8-epi-prostaglandin-f2alpha and Obesity

Epidemiological data has established increasing adiposity as a risk factor for incident asthma. However, the mechanisms underlying the association between obesity and asthma are incompletely understood. In the present paper, we review current knowledge of possible mechanisms mediating the observed association between obesity and asthma.. Systematic literature review.. Obesity and asthma share some etiological factors, such as a common genetic predisposition and effects of in utero conditions, and may also have common predisposing factors such as physical activity and diet. Obesity results in important changes in the mechanical properties of the respiratory system which could explain the occurrence of asthma. However, there are also plausible biological mechanisms whereby obesity could be expected to either cause or worsen asthma. These include co-morbidities such as gastro-oesophageal reflux, complications from sleep-disordered breathing, breathing at low lung volumes, chronic systemic inflammation, and endocrine factors, including adipokines and reproductive hormones. Obesity related asthma is in general not associated with eosinophilic airway inflammation, and adipokines are likely to play important roles in the inflammatory pathogenesis of asthma in obese individuals.. The association between obesity and asthma is not straightforward, and further knowledge is clearly needed, as understanding the underlying mechanisms may lead to new therapeutic options for this high-risk part of the asthma population.

Topics: Adipokines; Adiposity; Adolescent; Adult; Aged; Asthma; Biomarkers; Body Mass Index; Dinoprost; Environment; Epigenesis, Genetic; Female; Genetic Predisposition to Disease; Humans; Life Style; Lung; Male; Middle Aged; Obesity; Oxidative Stress; Respiratory Function Tests; Sex Factors; Young Adult

Overweight is associated with alterations in lipid concentrations and an activation of inflammatory markers and both of these metabolic abnormalities are characteristic of preeclamptic pregnancies before the onset of clinically evident disease. Reactive oxygen species, particularly superoxide anions, evoke endothelial cell activation through many pathways. Markers of lipid peroxidation, including malondialdehyde and 8-epiprostaglandin-F2α, is increased in the plasma of women with preeclampsia, and the low concentrations of water- and lipid-soluble antioxidants in the plasma and the placenta further suggest a state of oxidative stress. This review focuses in the relation between maternal obesity, oxidative stress with development of preeclampsia.

Topics: Antioxidants; Dinoprost; Female; Humans; Inflammation; Lipid Peroxidation; Malondialdehyde; Obesity; Oxidative Stress; Placenta; Placentation; Pre-Eclampsia; Pregnancy; Reactive Oxygen Species

Obesity is associated with increased systemic and airway oxidative stress, which may result from a combination of adipokine imbalance, comorbidities, and reduced antioxidant defenses. While obesity-mediated increased oxidative stress plays an important role in the pathogenesis of vascular disease and nonalcoholic hepatic steatosis, little is known of how it may affect the lung. Contrary to what has previously been thought, the combination of obesity and asthma, both chronic inflammatory diseases, does not necessarily result in a synergistic effect, leading to even greater oxidative stress. However, most available studies have compared the levels of oxidative stress biomarkers on stable asthma patients, and it is possible that the interaction of oxidative stress between obesity and asthma is not readily detectable under basal conditions. We propose that obesity-mediated oxidative stress, which may affect the lung function of asthmatic subjects by increasing airway inflammation and reducing the effectiveness of inhaled corticosteroids, may become evident during exposure to an aggravating factor or during periods of asthma exacerbation. Understanding whether obesity-mediated oxidative stress has a mechanistic role in the association between obesity and asthma will help in the formation of public health policies and increase our capacity to develop therapeutic interventions that improve the life of obese asthmatic subjects.

