Buenos Aires, Argentina
Buenos Aires, Argentina

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Steinhardt A.P.,CONICET | Aranguren F.,University of Buenos Aires | Tellechea M.L.,Laboratory of Molecular Biology | Gomez Rosso L.A.,Laboratory of Lipids and Lipoproteins | And 7 more authors.
Metabolism: Clinical and Experimental | Year: 2010

Toll-like receptor 4 (TLR4) plays a key role in the activation of innate immune responses. Loss-of-function mutations in TLR4 prevent diet-induced obesity and insulin resistance (IR). We conducted a population cross-sectional study to evaluate whether Asp299Gly (rs4986790) TLR4 gene polymorphism is associated with metabolic syndrome (MS), surrogates of IR, and syndromes of lipid accumulation (SLAs) in Argentinean healthy male subjects. rs4986790 was genotyped in 621 healthy unrelated male blood donors. National Cholesterol Education Program/Adult Treatment Panel III-MS (NCEP/ATP III-MS); SLAs such as enlarged waist elevated triglyceride syndrome (EWET), hypertriglyceridemic waist (HW), and overweight-lipid syndrome (OLS); and surrogates of IR were assessed. The prevalence of MS, OLS, and EWET was significantly higher among Asp299Asp carriers (P < .05). These findings were confirmed using 32 000 bootstrap samples. Surrogate markers of IR were also significantly higher in Asp299Asp carriers (P < .05). Most findings were especially strengthened among individuals with C-reactive protein below the 95th percentile and/or total cholesterol to high-density lipoprotein cholesterol ratio ≥5. This is the first report to find, in Argentinean healthy male blood donors, associations between the Asp299Asp genotype of rs4986790 TLR4 gene polymorphism and high risk for NCEP/ATP III-MS, SLAs, and surrogates of IR. These findings are consistent with previous functional and observational studies showing that Asp299 allele, in comparison with Gly299, is associated with increased TLR4 activation, higher levels of inflammatory cytokines, acute-phase reactants and soluble adhesion molecules, and higher risk of atherosclerosis. © 2010 Elsevier Inc. All rights reserved.


Hirschler V.,Durand Hospital | Merono T.,Laboratory of Lipids and Lipoproteins | Maccallini G.,Durand Hospital | Rosso L.G.,Laboratory of Lipids and Lipoproteins | And 2 more authors.
Cardiovascular and Hematological Agents in Medicinal Chemistry | Year: 2011

Abstract: Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been proposed as a biomarker of risk of cardiovascular disease (CVD). Objective: To determine the association between Lp-PLA2 activity and BMI, insulin-resistance, components of the metabolic syndrome (MS), and lifestyle behaviors in healthy adolescent boys. Methods: Data were collected cross-sectionally from 164 adolescents from an amateur rugby club. BMI, blood pressure (BP), Tanner stages, glucose, insulin, lipids, and Lp-PLA2 activity were measured. Questionnaires for lifestyle behaviors were completed. Results: Approximately 26% of the adolescents were obese and 23% overweight. There was a univariate association between Lp-PLA2 and BMI (r=0.16;p=0.042), triglycerides (r=0.26;p=0.001), LDL-C (r=0.46;p<0.001), apo B (r=0.55;p<0.001), whereas waist circumference, BP, glucose, HOMA-IR, and HDL-C were not correlated. None of the lifestyle behaviors were significantly correlated with Lp-PLA2. In order to analyze Lp-PLA2 association with known CVD risk conditions, adolescents were categorized according to overweight/obesity and to the presence of metabolic syndrome. Conversely, as it was for LDL-C and apo B concentration, Lp-PLA2 activity was not higher in adolescents with obesity. Multiple regression analysis showed that apo B was significantly associated with Lp-PLA2 adjusted for age, BMI, triglyc-erides and LDL-C (R2=0.32). Conclusion: Lp-PLA2 activity was only associated with apo B adjusted for several confounding variables, suggesting that its clinical utility to identify individuals at risk for CVD does not surpass LDL-C and apo B in healthy adolescents. As plaque morphology may change with age, associations of Lp-PLA2 with CVD may likewise vary with age. © 2011 Bentham Science Publishers Ltd.


Merono T.,Laboratory of Lipids and Lipoproteins | Sorroche P.,Hospital Italiano Of Buenos Aires | Rosso L.A.G.,Laboratory of Lipids and Lipoproteins | Casanas L.,Hospital Italiano Of Buenos Aires | And 3 more authors.
Clinical Biochemistry | Year: 2010

