Is liver fat detrimental to vessels?: intersections in the pathogenesis of NAFLD and atherosclerosis

2008 ◽  
Vol 115 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Paola Loria ◽  
Amedeo Lonardo ◽  
Giovanni Targher
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Liver Fat ◽  
Cvd Risk ◽  
Alcoholic Fatty Liver ◽  
Insulin Resistant ◽  
Major Player

NAFLD (non-alcoholic fatty liver disease) encompasses the spectrum of fatty liver disease in insulin-resistant individuals who often display T2DM (Type 2 diabetes mellitus) and obesity. The present review highlights the pathophysiological basis and clinical evidence for a possible causal linkage between NAFLD and CVD (cardiovascular disease). The role of traditional and non-traditional CVD risk factors in the pathophysiology of NAFLD is considered in the first part of the review, with the basic science shared by atherogenesis and hepatic steatogenesis discussed in depth in the second part. In conclusion, NAFLD is not an innocent bystander, but a major player in the development and progression of CVD. NAFLD and CVD also share similar molecular mechanisms and targeted treatment strategies. On the research side, studies should focus on interventions aimed at restoring energy homoeostasis in lipotoxic tissues and at improving hepatic (micro)vascular blood supply.

scholarly journals Relationship between Muscle Mass and Non-Alcoholic Fatty Liver Disease

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 122
Author(s):  
Jun-Hyuk Lee ◽  
Hye-Sun Lee ◽  
Byoung-Kwon Lee ◽  
Yu-Jin Kwon ◽  
Ji-Won Lee
Keyword(s):  
Skeletal Muscle ◽  
Risk Factor ◽  
Liver Disease ◽  
Fatty Liver ◽  
Muscle Mass ◽  
Fatty Liver Disease ◽  
Skeletal Muscle Mass ◽  
Liver Fat ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Although sarcopenia is known to be a risk factor for non-alcoholic fatty liver disease (NAFLD), whether NAFLD is a risk factor for the development of sarcopenia is not clear. We investigated relationships between NAFLD and low skeletal muscle mass index (LSMI) using three different datasets. Participants were classified into LSMI and normal groups. LSMI was defined as a body mass index (BMI)-adjusted appendicular skeletal muscle mass <0.789 in men and <0.512 in women or as the sex-specific lowest quintile of BMI-adjusted total skeletal muscle mass. NAFLD was determined according to NAFLD liver fat score or abdominal ultrasonography. The NAFLD groups showed a higher hazard ratios (HRs) with 95% confidence intervals (CIs) for LSMI than the normal groups (HRs = 1.21, 95% CIs = 1.05–1.40). The LSMI groups also showed a higher HRs with 95% CIs for NAFLD than normal groups (HRs = 1.56, 95% CIs = 1.38–1.78). Participants with NAFLD had consistently less skeletal muscle mass over 12 years of follow-up. In conclusion, LSMI and NAFLD showed a relationship. Maintaining muscle mass should be emphasized in the management of NAFLD.

Abstract 007: Nonalcoholic Fatty Liver Disease and Subclinical Atherosclerosis: Analyses from the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Lisa B VanWagner ◽  
Christina M Shay ◽  
Hongyan Ning ◽  
John Wilkins ◽  
Cora E Lewis ◽  
...  
Keyword(s):  
Risk Factors ◽  
Young Adults ◽  
Liver Disease ◽  
Coronary Artery ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Fat ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Nonalcoholic Fatty Liver