Topics: Adipokines; Animals; Asthma; Dinoprost; Humans; Inflammation Mediators; Lung; Obesity; Oxidative Stress; Risk Factors

Obesity is becoming one of the leading risk factors of coronary heart disease, hypertension, cerebrovascular disease. Despite the presence of a large number of antihypertensive agents and scientific substantiation of antihypertensive treatment principles it would be wrong to assume that the problem is completely solved. Development of endothelial dysfunction is one of the key pathogenic mechanisms in hypertension. This process is proven to have contributed by immune inflammation activation which is mediated by pro-inflammatory cytokines and oxidative stress.. To investigate the additional benefits of the combined antihypertensive therapy with lacidipine and candesartan on the basis of studying their antioxidant properties, impact on endothelial function and pro-inflammatory cytokines activity in hypertensive patients with overweight and obesity.. A combination of a calcium channel blocker and angiotensin receptor blocker (lacidipine 2 mg, 4 mg, and candesartan 4mg, 8mg, 16mg) was prescribed to 30 patients with essential hypertension of grades 1-3, 30 to 65 years old (mean age - 54.7 ± 5.8 years), who previously have not been receiving regular antihypertensive therapy.. During the course of combined antihypertensive therapy with lacidipine and candesartan, a significant reduction in i-NOS activity, TNF-α to its type I soluble receptor ratio (TNF- α/sTNF-αRI), and oxidative stress marker - 8-iso-PgF2α has been observed. Activity of e-NOS, levels of SOD and catalase, in contrast, have increased by the end of observation period.. The improvement of endothelial function due to lower level of oxidative stress and a significant decrease of immune activation has been observed in hypertensive patients with overweight and obesity under the influence of combined antihypertensive therapy with lacidipine and candesartan.

Topics: Adult; Aged; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Case-Control Studies; Dihydropyridines; Dinoprost; Drug Therapy, Combination; Endothelium, Vascular; Female; Humans; Hypertension; Male; Middle Aged; Obesity; Tetrazoles; Tumor Necrosis Factor-alpha

The impact of excess weight on cardiovascular disease risk in type 1 diabetes patients is unclear.. This study examined associations of BMI and body composition with cardiovascular risk factors in youth followed prospectively for 18 months.. The sample includes youth with type 1 diabetes (N = 136, baseline age = 12.3 ± 2.5y, glycated hemoglobin = 8.1 ± 1.1%) participating in an 18-month behavioral nutrition intervention trial. BMI, body composition (by dual energy x-ray absorptiometry), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C); triglycerides (TG), c-reactive protein (CRP), 8-iso-prostaglandin-F2alpha (8-iso-PGF2α), adiponectin and systolic and diastolic blood pressure (SBP and DBP, respectively) were assessed at clinic visits every 6 months. Random effects regression models for repeated measures estimated associations of time-varying BMI and body composition with time-varying cardiovascular risk factors, adjusted for treatment assignment and covariates.. There was no intervention effect on cardiovascular risk factors. Percent body fat was positively associated with TG, LDL-C, CRP, SBP and DBP, while trunk fat mass and trunk %fat were associated positively with TG, LDL-C, CRP, SBP and DBP, and inversely with HDL-C. Higher BMI was associated with greater TG, CRP, SBP and DBP and lower HDL-C. BMI and body composition indicators were unrelated to 8-iso-PGF2α and adiponectin.. Excess adiposity is associated with increased cardiovascular risk factors in this sample of youth with type 1 diabetes. Non-significant associations with adiponectin and 8-iso-PGF2α suggest potential differences from the general population in the role of adiposity in cardiovascular health.

Topics: Absorptiometry, Photon; Adiposity; Adolescent; Biomarkers; Blood Pressure; Body Composition; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Child; Diabetes Mellitus, Type 1; Dinoprost; Female; Glycated Hemoglobin; Humans; Lipids; Male; Obesity; Prospective Studies; Risk Factors

The optimal amount of vegetable consumption required to reduce chronic disease risk is widely debated. Intervention trials evaluating biological activity of vegetables at various doses are limited. We conducted a 3-dose, crossover feeding trial to test the hypothesis that vegetable intake is associated in a dose-dependent manner with increased plasma carotenoids and subsequently reduced oxidative stress and inflammation in 49 overweight, postmenopausal women. Participants were assigned in random order to 2 (130 g), 5 (287 g), and 10 (614 g) daily servings of fresh, greenhouse-grown vegetables for 3-wk intervals with a 4-wk washout period between treatments. Plasma total carotenoids significantly increased from 1.63 to 2.07 μmol/L with a dose of 2 vegetable servings, from 1.49 to 2.84 μmol/L with a dose of 5 vegetable servings, and from 1.40 to 4.42 μmol/L with a dose of 10 vegetable servings (pre-post paired ttests, all P < 0.001). The change during each feeding period increased with each dose level (P < 0.001). Urine concentrations of 8-isoprostane F2α, hexanoyl lysine, and serum high sensitivity C-reactive protein were not affected by any administered vegetable dose. In this variable-dose vegetable study, a dose-response for plasma carotenoids was demonstrated without significant change in oxidative stress and inflammation in overweight, postmenopausal women.

