endothelin-1 and Overweight

To determine whether postprandial metabolic and vascular responses induced by a high-fat and high-carbohydrate meal are attenuated by ingestion of the flavonol quercetin.. Twenty-two overweight-to-obese hypertensive patients participated in a randomized, double-blind, controlled, crossover meal study. They consumed a test meal (challenge) rich in energy (4754 kJ), fat (61.6 g), saturated fatty acids (53 % of total fatty acids), and carbohydrates (113.3 g) with either placebo or 54 mg quercetin. Blood pressure, reactive hyperemia index (RHI), high-sensitive C-reactive protein (hs-CRP), soluble endothelial-derived adhesion molecules, parameters of lipid and glucose metabolism, and markers of antioxidant status were measured before the meal and at 2 and 4 h postprandially.. Systolic and diastolic blood pressure increased significantly over time, but were not affected by treatment (placebo or quercetin). During both treatments, serum endothelin-1, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and plasma asymmetric dimethylarginine slightly decreased over time, whereas RHI increased. Serum triglycerides, total cholesterol, and insulin significantly increased, whereas HDL cholesterol and glucose significantly decreased over time, again with no effect of treatment. Plasma α-tocopherol significantly increased, and plasma Trolox equivalent antioxidative capacity decreased over time. Serum hs-CRP, plasma retinol, and β-carotene did not significantly change during the trial.. In hypertensive patients, a high-energy meal did not lead to postprandial impairment of vascular endothelial function. Postprandial metabolic responses induced by the challenge, such as lipemia and insulinemia, were not attenuated by the concomitant ingestion of quercetin.. This trial was registered at www.germanctr.de/ and http://apps.who.int/trialsearch/ as DRKS00000555.

Topics: Adult; Aged; Arginine; beta Carotene; Blood Pressure; C-Reactive Protein; Cholesterol; Cross-Over Studies; Double-Blind Method; Endothelin-1; Female; Humans; Hypertension; Insulin; Intercellular Adhesion Molecule-1; Male; Middle Aged; Obesity; Onions; Overweight; Plant Extracts; Postprandial Period; Quercetin; Triglycerides; Vascular Cell Adhesion Molecule-1; Vitamin A

Previous studies of the health effects of low-fat milk or dairy consumption on the metabolic syndrome have yielded inconsistent results. The present study aimed to investigate the effects of low-fat milk consumption on traits associated with the metabolic syndrome, as well as inflammatory and atherogenic biomarkers, in Korean adults with the metabolic syndrome.. Overweight Koreans with the metabolic syndrome (n = 58) were recruited and randomly assigned to either the low-fat milk or control group. The low-fat milk group was instructed to consume two packs of low-fat milk per day (200 mL twice daily) for 6 weeks, and the control group was instructed to maintain their habitual diet. Clinical investigations were conducted during the screening visit, on study day 0, and after 6 weeks.. No significant differences in changes in body mass index, blood pressure, lipid profile and adiponectin levels, as well as levels of inflammatory markers, oxidative stress markers and atherogenic markers, were found between the low-fat milk and control groups. However, compared to the controls, significant favourable decreases in serum soluble vascular adhesion molecule-1 and endothelin-1 levels were found in the 12 subjects with high blood pressure and in the 18 subjects with hypertriglyceridaemia in the low-fat milk group.. The present study did not demonstrate an overall beneficial effect of low-fat milk consumption in subjects with the metabolic syndrome. However, low-fat milk consumption may have a favourable effect on atherogenic markers in subjects with high blood pressure or hypertriglyceridaemia.

