Weight loss is associated with improved endothelial dysfunction via NOX2-generated oxidative stress down-regulation in patients with the metabolic syndrome

Abstract

The aim of this study was to assess whether adherence to a restricted-calorie, Mediterranean-type diet improves endothelial dysfunction and markers of oxidative stress in patients with metabolic syndrome. A moderately low-calorie (600 calories/day negative energy balance), low-fat, high-carbohydrate diet (<30% energy from fat, <10% from saturated fat and 55% from carbohydrate) was prescribed to 53 outpatients with the metabolic syndrome. Participants were divided into two groups according to body weight loss > or < 5% after 6 months. Group A (n = 23) showed a remarkable decrease in body weight (-6.8%), body-mass-index (-4.6%), waist circumference (-4.8%), HOMA-IR (-27.2%), plasma glucose, glycosylated haemoglobin, total and LDL-cholesterol, blood pressure, serum NOX2 (the catalytic core of NADPH oxidase) (-22.2%) and urinary8-isoprostanes (-39.0%) and an increase of serum NOx (Nitrite/Nitrate) (+116.8%) and adiponectine (+125.5%) as compared with those in group B (n = 30). A statistically significant increase in brachial artery flow-mediated dilatation was observed in group A (+24.7%; p < 0.001), while no changes were present in group B. Variations of flow-mediated dilatation were statistically and negatively correlated with changes of serum NOX2 levels (p = 0.04), body-mass-index (p < 0.01), waist circumference (0.01), glycosylated haemoglobin (p < 0.01), LDL-cholesterol (p < 0.01) and triglycerides (p < 0.05) and positively correlated with changes of serum NOx (p < 0.001) and adiponectin (p = 0.01). The results show that moderate weight loss is able to improve endothelial dysfunction in patients with the metabolic syndrome. The coexistent decrease of NOX2 activation suggests a role for oxidative stress in eliciting artery dysfunction.

Adiponectin as a Link Between Type 2 Diabetes and Vascular NADPH Oxidase Activity in the Human Arterial Wall: The Regulatory Role of Perivascular Adipose Tissue

“…Given that type 2 diabetes is associated with increased activity of NADPH oxidase in experimental models (28,29) and the vascular wall (26,30), hypoadiponectinemia (a key feature in obesity and type 2 diabetes) (7) might be a link between type 2 diabetes and vascular disease pathogenesis. At a clinical level, adiponectin released by PVAT exerts vasodilatory effects on human microvessels (31), while weight loss leading to increased adiponectin levels at the same time improves endothelial function and reduces serum NOX2 levels (32). We have recently shown that adiponectin affects the vascular redox state by regulating eNOS coupling in the vascular endothelium (15), but it is unclear how a large molecule like adiponectin that is released from PVAT can reach the vascular endothelium and exert a paracrine effect.…”

Clinical Application of NOX Activity and Other Oxidative Biomarkers in Cardiovascular Disease: A Critical Review

“…Increased values of F2-IsoP have been detected in patients with different risk factors of atherosclerosis such as hypertension, diabetes, dyslipidemia, smoking, obesity, and metabolic syndrome (3,29,59,84,86). Interventional studies demonstrated that the modulation of risk factors resulted in changes of F2-IsoP values.…”

Oxidative stress: New insights on the association of non-alcoholic fatty liver disease and atherosclerosis

“…Accordingly, we demonstrated that patients with genetically determined low oxidative stress, disclosed impaired formation of urinary 8-iso-PGF2α [63] . Increased values of urinary 8-iso-PGF2α and serum sNOX2-dp levels have been detected also in subjects with cardiovascular risk factors such as hypertension, diabetes, dyslipidemia, obesity, sleep apnoea syndrome, atrial fibrillation and MetS [66][67][68][69][70][71] , which are all commonly present in patients with NAFLD.…”

“…Impaired FMD has been found in several CV and metabolic diseases related to chronic low-grade inflammation and oxidative stress [67,69,75,[81][82][83][84] . Improvement of FMD with a coexistent decrease of NOX2 activation has been observed in patients with MetS after moderate weight loss [69] . Impaired endothelial function was suggested also in NAFLD subjects [31,85] .…”