Fatty Liver A Novel Component of the Metabolic Syndrome

Department of Medicine, Division of Diabetes, University of Helsinki, Finland, FIN-00029 HUCH, Helsinki, Finland.
Arteriosclerosis Thrombosis and Vascular Biology (Impact Factor: 6). 02/2008; 28(1):27-38. DOI: 10.1161/ATVBAHA.107.147538
Source: PubMed

ABSTRACT Although the epidemic of obesity has been accompanied by an increase in the prevalence of the metabolic syndrome, not all obese develop the syndrome and even lean individuals can be insulin resistant. Both lean and obese insulin resistant individuals have an excess of fat in the liver which is not attributable to alcohol or other known causes of liver disease, a condition defined as nonalcoholic fatty liver disease (NAFLD) by gastroenterologists. The fatty liver is insulin resistant. Liver fat is highly significantly and linearly correlated with all components of the metabolic syndrome independent of obesity. Overproduction of glucose, VLDL, CRP, and coagulation factors by the fatty liver could contribute to the excess risk of cardiovascular disease associated with the metabolic syndrome and NAFLD. Both of the latter conditions also increase the risk of type 2 diabetes and advanced liver disease. The reason why some deposit fat in the liver whereas others do not is poorly understood. Individuals with a fatty liver are more likely to have excess intraabdominal fat and inflammatory changes in adipose tissue. Intervention studies have shown that liver fat can be decreased by weight loss, PPARgamma agonists, and insulin therapy.

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    • "Simple steatosis, or fatty liver, occurs early in NAFLD and may progress to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis with increased risk of hepatocellular carcinoma [5] [6] [7]. NAFLD is strongly associated with obesity, insulin resistance, hypertension, and dyslipidemia and is now regarded as the liver manifestation of the metabolic syndrome (MetS) [8] [9] [10], a highly atherogenic condition even at a very early age [11] [12] [13]. When compared to control subjects who do not have hepatic steatosis, patients with NAFLD have a higher prevalence of atherosclerosis, as shown by increased carotid wall intimal thickness, increased numbers of atherosclerotic plaques, and increased plasma markers of endothelial dysfunction, which are independent of obesity and other established risk factors [13] [14] [15] [16] [17] [18] [19]. "
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    ABSTRACT: In the last 20 years, nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide, primarily as a result of the epidemic of obesity. NAFLD is strongly associated with insulin resistance, glucose intolerance, and dyslipidemia and is currently regarded as the liver manifestation of the metabolic syndrome, a highly atherogenic condition even at a very early age. Patients with NAFLD including pediatric subjects have a higher prevalence of subclinical atherosclerosis, as shown by impaired flow-mediated vasodilation, increased carotid artery intima-media thickness, and arterial stiffness, which are independent of obesity and other established risk factors. More recent work has identified NAFLD as a risk factor not only for premature coronary heart disease and cardiovascular events, but also for early subclinical abnormalities in myocardial structure and function. Thus, we conducted a systematic review and meta-analysis to test the hypothesis that NAFLD is associated with evidence of subclinical cardiac structural and functional abnormalities.
    08/2015; 2015:213737. DOI:10.1155/2015/213737
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    • "Thus, a strong bidirectional association between NAFLD and MetS has been proposed . Insulin resistance, the key feature of MetS, is considered to play a central role in the first stages of fatty liver infiltration [13] [14] [15]. However, whether insulin resistance and hyperinsulinemia are components of MetS promoting fatty liver or whether NAFLD itself induces chronic hyperinsulinemia by impaired insulin degradation is still under debate. "
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    ABSTRACT: Background & aims: Non-alcoholic fatty liver disease was traditionally interpreted as a condition which may progress to liver-related complications. However, the increased mortality is primarily a result of cardiovascular diseases. It has been suggested that fatty liver can be considered as the hepatic consequence of the metabolic syndrome. The aim was to describe the different clinical presentations of non-alcoholic fatty liver disease on the basis of the patatin-like phospholipase domain-containing protein3 (PNPLA3) rs738409 gene variant. Methods: Fatty liver was defined by ultrasonographic Hamaguchi's criteria in 211 consecutive subjects with non-alcoholic fatty liver disease. The rs738409 polymorphism was determined by TaqMan assays. Metabolic syndrome was defined according to ATPIII modified criteria. Results: Prevalence of PNPLA3-148II, PNPLA3-148IM, and PNPLA3-148MM genotypes was 45.0%, 40.7%, and 14.3% respectively. Prevalence of metabolic syndrome progressively increased with the severity of liver steatosis (from 52.5% to 65.2%, and 82.3% respectively, p<0.01). The PNPLA3-148MM group had significantly lower mean serum triglycerides (p<0.001), Framingham cardiovascular risk score (p<0.01) and lower prevalence of metabolic syndrome (p<0.05) and its components. Age and HOMA-IR were positive independent predictors of metabolic syndrome, while a negative independent association was found between metabolic syndrome and the homozygotes PNPLA3 I148M variant. Conclusions: We suggest a lower prevalence of MetS and reduced cardiovascular risk in NAFLD patients with PNPLA3MM genotype.
    European Journal of Internal Medicine 06/2014; 25(6). DOI:10.1016/j.ejim.2014.05.012 · 2.89 Impact Factor
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    • "Non-alcoholic fatty liver disease (NAFLD) is common in the general population, and it occurs even more frequently in patients with metabolic syndrome [1], [2]. Patients with NAFLD have an increased risk of cardiovascular disease (CVD) [2], [3] because these diseases share several risk factors and surrogate markers [3], [4]. In addition, NAFLD is often associated with atherosclerotic signs including the presence of carotid plaques [5] and coronary arterial calcium [6]. "
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    ABSTRACT: Although triglyceride accumulation in the liver causes non-alcoholic fatty liver disease (NAFLD), hypercholesterolemia is also a main cause of NAFLD as well as atherosclerosis. However, NAFLD and atherosclerosis have not been investigated simultaneously in animal models fed a high-cholesterol diet. Moreover, it is unclear whether systemic inflammation can exacerbate both pathologies in the same model. Accordingly, this study investigated the effect of additional systemic inflammation on NAFLD and atherosclerosis induced by cholesterol overload in wild animals. New Zealand white rabbits were divided into 4 groups: groups I (control) and II received normal chow, and groups III and IV received a 1% cholesterol diet. To induce inflammation via toll-like receptor (TLR)-4 signaling, groups II and IV received subcutaneous injections of 0.5 mL of 1% carrageenan every 3 weeks. After 3 months, total cholesterol markedly increased in groups III and IV, and the serum expressions of systemic inflammatory markers were elevated in the groups II-IV. Early NAFLD lesions (e.g., mild fatty changes in the liver with sporadic fibrosis) and atherosclerosis (e.g., intimal hyperplasia composed of foam cells) were observed in both the liver and aorta specimens from group III, and advanced lesions were observed in group IV. The expressions of inflammatory cellular receptors, TLR-2 and TLR-4, in the aorta gradually increased from group I to IV but were similar in the liver in groups II-IV. Cholesteryl ester (CE) levels were higher in group IV than in group III, although the difference was not significant. CE levels in the aorta were similar between groups III and IV. Systemic inflammation can simultaneously exacerbate existing early lesions due to cholesterol overload in both the liver and aorta of rabbits. However, the cellular response of inflammatory receptors and expression of cholesterol metabolites differ between these organs.
    PLoS ONE 06/2014; 9(6):e97841. DOI:10.1371/journal.pone.0097841 · 3.23 Impact Factor
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