Topics: Aged; Arizona; Biomarkers; Body Mass Index; C-Reactive Protein; Carotenoids; Chronic Disease; Cross-Over Studies; Dinoprost; Female; Humans; Lysine; Middle Aged; Obesity; Overweight; Oxidative Stress; Postmenopause; Risk Factors; Vegetables

Oxidative stress can initiate increased inflammation that elevates risk for cardiovascular disease. The objective of this study was to determine the effects of daily consumption of raisins on markers of oxidative stress, inflammation and endothelial activation in response to an acute high-fat meal in overweight individuals.. Seventeen overweight men and women consumed 90 g raisins or isocaloric placebo (264 kcal/day) for 14 days in a randomized, crossover design while following a low-flavonoid diet. The oxidative [urinary 8-iso-prostaglandin-F(2alpha) (8-epi PGF(2alpha)) and serum oxygen radical absorbance capacity (ORAC)], inflammatory (serum C-reactive protein and interleukin-6), endothelial (serum soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1, sVCAM-1) and metabolic [free fatty acids (FFAs), triacylglycerol, glucose and insulin] response to four high-fat (53%) meals was tested pre- and postintervention.. Urinary 8-epi PGF(2alpha) decreased (-22%) and fasting ORAC increased (+3%) after both interventions combined. Fasting protein-free ORAC was modestly (+3.5%) higher during the raisin than the placebo intervention. Neither the meals nor the raisins consistently induced fasted markers of inflammation or endothelial dysfunction. Gender influenced postprandial metabolic responses in that males responded with higher serum FFAs, sVCAM-1 and glucose compared with females.. Serum antioxidant capacity was modestly increased by daily raisin consumption, but this did not alter fasted or postprandial inflammatory response in these relatively healthy but overweight individuals. Providing all food in regular pattern reduced measures of oxidative stress.

Topics: Adult; Analysis of Variance; Biomarkers; Blood Glucose; C-Reactive Protein; Cross-Over Studies; Diet, Reducing; Dinoprost; Fatty Acids, Nonesterified; Feeding Behavior; Female; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-6; Male; Obesity; Oxidative Stress; Phytotherapy; Postprandial Period; Sex Factors; Vascular Cell Adhesion Molecule-1; Vitis; Young Adult

The objective of this study was to test the hypothesis that the inflammatory response to a high-fat, low-carbohydrate weight loss diet (HF) we previously observed was due to oxidative stress. Nineteen overweight subjects (BMI>27 kg/m(2)) were randomly assigned to either an antioxidant supplement (AS) (1 g vitamin C/800 IU vitamin E) or a placebo (P) group and provided with a HF for 7 days. Fasted pre- and post serum samples were measured for markers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1)), oxygen radical absorbance capacity (ORAC), and glucose, whereas urine was measured for oxidative stress (8-epi-prostaglandin-F(2alpha) (8-epi)). HF resulted in significant reductions in weight (-3.2%), glucose (-18.7%), and MCP-1 (-15%) (all P<0.01), with no difference between groups. There was a trend for a differential effect between groups for CRP as it decreased 32% in the AS group but increased 50% for P (P=0.076). Inverse correlations were noted between initial values and changes in several inflammatory and oxidative stress markers, including CRP (r= -0.501), 8-epi (r= -0.863), and ORAC (r= -0.546) (all P<0.05). It was concluded that weight loss on a short-term HF caused reduction of some but not all markers of inflammation. A role for oxidative stress in causing inflammation was not confirmed; however, longer term diet-controlled studies are necessary to further explore the trend for a differential response in CRP with antioxidant supplementation.

