Influence of Metabolic Syndrome on Biomarkers of Oxidative Stress and Inflammation in Obese Adults

Guilder, Gary P. Van; Hoetzer, Greta L.; Greiner, Jared J.; Stauffer, Brian L.; DeSouza, Christopher A.

doi:10.1038/oby.2006.248

Cited by 195 publications

(150 citation statements)

References 18 publications

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“…Plasma concentrations of C-reactive protein (CRP) and oxidized low-density lipoprotein (ox-LDL) were determined by high-sensitivity enzyme immunoassay (ALPCO Diagnostics, R&D Systems). 23 Intra-assay and interassay coefficients of variation were 7.8% and 3.0%, respectively, for CRP and 5.3% and 3.3%, respectively, for oxLDL.…”

Section: Metabolic Measurementsmentioning

confidence: 86%

Endothelin-1 Vasoconstrictor Tone Increases With Age in Healthy Men But Can Be Reduced by Regular Aerobic Exercise

Guilder

Westby²,

Greiner³

et al. 2007

Hypertension

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144

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Abstract-Increased endothelin-1-mediated vasoconstrictor tone has been linked to the etiology of a number of pathologies associated with human aging, including hypertension, congestive heart failure, and coronary artery disease. However, it is currently unclear whether aging, per se, is associated with enhanced endothelin-1 system activity. We hypothesized that endothelin-1 vasoconstrictor activity is greater in healthy older compared with young men and that regular aerobic exercise is an effective intervention for reducing endothelin-1 vasoconstrictor tone in older previously sedentary men. Forearm blood flow (plethysmography) responses to intra-arterial infusion of endothelin-1 (5 pmol/min; for 20 minutes) and selective (BQ-123; 100 nmol/min; for 60 minutes) and nonselective (BQ-123ϩBQ-788; 100 nmol/min; for 60 minutes) endothelin-1 receptor blockade were determined in 28 healthy, sedentary men: 13 younger (age: 27Ϯ1 years) and 15 older (age: 62Ϯ2 years). The vasoconstrictor response to endothelin-1 was significantly blunted (Ϸ65%) in the older versus younger men. In response to BQ-123, resting forearm blood flow increased (Ϸ20%; PϽ0.05) in the older but not in the younger men. Key Words: elderly Ⅲ exercise Ⅲ endothelin Ⅲ blood flow regulation M any of the cardiovascular complications associated with aging (eg, hypertension, arterial spasm, and myocardial infarction) are attributable, at least in part, to endothelial dysfunction, particularly vasomotor dysregulation. 1-3 Impaired vasomotor function occurs early in the atherosclerotic process, contributes to disease development and progression, and can trigger acute cardiovascular events. 4 -6 In addition to the synthesis and release of relaxing factors, such as NO, the vascular endothelium also produces contracting factors, the most potent of which is endothelin (ET)-1. Produced by the proteolytic cleavage of big ET-1 by ET converting enzyme, endothelial ET-1 is predominantly (Ͼ80%) released abluminally toward the vascular smooth muscle. 7 Binding of ET-1 to ET A and ET B receptors on vascular smooth muscle cells activates the phospholipase C-inositol triphosphate pathway resulting in an increase in intracellular calcium causing phosphorylation of myosin kinase and, in turn, long-lasting smooth muscle cell contraction. 7,8 Importantly, increased ET-1-mediated vasoconstriction has been linked to the etiology of a number of cardiovascular pathologies, including hypertension, vasospasm, coronary artery disease, and chronic heart failure. 8 -10 There is strong evidence in animal models that aging is associated with elevated ET-1 system activation. 11,12 However, data regarding the influence of aging on ET-1 system activity in adult humans are limited. Kumazaki et al 13 reported that cultured endothelial cells from the aorta of adults over the age of 50 years produce and release more ET-1 compared with cells from younger adults. Some studies have reported age-related increases in circulating levels of ET-1 14,15 ; however, the pathophysiological significance of ...

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Section: Metabolic Measurementsmentioning

confidence: 86%

Endothelin-1 Vasoconstrictor Tone Increases With Age in Healthy Men But Can Be Reduced by Regular Aerobic Exercise

Guilder

Westby²,

Greiner³

et al. 2007

Hypertension

Self Cite

144

View full text Add to dashboard Cite

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“…2 Indeed, recent studies showed a positive relationship between obesity, inflammatory C-reactive protein, 3 and oxidized low-density lipoprotein (ox-LDL). 4,5 Moreover, we showed that ox-LDL was associated with the incidence of the metabolic syndrome 6 and with several metabolic syndrome components, especially visceral obesity. 7,8 Stevioside was found to exert antihyperglycemic and insulinotropic effects in a non-obese animal model of type 2 diabetes 9 by acting directly on pancreatic cells.…”

