scholarly journals Lean Nonalcoholic Fatty Liver Disease and Risk of Incident Diabetes in a Euglycemic Population Receiving Health Checkups: A Cohort Study

2020 ◽  
Author(s):  
Limin Wei ◽  
Xin Cheng ◽  
Yulong Luo ◽  
Rongxuan Yang ◽  
Zitong Lei ◽  
...  
Keyword(s):  
Cohort Study ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Incident Diabetes ◽  
Benign Condition ◽  
Nonalcoholic Fatty Liver ◽  
Increased Risk ◽  
Lean Nafld

Abstract Background: Although recent evidence suggests that nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance and an increased risk of diabetes, the association between lean NAFLD and incident diabetes is unclear. This study aimed to investigate whether lean NAFLD and overweight/obese NAFLD have similar or dissimilar effects on the risk of new-onset diabetes.Methods: A longitudinal study was performed in 14,482 euglycemic adults who participated in a health check-up program. Fatty liver was diagnosed by abdominal ultrasonography. The outcome of interest was incident diabetes.Cox proportional hazards regression models were applied to calculate HRs with 95% CIs for future diabetes risk.Results: During the median 6.0 years of follow-up, 356 cases of diabetes occurred. Despite a low probability of hepatic fibrosis indicated by the BAAT score, lean NAFLD was positively associated with an increased risk of diabetes. Moreover, after adjusting for sociodemographic and potential confounders, the fullyadjusted HRs (95% CIs) for incident diabetes between lean NAFLD and overweight/obese NAFLD to the reference (lean without NAFLD) were 2.58 (95% CI 1.68 to 3.97) and 2.52 (95% CI 1.79 to 3.55), respectively. In post hoc analysis, the HR (95% CI) for diabetes comparing lean NAFLD to obese/overweight NAFLD was 1.02 (95% CI 0.68 to 1.54, p = 0.909). The results were robust to challenges in multiple subgroup analyses and appeared to be more pronounced for female participants (p for interaction = 0.005).Conclusions: In this cohort study, lean patients with NAFLD had a risk of incident type 2 diabetes similar to that of overweight/obese ones with NAFLD. These findings suggest that lean NAFLD is not a benign condition. Further investigations are needed to gain a better understanding of the pathogenesis and natural history of NAFLD in lean subjects.

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