Topics: Antioxidants; Ascorbic Acid; Biomarkers; Blood Glucose; C-Reactive Protein; Chemokine CCL2; Diet, Carbohydrate-Restricted; Dietary Fats; Dinoprost; Drug Combinations; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Male; Obesity; Oxidative Stress; Reactive Oxygen Species; Time Factors; Treatment Outcome; Vitamin E; Weight Loss

In the present study, the authors examined the relationship between lipid peroxidation and inflammation in patients with obstructive sleep apnoea (OSA). A total of 40 obese patients with OSA were studied, along with 18 obese and 12 lean subjects without OSA. Overnight excretion of 8-isoprostane in urine and serum levels of high-sensitivity C-reactive protein (hsCRP) were measured. In addition, the effects of 3 months' treatment with nasal continuous positive airway pressure (nCPAP) were studied in 20 obese patients with moderate-to-severe OSA. Overnight urinary excretion of 8-isoprostane and serum levels of hsCRP were significantly higher in patients with moderate-to-severe OSA compared with patients with mild OSA and obese or lean subjects without OSA. Overnight urinary excretion of 8-isoprostane significantly correlated with apnoea-hypopnoea index, duration of hypoxia during sleep, body mass index, and serum levels of hsCRP in patients with OSA. The severity of OSA was an independent factor predicting the urinary excretion of 8-isoprostane. nCPAP significantly decreased urinary excretion of 8-isoprostane and serum levels of hsCRP. In conclusion, these results suggest that both obstructive sleep apnoea severity and obesity can independently contribute to elevations in urinary excretion of 8-isoprostane. Therefore, obstructive sleep apnoea may increase the risks of cardiovascular morbidity in obese patients.

Topics: C-Reactive Protein; Cardiovascular Diseases; Dinoprost; Humans; Inflammation; Lipid Peroxidation; Male; Middle Aged; Obesity; Sleep Apnea, Obstructive

Obesity is associated with increased levels of inflammatory mediators. The objective of this study was to evaluate changes in the leucocyte derived inflammatory mediators tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and the isoprostane 8-epi-prostaglandin (PG) F2alpha during BMI lowering with orlistat (Xenical(R), Roche) or placebo.. TNF-alpha, IL-6, and 8-epi PGF2alpha evaluated in 376 subjects aged 18-75 years with BMI 28-38 kg/m2 before and after 1 year of double-blind, randomized treatment with orlistat 120 mg or placebo three times daily.. Weight reduction was associated with decreasing (p < 0.001) levels of TNF-alpha and IL-6 in both orlistat and placebo groups. After 12 months, TNF-alpha was lower (p < 0.05) in the orlistat compared with the placebo group. In the orlistat group, the change in TNF-alpha correlated with change in s-glucose (r = 0.22; p = 0.01), and the change in 8-epi-PGF2alpha correlated with changes in s-cholesterol (r = 0.27; p < 0.001) and s-LDL-cholesterol (r = 0.28; p < 0.001).. Weight reduction was associated with decreasing levels of both TNF-alpha and IL-6. After 12 months of treatment, TNF-alpha levels were lower in orlistat than in placebo-treated subjects. Whether these results translate into reduced incidence of cardiovascular disease remains to be elucidated.

Topics: Adolescent; Adult; Aged; Anti-Obesity Agents; Body Mass Index; Cardiovascular Diseases; Dinoprost; Double-Blind Method; Female; Follow-Up Studies; Humans; Interleukin-6; Lactones; Lipids; Male; Middle Aged; Obesity; Orlistat; Risk Factors; Tumor Necrosis Factor-alpha; Weight Loss

