Non-alcoholic steatohepatitis and metabolic syndrome.
ABSTRACT Non-alcoholic steatohepatitis is part of a disease spectrum, non-alcoholic fatty liver disease, ranging from simple steatosis to cirrhosis, which is the most frequent cause of abnormal liver tests. There is clinical and epidemiological evidence that non-alcoholic fatty liver disease is the hepatic manifestation of the metabolic syndrome, having in common insulin resistance.
The interest in the metabolic syndrome concept has been questioned. Insulin resistance, oxidative stress, mitochondrial dysfunction, immune deregulation and adipokines seem to be crucial in the pathogenesis of non-alcoholic fatty liver disease. The main treatment continues to rely on lifestyle changes, including weight loss strategies. Bariatric surgery in morbidly obese patients and insulin-sensitizing agents seem to be beneficial.
There is strong evidence of the association of non-alcoholic steatohepatitis with the features of the metabolic syndrome, with its increased cardiovascular risk. Population interventions in order to change lifestyles and diet patterns that constitute risk factors for both situations are urgently needed. There is, however, evidence that in the presence of other risk factors, insulin resistance may be less important. These secondary forms of non-alcoholic steatohepatitis must be recognized, as they are potentially treatable by withdrawing the steatogenic factor.
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ABSTRACT: Roles of alcohol consumption in nonalcoholic fatty liver disease are still controversial, although several cross-sectional studies have suggested the beneficial effect of light to moderate drinking on fatty liver. We analyzed the longitudinal relationship between drinking pattern and fatty liver. We included 5297 Japanese individuals (3773 men and 1524 women) who underwent a baseline study in 2003 and follow-up at least once from 2004 to 2006. Generalized estimating equation was used to estimate any association between drinking pattern and fatty liver assessed by ultrasonography. At baseline, 1179 men (31.2%) and 235 women (15.4%) had fatty liver; 2802 men (74.2%) and 436 women (28.6%) reported alcohol consumption. At the latest follow-up, 348 of 2594 men (13.4%) and 101 of 1289 women (7.8%) had newly developed fatty liver; 285 of 1179 men (24.2%) and 70 of 235 women (29.8%) demonstrated a remission of fatty liver. In men, drinking 0.1-69.9 g/week (odds ratio, 0.79 [95% confidence interval, 0.68-0.90]), drinking 70.0-139.9 g/week (0.73 [0.63-0.84]), drinking 140.0-279.9 g/week (0.69 [0.60-0.79]), and drinking ⩾280.0 g/week (0.68 [0.58-0.79]) were inversely associated with fatty liver after adjusting for obesity, exercise, and smoking. In women, drinking 0.1-69.9 g/week (0.71 [0.52-0.96]) and drinking 70.0-139.9 g/week (0.67 [0.45-0.98]) were inversely associated with fatty liver after the adjustment. Light to moderate alcohol consumption, or even somewhat excessive amounts especially in men, was likely to protect most individuals against fatty liver over time. Copyright © 2014. Published by Elsevier B.V.Journal of Hepatology 11/2014; DOI:10.1016/j.jhep.2014.11.025 · 10.40 Impact Factor
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ABSTRACT: Flavonoids and related compounds seem to have favorable effects on non-alcoholic fatty liver disease (NAFLD) progression, although the exact mechanisms implicated are poorly understood. In this study, we aimed to investigate the effect of the flanovol quercetin on gene expression deregulation involved in the development of NAFLD, as well as the possible implication of phosphatidylinositol 3-kinase (PI3K)/AKT pathway modulation. We used an in vivo model based on methionine and choline deficient (MCD) diet-fed mice and an in vitro model consisting of Huh7 cells incubated with MCD medium. MCD-fed mice showed classical pathophysiological characteristics of non-alcoholic steatohepatitis (NASH), associated with altered transcriptional regulation of fatty acid uptake- and trafficking-related gene expression, with increased lipoperoxidation. PI3K/AKT pathway was activated by MCD and triggered gene deregulation causing either activation or inhibition of all studied genes as demonstrated through cell incubation with the PI3K inhibitor LY294002. Treatment with quercetin reduced AKT phosphorylation and oxidative/nitrosative stress, inflammation and lipid metabolism-related genes displayed a tendency to normalize in both in vivo and in vitro models. These results place quercetin as a potential therapeutic strategy for preventing NAFLD progression by attenuating gene expression deregulation, at least in part through PI3K/AKT pathway inactivation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Molecular Nutrition & Food Research 02/2015; DOI:10.1002/mnfr.201400913 · 4.91 Impact Factor
Molecular Nutrition & Food Research 01/2015; doi: 10.1002/mnfr.201400913. · 4.91 Impact Factor