Background: Nonalcoholic Fatty Liver Disease (NAFLD) and excess visceral adipose tissue (VAT) are associated with cardiovascular disease (CVD). Recent studies suggest that NAFLD and coronary artery calcification (CAC) are related independent of VAT. In a population-based cross-sectional sample of black and white adults free from prevalent liver or heart disease, we tested the hypothesis that NAFLD is associated with the presence of CAC and abdominal aortoiliac calcification (AAC) independent of VAT and other CVD risk factors. Methods: Participants from the Coronary Artery Risk Development in Young Adults study (Y25 exam) with concurrent computed tomography quantification of liver fat, CAC and AAC were included (n=2,163). NAFLD was defined as liver attenuation ≤ 40 Hounsfield Units after exclusion of other causes of liver fat (medication/alcohol use). Using the Agatston method, CAC/AAC presence was defined as a score > 0. Logistic regression models were used to calculate odds ratios and 95% confidence intervals. Results: Participant age was 49.9 (3.7) years and the sample was equally distributed by sex (55.6% female) and race (50.1% black). Mean BMI was 30.6 (7.1). The CAC and AAC prevalence was 26.5% and 49.6%. NAFLD prevalence was 9.6%. NAFLD participants were 50.1 (3.7) years old and more likely to be male (59.8% vs. 51.7%, p<0.0001), white (56.5% vs. 49.3%, p<0.05) and have the metabolic syndrome (70.1% vs. 22.6%, p<0.0001) than those with no NAFLD. They were also more likely to have CAC (37.2%) and AAC (60.9%) than those with no NAFLD (25.4% and 49.4%, respectively). In multivariable analyses adjusted for demographics and health behaviors, NAFLD was associated with the presence of CAC and AAC (Table 1). This association was attenuated after adjustment for CVD risk factors and VAT. Effect modification by race and sex was not statistically significant. Conclusion: In contrast to prior studies, our results suggest that the relationship between NAFLD and subclinical CVD is mediated by the presence of other CVD risk factors.

Molecular mechanisms of non-alcoholic fatty liver disease development

2021 ◽  
Vol 24 (4) ◽  
pp. 120
Author(s):  
T.S. Sall ◽  
E.S. Shcherbakova ◽  
S.I. Sitkin ◽  
T.Ya. Vakhitov ◽  
I.G. Bakulin ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Disease Development ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

scholarly journals Predicting and elucidating the etiology of fatty liver disease using a machine learning-based approach: an IMI DIRECT study

2020 ◽  
Author(s):  
Naeimeh Atabaki-Pasdar ◽  
Mattias Ohlsson ◽  
Ana Viñuela ◽  
Francesca Frau ◽  
Hugo Pomares-Millan ◽  
...  
Keyword(s):  
Machine Learning ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Prediction Models ◽  
Cell Function ◽  
Area Under The Curve ◽  
Liver Fat ◽  
Irreversible Damage ◽  
Alcoholic Fatty Liver

ABSTRACTBackgroundNon-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes serious health complications in type 2 diabetes (T2D) and beyond. Early diagnosis of NAFLD is important, as this can help prevent irreversible damage to the liver and ultimately hepatocellular carcinomas.Methods and FindingsUtilizing the baseline data from the IMI DIRECT participants (n=1514) we sought to expand etiological understanding and develop a diagnostic tool for NAFLD using machine learning. Multi-omic (genetic, transcriptomic, proteomic, and metabolomic) and clinical (liver enzymes and other serological biomarkers, anthropometry, and measures of beta-cell function, insulin sensitivity, and lifestyle) data comprised the key input variables. The models were trained on MRI image-derived liver fat content (<5% or ≥5%). We applied LASSO (least absolute shrinkage and selection operator) to select features from the different layers of omics data and Random Forest analysis to develop the models. The prediction models included clinical and omics variables separately or in combination. A model including all omics and clinical variables yielded a cross-validated receiver operator characteristic area under the curve (ROCAUC) of 0.84 (95% confidence interval (CI)=0.82, 0.86), which compared with a ROCAUC of 0.82 (95% CI=0.81, 0.83) for a model including nine clinically-accessible variables. The IMI DIRECT prediction models out-performed existing non-invasive NAFLD prediction tools.ConclusionsWe have developed clinically useful liver fat prediction models (see: www.predictliverfat.org) and identified biological features that appear to affect liver fat accumulation.

scholarly journals A Role for Gut Microbiome Fermentative Pathways in Fatty Liver Disease Progression

2020 ◽  
Vol 9 (5) ◽  
pp. 1369 ◽  
Author(s):  
Paula Iruzubieta ◽  
Juan M. Medina ◽  
Raúl Fernández-López ◽  
Javier Crespo ◽  
Fernando de la Cruz
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Disease Progression ◽  
Gut Microbiome ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Alcohol Fermentation ◽  
Alcoholic Fatty Liver ◽  
Liver Disease Progression ◽  
The Impact