Advancing age is a major risk factor for a range of diseases such as, cardiovascular disease, diabetes, cancer and neurodegenerative diseases. In addition, over a third of the population are overweight and obesity is becoming more prevalent in younger people. Ageing and obesity are both linked to a chronic proinflammatory state and elevated oxidative stress, which have both been implicated in cardiovascular and neurodegenerative diseases. Platelets contain all the necessary machinery to process the Amyloid precursor protein AβPP, a pathway thought to be perturbed in Alzheimer's Disease (AD). The ratio of AβPP isoforms present in platelets, and the amount of alpha secretase ADAM10, that works to process AβPP, appear to be associated with cognitive decline and a diagnosis of Alzheimer's disease. The aim of this study was to assess changes in AβPP ratio, ADAM10 and markers of inflammation and oxidative stress with ageing and obesity.. Ninety participants were recruited to this study to provide one blood sample. Platelet-rich plasma and platelet lysates were collected and the expression of AβPPr, proADAM10 and mADAM10 was assessed by Western blotting. In addition, markers of inflammation (IL-6) and oxidative stress (8-Isoprostane) were assessed in plasma.. Participants were placed into one of four groups based on their age and body mass index (Young/Lean, Young/obese, Old/Lean and Old/Obese). IL-6 was able to significantly distinguish obese from lean participants (AUC of 0.80, SE = 0.05, P < 0.001). Plasma isoprostanes were able to distinguish between both young/old (AUC of 0.73, SE = 0.05, P < 0.01), and obese/non-obese participants (AUC of 0.66, SE = 0.01, P < 0.01). Plasma protein carbonyls could distinguish young and old participants (AUC of 0.69, SE = 0.07 P < 0.02). Old Lean participants had significantly lower mADAM10 expression than both Young Lean and Young Obese participants (p < 0.05). Old obese participants had significantly lower proADAM10 expression compared to both Young Lean and Young Obese (p < 0.05). Both mADAM10 and proADAM10 were significantly decreased with advancing age (p < 0.05).. The findings presented in this study provide evidence that blood-based biomarkers related to the pathology of AD are altered with age and obesity in otherwise healthy adults. Ageing was more strongly associated with elevated markers of oxidative stress whereas obesity was associated with elevated inflammatory IL-6.

Topics: ADAM10 Protein; Adult; Aged; Aging; Alzheimer Disease; Amyloid beta-Protein Precursor; Amyloid Precursor Protein Secretases; Biomarkers; Blood Platelets; Body Mass Index; Dinoprost; Female; Humans; Inflammation; Male; Obesity; Oxidative Stress; Plasma; Young Adult

To evaluate the plasma level of 8-isoprostanes in women with polycystic ovary syndrome. To also investigate whether there is a relationship between 8-isoprostanes and several cardiovascular risk factors.. A total of 125 women with polycystic ovary syndrome and 169 healthy women were enrolled in this case-control study. 8-Isoprostanes and different parameters were measured in all subjects. Patients were evaluated for the presence of polycystic ovary syndrome according to the Rotterdam Consensus Conference criteria.. 8-Isoprostanes levels were significantly higher in patients with polycystic ovary syndrome (138.4 ± 104.1 pg/mL) compared with control group (68.6 ± 34.3 pg/mL) (p < 0.001). The mean of triglycerides, lipid accumulation product, C-reactive protein, homocysteine, insulin, and homeostatic model assessment for insulin resistance were significantly higher in polycystic ovary syndrome patients with high 8-isoprostanes than those with normal 8-isoprostanes (p < 0.05). The Pearson correlation analyses showed that 8-isoprostanes levels in polycystic ovary syndrome group had a positive correlation with waist circumference, triglycerides, low-density lipoprotein cholesterol, apolipoprotein B, homocysteine, insulin, homeostatic model assessment for insulin resistance.. Patients with polycystic ovary syndrome have higher 8-isoprostanes levels and it is associated with several cardiovascular risk factors.

Topics: Adult; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Dinoprost; Female; Humans; Isoprostanes; Obesity; Polycystic Ovary Syndrome; Risk Factors; Young Adult