Topics: Adult; Animals; Atherosclerosis; Biomarkers; Body Mass Index; Diet, Fat-Restricted; Endothelin-1; Follow-Up Studies; Humans; Hypertension; Hypertriglyceridemia; Inflammation Mediators; Insulin Resistance; Metabolic Syndrome; Middle Aged; Milk; Overweight; Oxidative Stress; Patient Dropouts; Republic of Korea; Risk Factors; Vascular Cell Adhesion Molecule-1

Obesity and increased arterial stiffness are independent risk factors for cardiovascular disease. Arterial stiffness is increased in obese individuals than in age-matched nonobese individuals. We demonstrated that dietary modification and exercise training are effective in reducing arterial stiffness in obese persons. However, the differences in the effect on arterial stiffness between dietary modification and exercise training are unknown. The purpose of the current study was to compare the effect of dietary modification and aerobic exercise training on arterial stiffness and endothelial function in overweight and obese persons. Forty-five overweight and obese men (48 ± 1 year) completed either a dietary modification (well-balanced nutrient, 1680 kcal/day) or an exercise-training program (walking, 40-60 min/day, 3 days/week) for 12 weeks. Before and after the intervention, all participants underwent anthropometric measurements. Arterial stiffness was measured based on carotid arterial compliance, brachial-ankle pulse wave velocity (baPWV), and endothelial function was determined by circulating level of endothelin-1 (ET-1) and nitric oxide metabolite (nitrites/nitrate as metabolite: NOx). Body mass and waist circumference significantly decreased after both intervention programs. Weight loss was greater after dietary modification than after exercise training (-10.1 ± 0.6 kg vs. -3.6 ± 0.5 kg, p < .01). Although arterial stiffness and the plasma levels of ET-1 and NOx were improved after dietary modification or exercise training, there were no differences in those improvements between the 2 types of interventions. Exercise training improves arterial function in obese men without as much weight loss as after dietary modification.

Topics: Adult; Body Mass Index; Cardiovascular Diseases; Diet Records; Diet, Reducing; Endothelin-1; Endothelium, Vascular; Exercise; Humans; Japan; Life Style; Male; Middle Aged; Nitric Oxide; Obesity; Overweight; Oxygen Consumption; Risk Factors; Vascular Stiffness; Waist Circumference; Walking; Weight Loss

The aim of this study was to investigate the relationship between endothelin-1, nitric oxide, insulin resistance, and blood pressure in young subjects with a high prevalence of excess weight and/or elevated blood pressure. In a cohort of 238 children (mean age = 11.1 years), height, weight, waist circumference, and blood pressure were assessed. Body mass index, waist-to-height ratio, and blood pressure percentiles were calculated, and the children were classified as having excess weight and elevated blood pressure according to the International Obesity Task Force and the US blood pressure nomograms specific for gender, age and height, respectively. Endothelin-1 and nitric oxide production were assessed, and the homeostatic model assessment index was calculated. Forty-three percent of children were male, 71% had excess weight, and 37% had systolic and/or diastolic values above the ninetieth percentile. Plasma endothelin-1 and nitric oxide production were independently correlated (p < 0.05). In multivariate analyses, the HOMA index was associated with systolic and diastolic blood pressure (p = 0.01), and nitric oxide was independently related to diastolic blood pressure (p = 0.04), even after adjustment for measures of body composition. By using the waist-to-height ratio instead of BMI in the statistical model, the association between the homeostatic model assessment index and blood pressure was attenuated, while the results remained similar for nitric oxide. No correlation was found between endothelin-1 and blood pressure. In our study population, the correlation between nitric oxide and blood pressure and the lack of a relationship between endothelin-1 and blood pressure could be explained by an increase in the vasodilator effect of local and systemic nitric oxide, which counteracts the possible hypertensive effect of endothelin-1.

Topics: Adolescent; Blood Pressure; Child; Cross-Sectional Studies; Endothelin-1; Female; Humans; Hypertension; Insulin Resistance; Male; Nitric Oxide; Overweight

Topics: Adiponectin; Adolescent; Adult; Biomarkers; Endothelin-1; Humans; Interleukin-6; Male; Middle Aged; Obesity; Overweight; Risk Factors; Young Adult