Objective: To characterize the lipid-related atherogenic risk factors in iron deficiency anaemia (IDA) patients. Design and methods: Twenty IDA women were compared to healthy age-matched controls. Lipoprotein profile, cholesteryl ester transfer protein (CETP), paraoxonase (PON) 1 and lipoprotein-associated phospholipase A2 (LpPLA2) activities and plasma levels of oxidized-LDL were evaluated. Results: Triglycerides were higher (median [range]) (1.0 [0.5-1.9] vs. 0.7 [0.5-1.5] mmol/L, p < 0.05) and HDL-C lower (mean ± SD) (1.3 ± 0.3 vs. 1.6 ± 0.4 mmol/L, p < 0.01) in the patients group. CETP (197 ± 29% vs. 151 ± 29% mL- 1 h- 1, p < 0.001), PON 1 (122 ± 17 vs. 140 ± 33 μmol mL- 1 min- 1, p < 0.05) and LpPLA2 (9.6 ± 2.0 vs. 8.1 ± 1.7 μmol mL- 1 h- 1, p < 0.05) activities were different in IDA women. No difference was observed in oxidized-LDL. Haemoglobin correlated negatively with triglycerides (r = - 0.35, p < 0.05), CETP (r = - 0.62, p < 0.001) and LpPLA2 (r = - 0.34, p < 0.05), while ferritin was positively associated with HDL-C (r = 0.39, p < 0.05) and inversely with CETP (r = - 0.49, p < 0.005). Conclusion: The alterations in lipoprotein profile, CETP, PON 1 and LpPLA2 activities described in the present study indicate that non-treated IDA might represent a proatherogenic state. © 2009 The Canadian Society of Clinical Chemists.


Miksztowicz V.,Laboratory of Lipids and Lipoproteins | Siseles N.,University of Buenos Aires | MacHulsky N.F.,Laboratory of Lipids and Lipoproteins | Schreier L.,Laboratory of Lipids and Lipoproteins | Berg G.,University of Buenos Aires
Climacteric | Year: 2012

Background Metalloproteinases (MMPs) are synthesized in the subendothelium and are involved in the atherosclerosis and cardiovascular disease process because of their major significance in vascular remodeling and plaque rupture. MMPs are also synthesized in adipose tissue during angiogenesis; however, the role of these enzymes in obesity and insulin-resistant states is still controversial. Objective To evaluate MMP-2 activity in the circulation of overweight and obese women and in normal-weight controls, and to associate the levels of these factors with metabolic, adipose tissue and inflammation biomarkers. Methods Plasma MMP-2 activity, adiponectin and C-reactive protein concentration, lipoprotein profile and HOMA were determined in 39 healthy women (13 normal weight and 26 overweight/obese). Results Overweight/obese women were older (p <0.001) than normal-weight women; 20/26 of overweight/obese women were postmenopausal compared with 4/13 of normal-weight women. Overweight/obese women had significantly higher plasma activity of MMP-2 than controls (mean relative area: 0.81 (range 0.4-1.92) vs. 1.33 (range 0.4-;3.1); p <0.005); this difference was lost after adjusting for menopausal status. MMP-2 activity positively correlated with waist circumference (p <0.002), HOMA (p <0.003), and high-sensitivity C-reactive protein (p <0.05), apolipoprotein B (p =0.006) and triglyceride/high density lipoprotein (HDL) cholesterol index (p <0.001), and negatively with HDL cholesterol (p <0.001), HDL2 cholesterol (p <0.008), HDL3 cholesterol (p <0.05) and adiponectin (p <0.05). The association with HOMA and adiponectin persisted even after adjusting for menopausal status. Conclusion Our finding of increased plasma activity of MMP-2 in overweight/obese women, associated with menopausal status, is important given that it fits in with an early stage of cardiovascular disease; the association of MMP-2 activity with obesity markers may be a link between adipose tissue and risk for cardiovascular disease. © 2012 International Menopause Society.


Zago V.,Laboratory of Lipids and Lipoproteins | Lucero D.,Laboratory of Lipids and Lipoproteins | MacRi E.V.,University of Buenos Aires | Cacciagiu L.,Laboratory of Lipids and Lipoproteins | And 6 more authors.
Annals of Nutrition and Metabolism | Year: 2010

The close association between nonalcoholic fatty liver and insulin resistance is now widely recognized. While the former is characterized by excessive intrahepatic triglyceride accumulation, the latter induces overproduction of very-low-density lipoprotein (VLDL) particles. It has not been well elucidated whether these apparently opposite mechanisms impact on VLDL characteristics or not. The aim of the present study was to evaluate the VLDL secretion and features resulting from insulin resistance and fatty liver in rats fed a sucrose-rich diet (SRD, i.e. addition of sucrose to drinking water during 12 weeks). No differences in calorie intake were observed in comparison to controls. Both groups showed similar weight gains throughout the treatment period. However, SRD rats showed an increased proportion of body fat as assessed by X-ray absorptiometry, increased visceral obesity, liver weight and fat accumulation in the liver (p < 0.04). Histological study revealed moderate micro- and macrovesicular steatosis. Fasting insulin, triglyceride and free fatty acid (FFA) levels increased while VLDLs decreased in SRD rats (p < 0.05). The chemical composition of VLDLs of SRD rats showed a higher percentage of triglycerides, and the VLDL triglyceride/protein ratio, an estimator of lipoprotein size, suggests that VLDL particles of SRD rats are larger than those of controls (p < 0.0005). FFA levels correlated with VLDL triglycerides (r = 0.49, p = 0.03) and liver fat content correlated with plasma triglycerides (r = 0.65), VLDL triglycerides (r = 0.55) and triglyceride/protein ratio (r = 0.52, p < 0.02). The VLDL secretion rate assay showed an increase in SRD rats (p < 0.02), confirming an overproduction despite liver fat accumulation. Our findings are consistent with an insulin resistance development model in which hepatic lipid content would constitute an important determinant of a triglyceride-rich, large-particle VLDL secretion; both features would increase its atherogenic potential. Copyright © 2010 S. Karger AG, Basel.

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