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease in which environmental and genetic factors are involved. Although the molecular mechanisms involved in NAFLD onset and progression are not completely understood, the gut microbiome (GM) is thought to play a key role in the process, influencing multiple physiological functions. GM alterations in diversity and composition directly impact disease states with an inflammatory course, such as non-alcoholic steatohepatitis (NASH). However, how the GM influences liver disease susceptibility is largely unknown. Similarly, the impact of strategies targeting the GM for the treatment of NASH remains to be evaluated. This review provides a broad insight into the role of gut microbiota in NASH pathogenesis, as a diagnostic tool, and as a therapeutic target in this liver disease. We highlight the idea that the balance in metabolic fermentations can be key in maintaining liver homeostasis. We propose that an overabundance of alcohol-fermentation pathways in the GM may outcompete healthier, acid-producing members of the microbiota. In this way, GM ecology may precipitate a self-sustaining vicious cycle, boosting liver disease progression.

scholarly journals Coffee prevents fatty liver disease induced by a high-fat diet by modulating pathways of the gut–liver axis

2019 ◽  
Vol 8 ◽  
Author(s):  
Paola Vitaglione ◽  
Giovanna Mazzone ◽  
Vincenzo Lembo ◽  
Giuseppe D'Argenio ◽  
Antonella Rossi ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Coffee Consumption ◽  
Liver Fat ◽  
Standard Diet ◽  
High Fat ◽  
Metabolic Derangement ◽  
Alcoholic Fatty Liver

AbstractCoffee consumption is inversely associated with the risk of non-alcoholic fatty liver disease (NAFLD). A gap in the literature still exists concerning the intestinal mechanisms that are involved in the protective effect of coffee consumption towards NAFLD. In this study, twenty-four C57BL/6J mice were divided into three groups each receiving a standard diet, a high-fat diet (HFD) or an HFD plus decaffeinated coffee (HFD+COFFEE) for 12 weeks. Coffee supplementation reduced HFD-induced liver macrovesicular steatosis (P < 0·01) and serum cholesterol (P < 0·001), alanine aminotransferase and glucose (P < 0·05). Accordingly, liver PPAR- α (P < 0·05) and acyl-CoA oxidase-1 (P < 0·05) as well as duodenal ATP-binding cassette (ABC) subfamily A1 (ABCA1) and subfamily G1 (ABCG1) (P < 0·05) mRNA expressions increased with coffee consumption. Compared with HFD animals, HFD+COFFEE mice had more undigested lipids in the caecal content and higher free fatty acid receptor-1 mRNA expression in the duodenum and colon. Furthermore, they showed an up-regulation of duodenal and colonic zonulin-1 (P < 0·05), duodenal claudin (P < 0·05) and duodenal peptide YY (P < 0·05) mRNA as well as a higher abundance of Alcaligenaceae in the faeces (P < 0·05). HFD+COFFEE mice had an energy intake comparable with HFD-fed mice but starting from the eighth intervention week they gained significantly less weight over time. Data altogether showed that coffee supplementation prevented HFD-induced NAFLD in mice by reducing hepatic fat deposition and metabolic derangement through modification of pathways underpinning liver fat oxidation, intestinal cholesterol efflux, energy metabolism and gut permeability. The hepatic and metabolic benefits induced by coffee were accompanied by changes in the gut microbiota.

scholarly journals Murine models provide insight to the development of non-alcoholic fatty liver disease

2015 ◽  
Vol 28 (2) ◽  
pp. 133-142 ◽  
Author(s):  
D. T. Reid ◽  
B. Eksteen
Keyword(s):  
Animal Model ◽  
Liver Disease ◽  
Animal Models ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Treatment Strategies ◽  
Alcoholic Fatty Liver ◽  
Advantages And Disadvantages ◽  
The Metabolic Syndrome ◽  
Alcoholic Fatty Liver Disease

AbstractAssociated with the obesity epidemic, non-alcoholic fatty liver disease (NAFLD) has become the leading liver disease in North America. Approximately 30 % of patients with NAFLD may develop non-alcoholic steatohepatitis (NASH) that can lead to cirrhosis and hepatocellular carcinoma (HCC). Frequently animal models are used to help identify underlying factors contributing to NAFLD including insulin resistance, dysregulated lipid metabolism and mitochondrial stress. However, studying the inflammatory, progressive nature of NASH in the context of obesity has proven to be a challenge in mice. Although the development of effective treatment strategies for NAFLD and NASH is gaining momentum, the field is hindered by a lack of a concise animal model that reflects the development of liver disease during obesity and the metabolic syndrome. Therefore, selecting an animal model to study NAFLD or NASH must be done carefully to ensure the optimal application. The most widely used animal models have been reviewed highlighting their advantages and disadvantages to studying NAFLD and NASH specifically in the context of obesity.

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