Weight loss improves endothelial function in overweight individuals. The effects of weight loss through combined aerobic and resistance training and caloric restriction on in vivo vascular measures and blood markers associated with the regulation of endothelial function have not been comprehensively examined. Therefore, we investigated brachial artery endothelial function and potential regulatory blood markers in twenty overweight women (30.3 ± 2.0 years) who participated in 16 weeks of aerobic (5 d/wk) and resistance training (2 d/wk) (combined: ≥ 250 kcal/d) and caloric restriction (-500 kcal/d versus requirement). Resting brachial artery flow mediated dilation (FMD) and circulating endothelin-1 (ET-1) and interleukin-6 (IL-6) were assessed at baseline and following the intervention. Relative and absolute FMD increased (before: 4.0 ± 0.5% versus after: 6.9 ± 0.6%, P < 0.05, and before: 0.14 ± 0.02 mm versus after: 0.23 ± 0.02 mm, P < 0.05, resp.), while body mass decreased (before: 86.9 ± 2.4 kg versus after: 81.1 ± 2.4 kg, P < 0.05) following the intervention. There were no changes in either blood marker (IL-6: before: 1.5 ± 0.2 pg/mL versus after: 1.5 ± 0.1 pg/mL, P > 0.05, and ET-1: before: 0.55 ± 0.05 pg/mL versus after: 0.59 ± 0.09 pg/mL, P > 0.05). 16 weeks of combined aerobic/resistance training and diet-induced weight loss improved endothelial function in overweight and obese young women, but this increase was not associated with changes in blood markers of vasoconstriction or inflammation.

Topics: Adult; Body Composition; Diet; Endothelin-1; Endothelium, Vascular; Energy Intake; Exercise Therapy; Female; Humans; Obesity; Overweight; Resistance Training; Weight Loss

To determine whether endothelin (ET)-1 vasoconstrictor tone is greater in overweight and obese adults with the metabolic syndrome (MetS).. Forty overweight/obese middle-aged and older adults (age: 43-71 years; BMI: 25.1-36.9 kg/m²) were studied: 20 without MetS (13 M/7 F) and 20 with MetS (13 M/7 F). MetS was established according to NCEP ATP III guidelines. Forearm blood flow (FBF; plethysmography) responses to intra-arterial infusion of selective ET(A) receptor blockade (BQ-123; 100 nmol/min; for 60 min) and non-selective ET(A/B) receptor blockade (BQ-123 + BQ-788 [50 nmol/min for 60 min]) were determined.. In response to the selective ET(A) antagonism, there was a significant increase in forearm blood flow from baseline in both groups. However, the increase in forearm blood flow was significantly higher (P=0.03; ~45%) in the overweight/obese group with MetS than the group without MetS. In contrast, there were no significant group differences in FBF responses to non-selective ET(A/B) receptor blockade. Peak vasodilator responses to nonselective ET(A/B) blockade were ~50% higher than baseline blood flow in the overweight/obese groups without and with MetS.. MetS is associated with higher ET-1 vasoconstrictor tone in overweight/obese adults. The enhanced ET-1 vasoconstrictor activity with MetS is mediated by the ET(A) receptor subtype.

Topics: Adult; Aged; Blood Vessels; Body Mass Index; Cross-Sectional Studies; Endothelin A Receptor Antagonists; Endothelin B Receptor Antagonists; Endothelin-1; Female; Forearm; Humans; Male; Metabolic Syndrome; Middle Aged; Obesity; Overweight; Prehypertension; Receptor, Endothelin A; Receptor, Endothelin B; Regional Blood Flow; Signal Transduction; Vasoconstriction; Vasodilation; Vasodilator Agents

The aim of the present study was to evaluate the potential association between dietary nutrients and alterations in DNA methylation in a set of five candidate genes, including CD14, Et-1, iNOS, HERV-w and TNFα, in a population of overweight/obese subjects. We evaluated possible associations between gene methylation and clinical blood parameters, including total cholesterol (TC), low- and high-density lipoprotein cholesterol (LDL-C and HDL-C), triglyceride and homocysteine levels. We employed validated methods to assess anthropometric, clinical and dietary data, as well as pyrosequencing to evaluate DNA methylation of the five candidate genes in 165 overweight/obese subjects. There was no association between body mass index and DNA methylation of the five candidate genes in this group of subjects. Positive associations were observed between TNFα methylation and blood levels of LDL-C (β = 0.447, p = 0.002), TC/HDL-C (β = 0.467, p = 0.001) and LDL-C/HDL-C (β = 0.445, p = 0.002), as well as between HERV-w methylation and dietary intakes of β-carotene (β = 0.088, p = 0.051) and carotenoids (β = 0.083, p = 0.029). TNFα methylation showed negative associations with dietary intakes of cholesterol (β = -0.278, p = 0.048), folic acid (β = -0.339, p = 0.012), β-carotene (β = -0.332, p = 0.045), carotenoids (β = -0.331, p = 0.015) and retinol (β = -0.360, p = 0.008). These results suggest a complex relationship among nutrient intake, oxidative stress and DNA methylation.

