Fatty liver - A novel component of the metabolic syndrome
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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ABSTRACT: In insulin-resistance, VLDL presents alterations that increase its atherogenic potential. The mechanism by which insulin-resistance promotes the production of altered VLDL is still not completely understood. The aim of this study was to evaluate the relationship between the expression of sterol regulatory element binding protein 1c (SREBP-1c) and of peroxisome proliferator-activated receptor-α (PPAR-α), with the features of composition and size of VLDL in an insulin-resistance rat model induced by a sucrose rich diet (SRD). The study was conducted on 12 male Wistar rats (180g) receiving SRD (12 weeks) and 12 controls. Lipid profile, free fatty acids, glucose, and insulin were measured. Lipid content in liver and visceral fat were assessed. Isolated VLDL (d<1.006g/ml) was characterized by its chemical composition and size by HPLC. The respective hepatic expression of SREBP-1c and PPAR-α was determined (Western blot). As expected, SRD had elevated triglycerides (TG), free fatty acids and insulin levels, and decreased HDL-cholesterol (p<0.05), together with augmented hepatic and visceral fat (p<0.05). SRD showed higher VLDL total mass - with increased TG content - and predominance of large VLDL (p<0.05). SRD showed an increase in SREBP-1c (precursor and mature forms) and decreased PPAR-α expression (p<0.045). SREBP-1c forms were positively associated with VLDL total mass (p<0.04), VLDL-TG% (p<0.019), and large VLDL% (p<0.002). On the other hand, PPAR-α correlated negatively with VLDL total mass (p=0.05), VLDL-TG% (p=0.005), and large VLDL% (p=0.002). Insulin-resistance, by coordinated activation of SREBP-1c and reduction of PPAR-α, could promote the secretion of larger and TG over-enriched VLDL particles, with greater atherogenic capacity. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.Clinica e Investigacion en Arteriosclerosis 03/2015; DOI:10.1016/j.arteri.2014.11.002
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ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and a risk factor for both cardiovascular and hepatic related morbidity and mortality. The increasing prevalence of this disease requires novel therapeutic approaches to prevent disease progression. Farnesoid X receptors are bile acid receptors with roles in lipid, glucose, and energy homeostasis. Synthetic farnesoid X receptor (FXR) agonists have been developed to specifically target these receptors for therapeutic use in NAFLD patients. Here, we present a review of bile acid physiology and how agonism of FXR receptors has been examined in pre-clinical and clinical NAFLD. Early evidence suggests a potential role for synthetic FXR agonists in the management of NAFLD; however, additional studies are needed to clarify their effects on lipid and glucose parameters in humans.Current Atherosclerosis Reports 04/2015; 17(4):500. DOI:10.1007/s11883-015-0500-2 · 3.06 Impact Factor
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ABSTRACT: The hypothesis that treatment with phytosterols in patients with nonalcoholic fatty liver disease (NAFLD) may increase circulating endothelial progenitor cells (EPCs) levels was tested in the study. Forty patients with an abdominal ultrasonographic diagnosis of NAFLD were randomly assigned to phytosterols powder treatment at 1.8 g/day for 4 weeks (n = 20) or a control group, with crossover to the alternate therapy for another 4 weeks after a 2-week wash-out period. Flow cytometry with quantification of EPC markers in peripheral blood samples was used to assess circulating EPC levels. Phytosterols treatment significantly decreased levels of low-density lipoproteins, fasting glucose, and hemoglobin-A1C. Treatment with phytosterols in patients with NAFLD markedly suppressed high sensitivity C-reactive protein concentrations, and enhanced superoxide dismutase, as compared to baseline. We also showed that administration of phytosterols significantly increased the insulin-like growth factor-1 concentrations (change from baseline of 22.47%, P < 0.0001; 18.49%, P = 0.0002). Moreover, intake of phytosterols significantly enhanced circulating EPC levels (CD34+, CD34+KDR+, CD34+KDR+CD133+, all P < 0.05) in NAFLD patients. Taken together, 4-week treatment with phytosterols in NAFLD patients significantly increased circulating EPC levels, and these findings provide a new strategy in treating patients with NAFLD.