Section: Introductionmentioning

confidence: 94%

Stevioside inhibits atherosclerosis by improving insulin signaling and antioxidant defense in obese insulin-resistant mice

et al. 2009

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Objective: Stevioside is a non-caloric natural sweetener that does not induce a glycemic response, making it attractive as sweetener to diabetics and others on carbohydrate-controlled diets. Obesity is frequently associated with insulin resistance and increased inflammation and oxidative stress. Therefore, we investigated its effects on insulin resistance, inflammation and oxidative stress related to atherosclerosis in obese insulin-resistant mice.Research design: Twelve-week-old mice were treated with stevioside (10 mg kg À1 , n ¼ 14) or placebo (n ¼ 20) for 12 weeks. Results: Stevioside had no effect on weight and triglycerides, but lowered glucose and insulin. Stevioside treatment improved adipose tissue maturation, and increased glucose transport, insulin signaling and antioxidant defense in white visceral adipose tissues. Together, these increases were associated with a twofold increase of adiponectin. In addition, stevioside reduced plaque volume in the aortic arch by decreasing the macrophage, lipid and oxidized low-density lipoprotein (ox-LDL) content of the plaque. The higher smooth muscle cell-to-macrophage ratio was indicative for a more stable plaque phenotype. The decrease in ox-LDL in the plaque was likely due to an increase in the antioxidant defense in the vascular wall, as evidenced by increased Sod1, Sod2 and Sod3. Circulating adiponectin was associated with improved insulin signaling and antioxidant defense in both the adipose tissue and the aorta of stevioside-treated mice. Conclusion: Stevioside treatment was associated with improved insulin signaling and antioxidant defense in both the adipose tissue and the vascular wall, leading to inhibition of atherosclerotic plaque development and inducing plaque stabilization.

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“…10,15,16 MetS should be associated with an increase in oxidative stress, [17][18][19] possibly through enhanced ROS-inducible adipocytokines. 20 -22 Also, salt loading increased oxidative stress in several salt-sensitive hypertension models.…”

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confidence: 99%

Salt Excess Causes Left Ventricular Diastolic Dysfunction in Rats With Metabolic Disorder

et al. 2008

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Abstract-Metabolic syndrome is a highly predisposing condition for cardiovascular disease and could be a cause of excess salt-induced organ damage. Recently, several investigators have demonstrated that salt loading causes left ventricular diastolic dysfunction associated with increased oxidative stress and mineralocorticoid receptor activation. We, therefore, investigated whether excess salt induces cardiac diastolic dysfunction in metabolic syndrome via increased oxidative stress and upregulation of mineralocorticoid receptor signals. Thirteen-week-old spontaneously hypertensive rats and SHR/NDmcr-cps, the genetic model of metabolic syndrome, were fed a normal salt (0.5% NaCl) or high-salt (8% NaCl) diet for 4 weeks. In SHR/NDmcr-cps, salt loading induced severe hypertension, abnormal left ventricular relaxation, and perivascular fibrosis. Salt-loaded SHR/NDmcr-cps also exhibited overproduction of reactive oxygen species and upregulation of mineralocorticoid receptor-dependent gene expression, such as Na ϩ /H ϩ exchanger-1 and serumand glucocorticoid-inducible kinase-1 in the cardiac tissue. However, in spontaneously hypertensive rats, salt loading did not cause these cardiac abnormalities despite a similar increase in blood pressure. An antioxidant, tempol, prevented salt-induced diastolic dysfunction, perivascular fibrosis, and upregulation of mineralocorticoid receptor signals in SHR/NDmcr-cps. Moreover, a selective mineralocorticoid receptor antagonist, eplerenone, prevented not only diastolic dysfunction but also overproduction of reactive oxygen species in salt-loaded SHR/NDmcr-cps. These results suggest that metabolic syndrome is a predisposed condition for salt-induced left ventricular diastolic dysfunction, possibly via increased oxidative stress and enhanced mineralocorticoid receptor signals. which eventually leads to diastolic heart failure with a poor prognosis. 5,6 However, LV diastolic dysfunction has not always been seen in a MetS animal model. For example, in obesity-prone Sprague-Dawley rats, a moderate fat diet induced metabolic abnormalities but did not cause LV diastolic dysfunction. 7 This discrepancy indicates a possibility that some exogenous factors deteriorate cardiac function in MetS. In patients with MetS, high salt intake increased blood pressure (BP) greater than in those without MetS. 8 In an MetS rat model, evident renal injury was induced by salt loading. 9 These findings suggest that the MetS model is highly susceptible to salt-induced organ damage. Salt loading induced LV hypertrophy or LV diastolic dysfunction in several hypertension models. 10 -14 Therefore, it is speculated that LV diastolic impairment could be accelerated with excess salt in an MetS model.Reactive oxygen species (ROS) are important elements causing cardiac functional damage. 10,15,16 MetS should be associated with an increase in oxidative stress, 17-19 possibly through enhanced ROS-inducible adipocytokines. 20 -22 Also, salt loading increased oxidative stress in several salt-sensitive hypertension models...

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Influence of Metabolic Syndrome on Biomarkers of Oxidative Stress and Inflammation in Obese Adults

Cited by 195 publications

References 18 publications

Endothelin-1 Vasoconstrictor Tone Increases With Age in Healthy Men But Can Be Reduced by Regular Aerobic Exercise

Endothelin-1 Vasoconstrictor Tone Increases With Age in Healthy Men But Can Be Reduced by Regular Aerobic Exercise

Stevioside inhibits atherosclerosis by improving insulin signaling and antioxidant defense in obese insulin-resistant mice

Salt Excess Causes Left Ventricular Diastolic Dysfunction in Rats With Metabolic Disorder

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