This study aims to investigate the correlation between oxidative stress and intra-abdominal fat (IAF) in obese young and middle-aged males.The present study included 136 male examinees in the Examination Center of the First Hospital of Qinhuangdao from October 10, 2015 to December 10, 2015. Then, clinical data, oxidative stress indices (8-iso-prostaglandin F2α [8-iso-PGF2α], malondialdehyde [MDA], and superoxide dismutase [SOD]), and IAF area were recorded. All subjects were assigned into 3 groups according to body mass index (BMI): obese group (BMI ≥ 28 kg/m, 43 subjects), overweight group (24 ≤ BMI < 28 kg/m, 46 subjects), and control group (BMI < 24 kg/m, 47 subjects). Then, statistical analysis was performed.There were significant differences in IAF area, leptin, adiponectin, 8-iso-PGF2α, MDA, SOD, fasting insulin (FINS), fasting blood glucose (FBG), and homeostasis model assessment-insulin resistance (HOMA-IR) among these 3 groups (P < .05). Male subjects in the obese group had higher leptin, 8-iso-PGF2α, MDA, FINS, and HOMA-IR levels, compared to subjects in the overweight and control groups. Furthermore, subjects in the overweight group had a larger IAF area and higher 8-iso-PGF2α, MDA, and FBG levels, when compared to controls. In addition, SOD was significantly lower in the obese and overweight groups than in the control group. However, there were no statistical differences in age, systolic and diastolic blood pressure, lipids, and islet β-cell secretion function (homeostasis model assessment-β) among these 3 groups (P ≥ .05). Moreover, the IAF area was positively correlated to 8-iso-PGF2α and MDA, and negatively correlated to SOD.Oxidative stress is significantly associated with the IAF area in obese males, and abdominal obesity could increase oxidative stress level and insulin resistance.

Topics: Adiponectin; Adult; Blood Glucose; Body Mass Index; Dinoprost; Humans; Insulin Resistance; Intra-Abdominal Fat; Leptin; Male; Malondialdehyde; Middle Aged; Obesity; Oxidative Stress; Superoxide Dismutase; Young Adult

Active glucocorticoid levels are elevated in the adipose tissue of obesity due to the enzyme 11 beta-hydroxysteroid dehydrogenase type 1. Glucocorticoids can bind and activate both glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), and pharmacological blockades of MR prevent high-fat diet-induced obesity and glucose intolerance. To determine the significance of MR in adipocytes, we generated adipocyte-specific MR-knockout mice (AdipoMR-KO) and fed them high-fat/high-sucrose diet. We found that adipocyte-specific deletion of MR did not affect the body weight, fat weight, glucose tolerance or insulin sensitivity. While liver weight was slightly reduced in AdipoMR-KO, there were no significant differences in the mRNA expression levels of genes associated with lipogenesis, lipolysis, adipocytokines and oxidative stress in adipose tissues between the control and AdipoMR-KO mice. The results indicated that MR in mature adipocytes plays a minor role in the regulation of insulin resistance and inflammation in high-fat/high-sucrose diet-induced obese mice.

Topics: Adipocytes; Adipokines; Adipose Tissue; Animals; Body Weight; Diet, High-Fat; Dinoprost; Lipid Metabolism; Liver; Male; Metabolic Syndrome; Mice, Knockout; Obesity; Primary Cell Culture; Receptors, Mineralocorticoid; RNA, Messenger; Sucrose; Triglycerides

To evaluate glycemic variability (GV) and oxidative stress in patients who achieved type 2 diabetes (T2DM) remission after bariatric surgery (BS).. Remission of T2DM after BS is characterized by high GV and high oxidative stress in the face of fasting blood glucose and HbA1c within the normal range.

Topics: Adult; Biomarkers; Blood Glucose; Case-Control Studies; Chi-Square Distribution; Diabetes Mellitus, Type 2; Dinoprost; Energy Intake; Female; Gastrectomy; Gastric Bypass; Glycated Hemoglobin; Humans; Insulin; Linear Models; Male; Middle Aged; Obesity; Oxidative Stress; Remission Induction; Time Factors; Treatment Outcome

