Non-alcoholic steatohepatitis and metabolic syndrome

Unidade de Nutrição e Metabolismo, Departamento de Gastrenterologia, Instituto de Medicina Molecular, Hospital de Santa Maria, Lisbon, Portugal.
Current Opinion in Clinical Nutrition and Metabolic Care (Impact Factor: 3.99). 10/2006; 9(5):637-42. DOI: 10.1097/01.mco.0000241677.40170.17
Source: PubMed


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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    • "Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in the Western countries, considered the hepatic manifestation of the metabolic syndrome [1]. "
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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; 59(5):879-893. DOI:10.1002/mnfr.201400913 · 4.60 Impact Factor
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    • "Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in the Western countries, considered the hepatic manifestation of the metabolic syndrome [1]. "

    Molecular Nutrition & Food Research 01/2015; doi: 10.1002/mnfr.201400913. · 4.60 Impact Factor
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    • "In recent years, non-alcoholic fatty liver disease (NAFLD) has emerged as the leading liver disease in North America (Ong and Younossi 2007). NAFLD is defined by the accumulation of lipids in hepatocytes, and is prevalent in individuals with metabolic abnormalities associated with Metabolic Syndrome (MetS) (Machado and Cortez-Pinto 2006). According to the commonly cited " 2 hit hypothesis " of NAFLD progression (Day and James 1998), in the presence of a metabolic " second hit " in the form of oxidative stress, simple steatosis can progress into more severe forms of liver disease characterized by inflammation, fibrosis, and cell necrosis. "
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    ABSTRACT: Alpha-linolenic acid's (ALA) biological activity is poorly understood and primarily associated with its conversion to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Delta-6 desaturase (D6D) initiates the metabolism of linoleic acid (LA) and ALA to arachidonic acid, EPA, and DHA, respectively. In this study, D6D knock-out (D6KO) mice were used to evaluate the effects of ALA-rich oils in preventing hepatic steatosis and inflammation. D6KO and wild-type mice were fed 1 of 4 high-fat (14% w/w) diets: (i) lard (LD, 0% n-3 PUFA), (ii) canola oil + ARASCO (CD, 8% ALA), (iii) flax seed oil + ARASCO (FD, 55% ALA), (iv) menhaden oil (MD, 30% EPA/DHA) for 8 or 20 weeks. Livers of D6KO mice consuming CD and FD were depleted of EPA/DHA, and enriched in ALA. Markers of fat accumulation and inflammation were lowest in the MD-fed mice, at 8 and 20 weeks, regardless of genotype. CD- and FD-fed D6KO groups were found to have lower liver lipid accumulation and lower hepatic inflammation relative to the LD-fed mice at 8 weeks. In conclusion, while MD was the most protective, this study shows that ALA can act independently on risk factors associated with the development of fatty liver disease.
    Canadian Journal of Physiology and Pharmacology 06/2013; 91(6):469-79. DOI:10.1139/cjpp-2012-0308 · 1.77 Impact Factor
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