Topics: Adult; Aged; beta Carotene; Body Mass Index; Carotenoids; Cholesterol; Cholesterol, HDL; DNA Methylation; Eating; Endothelin-1; Energy Intake; Female; Folic Acid; Gene Products, env; Humans; Inflammation; Lipopolysaccharide Receptors; Lipoproteins, LDL; Male; Middle Aged; Nitric Oxide Synthase Type II; Nutritional Status; Obesity; Overweight; Pregnancy Proteins; Triglycerides; Tumor Necrosis Factor-alpha; Vitamin A

Pediatric obesity is associated with endothelial dysfunction and hypoadiponectinemia, but the relationship between these two conditions remains to be fully clarified. Whether enhanced release of endothelin-1 (ET-1) may directly impair adiponectin (Ad) production in obese children is not known.. The aim of the study was to explore whether and how high circulating levels of ET-1 may contribute to impair Ad production, release, and vascular activity.. Sixty children were included into obese (Ob; n = 30), overweight (OW; n = 11), and lean (n = 19) groups. Total and high-molecular-weight Ad, ET-1, vascular cell adhesion molecule-1, and von Willebrand factor levels were measured in serum samples. Adipocytes were stimulated with exogenous ET-1 or with sera from lean, OW, and Ob, and Ad production and release measured in the absence or in the presence of ETA (BQ-123) and ETB (BQ-788) receptor blockers, p42/44 MAPK inhibitor PD-98059, or c-Jun NH2-terminal protein kinase inhibitor SP-600125. Vasodilation to Ad was evaluated in rat isolated arteries in the absence or in the presence of BQ-123/788.. Total and high-molecular-weight Ad was significantly decreased and ET-1 levels significantly increased in OW (P < .01) and Ob (P < .001) children. A statistically significant linear regression (P < .01) was found between Ad and ET-1. Exposure of adipocytes to exogenous ET-1 or serum from OW and Ob significantly decreased Ad mRNA and protein levels (P < 0.001). The inhibitory effect of ET-1 on Ad was reverted by BQ-123/788 or PD-98059 but not SP-600125. Ad-mediated vasodilation was further increased in arteries pretreated with BQ-123/788.. ET-1-mediated inhibition of Ad synthesis via p42/44 MAPK signaling may provide a possible explanation for hypoadiponectinemia in pediatric obesity and contribute to the development of cardiovascular complications.

Topics: 3T3-L1 Cells; Adiponectin; Age of Onset; Animals; Child; Endothelin-1; Female; Humans; Male; MAP Kinase Signaling System; Metabolism, Inborn Errors; Mice; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Obesity; Overweight; Rats; Rats, Wistar; Thinness