Purpose - to improve antihypertensive therapy on the basis of studying the antioxidant properties of an angiotensin-converting enzyme (ACE) inhibitor (fosinopril sodium) and a diuretic (hydrochlorothiazide), their impact on endothelial dysfunction and pro-inflammatory cytokines activity in hypertensive patients with overweight and obesity. A combination of fosinopril sodium 20 mg/day and hydrochlorothiazid 12.5 mg/day was prescribed to 54 patients with essential hypertension of 1-3 grades, 30 to 65 years old . The control group included 10 healthy subjects matched for age and sex. During the course of combined antihypertensive therapy we observed a significant decrease of i-NOS activity, reduce of TNF-α type I of its soluble receptor (sTNF-αRI), and 8-iso-PgF2α in the patients. Activity of e-NOS, superoxide dismutase and catalase, in contrast, were increased in patients with hypertension and concomitant obesity. Thus, the improvement of endothelial function, a significant decrease autoimmune activation due to lower tension of oxidative stress in the examined patients optimizes use of a combination of fosinopril sodium and hydrochlorothiazid for differentiated therapy in hypertensive patients with obesity.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Case-Control Studies; Dinoprost; Diuretics; Drug Therapy, Combination; Endothelium, Vascular; Essential Hypertension; Female; Fosinopril; Humans; Hydrochlorothiazide; Male; Middle Aged; Nitric Oxide Synthase Type II; Obesity; Overweight; Receptors, Tumor Necrosis Factor, Type I; Tumor Necrosis Factor-alpha

Oxidative stress has been linked to many obesity-related conditions among children including cardiovascular disease, diabetes mellitus and hypertension. Exposure to environmental chemicals such as phthalates, ubiquitously found in humans, may also generate reactive oxygen species and subsequent oxidative stress. We examined longitudinal changes of 8-isoprostane urinary concentrations, a validated biomarker of oxidative stress, and associations with maternal prenatal urinary concentrations of phthalate metabolites for 258 children at 5, 9 and 14 years of age participating in a birth cohort residing in an agricultural area in California. Phthalates are endocrine disruptors, and in utero exposure has been also linked to altered lipid metabolism, as well as adverse birth and neurodevelopmental outcomes. We found that median creatinine-corrected 8-isoprostane concentrations remained constant across all age groups and did not differ by sex. Total cholesterol, systolic and diastolic blood pressure were positively associated with 8-isoprostane in 14-year-old children. No associations were observed between 8-isoprostane and body mass index (BMI), BMI Z-score or waist circumference at any age. Concentrations of three metabolites of high molecular weight phthalates measured at 13 weeks of gestation (monobenzyl, monocarboxyoctyl and monocarboxynonyl phthalates) were negatively associated with 8-isoprostane concentrations among 9-year olds. However, at 14 years of age, isoprostane concentrations were positively associated with two other metabolites (mono(2-ethylhexyl) and mono(2-ethyl-5-carboxypentyl) phthalates) measured in early pregnancy. Longitudinal data on 8-isoprostane in this pediatric population with a high prevalence of obesity provides new insight on certain potential cardiometabolic risks of prenatal exposure to phthalates.

Topics: Adolescent; Adult; Child; Child, Preschool; Dinoprost; Female; Humans; Longitudinal Studies; Male; Maternal Exposure; Mexican Americans; Obesity; Phthalic Acids; Pregnancy; Prenatal Exposure Delayed Effects; Prevalence; United States; Vasoconstrictor Agents

Metabolic syndrome has become an important health problem, which involves obesity, hyperlipidemia, insulin resistance, and high blood pressure values. The components of metabolic syndrome are all suggested as independent cardiovascular disease risk factors along with high mortality and morbidity rates accompanied by many organ and system complications.. We aimed to determine 8-isoprostane (8-IsoP) and coenzyme Q10 (CoQ10) levels in patients with metabolic syndrome and healthy individuals and demonstrate whether there was any relation between these parameters and metabolic syndrome criteria.. A total of 30 patients (10 male, 20 female) with metabolic syndrome and 20 age-matched healthy individuals (9 male, 11 female) were involved in the study. Body mass index, waist and hip circumferences, systolic and diastolic blood pressures and serum glucose, triglyceride, total cholesterol, high-density lipoprotein cholesterol, insulin, HbA1c, 8-IsoP and CoQ10 levels, and homeostasis model assessment of insulin resistance indexes of all participants were determined.. 8-IsoP levels were significantly increased in metabolic syndrome compared to healthy individuals (P = 0.003), however, there was no significant difference between groups for CoQ10 levels. 8-IsoP levels were positively correlated with waist circumference (r = 0.303, P = 0.032), diastolic blood pressure (r = 0.337, P = 0.017), systolic blood pressure (r = 0.329, P = 0.020) values and total cholesterol levels (r = 0.354, P = 0.012).. We can suggest that the levels of 8-IsoP, which is an indicator of the oxidative stress, increase in metabolic syndrome and this can be associated with high blood pressure and visceral adiposity, which are the components of metabolic syndrome.