To investigate the effect of a short-term yoga-based lifestyle intervention on risk factors for cardiovascular disease (CVD) and markers of inflammation and endothelial function in overweight and obese men.. Nonrandomized prospective lifestyle intervention study with pre-post design. SETTING AND LOCATION: Integral Health Clinic, an outpatient facility providing yoga-based lifestyle intervention programs for prevention and management of chronic diseases.. Overweight and obese men (n=51) were enrolled in the study. Subjects who were physically unable to participate and those participating in other interventions were excluded from the study.. A pretested intervention program including asanas (physical postures), pranayama (breathing exercises), group discussions, lectures, and individualized advice.. The primary outcome measure was weight loss, and the secondary outcome measures were clinical and laboratory correlates of CVD risk, levels of interleukin-6 (IL-6), adiponectin, and endothelin-1 (ET-1).. Men (n=51, body mass index [BMI] 26.26±2.42 kg/m(2)) were enrolled and underwent a yoga-based lifestyle intervention for 10 days. Of 51 subjects, 30 completed the study. There was a significant reduction in weight from Baseline to Day 10 (74.60±7.98, 72.69±8.37 kg, p<0.001, respectively), BMI (26.26±2.42, 25.69±2.47 kg/m(2), p<0.001, respectively), and systolic BP (121.73±11.58, 116.73±9.00, p=0.042, respectively). There was a significant reduction in plasma IL-6 from Baseline to Day 10 (median 2.24 vs. 1.26 pg/mL, respectively, p=0.012). There was a significant increase in the plasma adiponectin from Baseline to Day 10 (median 4.95 vs. 6.26 μg/mL, respectively, p=0.014). Plasma ET-1 level remained unchanged.. These findings suggest that even a short-term yoga-based lifestyle intervention may be an important modality to reduce the risk for CVD as indicated by weight loss, reduction in systolic blood pressure, an increase in adiponectin, and decrease in IL-6 in overweight and obese men.

Topics: Adiponectin; Adolescent; Adult; Blood Pressure; Body Mass Index; Body Weight; Cardiovascular Diseases; Endothelin-1; Humans; Interleukin-6; Life Style; Lipoproteins; Male; Middle Aged; Obesity; Overweight; Prospective Studies; Pulse; Risk Factors; Yoga; Young Adult

Endothelin (ET)-1-mediated vasoconstrictor tone contributes to the development and progression of several adiposity-related conditions, including hypertension and atherosclerotic vascular disease. The aims of the present study were to determine 1) whether endogenous ET-1 vasoconstrictor activity is elevated in overweight and obese adults, and, if so, 2) whether increased ET-1-mediated vasoconstriction contributes to the adiposity-related impairment in endothelium-dependent vasodilation. Seventy-nine adults were studied: 34 normal weight [body mass index (BMI) < 25 kg/m(2)], 22 overweight (BMI ≥ 25 and < 30 kg/m(2)), and 23 obese (BMI ≥ 30 kg/m(2)). Forearm blood flow (FBF) responses to intra-arterial infusion of ET-1 (5 pmol/min for 20 min) and selective ET-1 receptor blockade (BQ-123, 100 nmol/min for 60 min) were determined. In a subset of the study population, FBF responses to ACh (4.0, 8.0, and 16.0 μg·100 ml tissue(-1)·min(-1)) were measured in the absence and presence of selective ET-1 receptor blockade. The vasoconstrictor response to ET-1 was significantly blunted in overweight and obese adults (∼ 70%) compared with normal weight adults. Selective ET-1 receptor blockade elicited a significant vasodilator response (∼ 20%) in overweight and obese adults but did not alter FBF in normal weight adults. Coinfusion of BQ-123 did not affect FBF responses to ACh in normal weight adults but resulted in an ∼ 20% increase (P < 0.05) in ACh-induced vasodilation in overweight and obese adults. These results demonstrate that overweight and obesity are associated with enhanced ET-1-mediated vasoconstriction that contributes to endothelial vasodilator dysfunction and may play a role in the increased prevalence of hypertension with increased adiposity.

Topics: Adiposity; Adult; Aged; Analysis of Variance; Blood Pressure; Body Mass Index; Case-Control Studies; Dose-Response Relationship, Drug; Endothelin A Receptor Antagonists; Endothelin-1; Endothelium, Vascular; Female; Forearm; Humans; Infusions, Intravenous; Male; Middle Aged; Obesity; Overweight; Peptides, Cyclic; Receptor, Endothelin A; Regional Blood Flow; Regression Analysis; Time Factors; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents

The effect of habitual exercise on vascular function, including central arterial distensibility and endothelial function, in obese subjects has not yet been clarified. We investigated whether aerobic exercise training affects central arterial distensibility and endothelial function in middle-age overweight and obese men. A total of 21 overweight and obese men (age 50 +/- 2 years, body mass index 30 +/- 1 kg/m(2)) completed a 12-week aerobic exercise intervention. Aerobic exercise training significantly reduced their body weight and resulted in a significant decrease in body mass index. After the weight-reduction exercise program, carotid arterial compliance (determined by simultaneous B-mode ultrasonography and arterial applanation tonometry on the common carotid artery) significantly increased; and the beta-stiffness index, an index of arterial compliance adjusted for distending pressure, significantly decreased. The concentrations of plasma endothelin-1, a potent vasoconstrictor peptide produced by vascular endothelial cells, significantly decreased and plasma nitric oxide (measured as the stable end product [nitrite/nitrate]), a potent vasodilator produced by vascular endothelial cells, significantly increased after the weight-reduction exercise program. In conclusion, weight reduction by aerobic exercise training in overweight and obese men increased the central arterial distensibility. This increase might contribute to the improvement in endothelial function, as assessed by a decrease in endothelin-1 and an increase in nitric oxide, after exercise training-induced weight loss.

Topics: Absorptiometry, Photon; Adult; Body Weight; Endothelin-1; Endothelium, Vascular; Exercise; Humans; Male; Manometry; Middle Aged; Nitric Oxide; Obesity; Overweight; Oxygen Consumption

To verify if patients with polycystic ovarian syndrome (PCOS), have an increased cardiovascular risk compared with healthy controls.. Prospective case-control study.. University-based practice.. Twenty eumenorrheic controls (ten lean [group A] and ten overweight [group B]) and 24 PCOS women (14 lean [group C] and ten overweight [group D]).. Cardiovascular risk markers and hormonal parameters were assessed.. Androgens, fasting glucose, insulin, leptin, fibrinogen, homocysteine, endothelin-1 and flow-mediated dilatation of the brachial artery were measured to investigate their relationship to weight and to PCOS.. The brachial artery diameter and the pulsatility index, after the reactive hyperemia, showed in group A the most intense vasodilatation compared with the other groups. Homocysteine levels did not differ among the groups. Endothelin-1 was significantly higher in group A compared with groups B and D. Leptin was significantly lower in groups A and C compared with groups B and D. Insulin resistance was higher in groups B and D. Group A had significantly higher glucose-insulin ratio compared with all of the other groups; group C had significantly higher glucose-insulin ratio only compared with group D.. Weight and PCOS are two independent variables affecting the endothelial function.

Topics: Adult; Androgens; Blood Flow Velocity; Brachial Artery; Case-Control Studies; Endothelin-1; Endothelium, Vascular; Female; Fibrinogen; Homocysteine; Humans; Insulin; Insulin Resistance; Leptin; Menstruation; Overweight; Polycystic Ovary Syndrome; Progesterone; Vasodilation; Young Adult

Endothelin-1 (ET-1) has been found to be higher in hypertensive African Americans and obese hypertensive Caucasians compared to normotensive controls with an enhanced ET-1-dependent vasoconstrictor tone. ET-1 levels and the associations thereof with cardiovascular function in overweight/obese normotensive and hypertensive African women have not been investigated. It is therefore hypothesized that ET-1 levels are elevated in overweight/obese hypertensive African women compared to overweight/obese and lean normotensive controls. Additionally, it is hypothesized that these elevated ET-1 levels are associated with increased total peripheral resistance (TPR) and decreased arterial compliance (C(W)).. A case-case control study was performed which included 98 African women. The subjects were divided into lean normotensive (lean NT), overweight/obese normotensive (OW/OB NT) and overweight/obese hypertensive (OW/OB HT). The Finometer apparatus was used to obtain a more elaborate cardiovascular profile and plasma immunoreactive ET-1 levels were determined.. ET-1 levels were similar for the three groups. Although a decrease in vascular function was observed in the OW/OB HT group, no correlations were obtained between ET-1 and the cardiovascular profile, before and after adjusting for age.. In African women, ET-1 levels did not differ between lean and overweight/obese and normotensive and hypertensive subjects. The lack of significant associations between ET-1 and decreased vascular function in the overweight/obese hypertensive group suggests that ET-1 is not implicated in obesity-related hypertension in African women.

Topics: Adult; Africa; Blood Pressure; Case-Control Studies; Endothelin-1; Female; Humans; Hypertension; Middle Aged; Obesity; Overweight; Vascular Resistance