Topics: Adult; Aged; Blood Pressure; Body Mass Index; Case-Control Studies; Dinoprost; Female; Humans; Insulin Resistance; Intra-Abdominal Fat; Male; Metabolic Syndrome; Middle Aged; Obesity; Triglycerides; Ubiquinone; Waist Circumference

The study was aimed to assess paraoxonase-1 (PON1) activity, pleiotropic effects of simvastatin, and its relationship to Q192R and M55L polymorphisms in obese and non-obese subjects with stable coronary artery disease (CAD).. The study included 53 subjects (22 obese) aged from 35 to 65 years with CAD. The control group consisted of 53 (18 obese) police officers without CAD. Patients with CAD were treated with simvastatin 40 mg/day for 12 months. The lipid profile, flow mediated dilation (FMD), intima media-thickness (IMT), fibrinogen, hs-CRP, TNF-α, urine 8-iso-PGF2α, and PON1 activity were evaluated in definite time points. PON1 polymorphisms were assessed at baseline in all observed individuals.. The patients with CAD and obesity presented at baseline significantly increased hs-CRP level, insignificantly decreased FMD and lower PON1 activity compared to non-obese individuals. There was no association of obesity with 8-iso-PGF2α in the CAD and control group. The PON1 activity was significantly higher in 192R carriers in patients and controls, irrespective of obesity. Obesity was not associated with the effects of simvastatin on PON1 activity, urine 8-iso-PGF2α, and TNF-α, whereas it blunted its effect on the FMD improvement. The Q192R polymorphism was associated with simvastatin effectiveness on hs-CRP and FMD.. Obesity and Q192R PON1 polymorphism are significantly associated with pleiotropic effects of simvastatin therapy in patients with stable CAD.

Topics: Adult; Aged; Aryldialkylphosphatase; C-Reactive Protein; Coronary Artery Disease; Dinoprost; Female; Humans; Male; Middle Aged; Obesity; Polymorphism, Single Nucleotide; Simvastatin; Tumor Necrosis Factor-alpha

Oxidative stress has been implicated in the pathogenesis of many conditions, including insulin resistance and obesity. However, in vivo data concerning these relationships are scarce and conflicting. Therefore, the aim of this study was to investigate the association of oxidative stress with abdominal adiposity and insulin resistance in individuals at high cardiometabolic risk.. A total of 116 overweight/obese individuals participating in the HealthGrain and Etherpaths European Projects, having waist circumference (WC) and any other component of the metabolic syndrome, were included in this cross-sectional evaluation. 8-Isoprostane concentrations in 24-hr urine were measured as marker of oxidative stress in vivo. Baseline anthropometric and metabolic parameters were analyzed according to quartiles of 8-isoprostanes. Linear regression (LR) analysis was used to assess clinical correlates of oxidative stress.. Urinary 8-isoprostane levels were 52% higher in men than in women (P<0.001). Across the isoprostanes quartiles, there was a significant increase in WC and body weight [P for trend<0.001; analysis of variance (ANOVA) P<0.001] and fasting triglycerides (P for trend<0.05; ANOVA P<0.05), and a significant decrease in high-density lipoprotein cholesterol (P for trend<0.001; ANOVA P=0.001). No significant association between urinary isoprostane concentrations and insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)] was found. WC circumference and body weight remained significant after adjustment for age and gender (P=0.023 and P=0.014, respectively) and independently associated with isoprostanes at LR (P<0.005 for both).. Central obesity was independently associated with oxidative stress even in a population homogeneous for adiposity and cardiometabolic risk, whereas no relationship was observed between oxidative stress and insulin resistance.

Topics: Abdominal Fat; Adiposity; Adult; Age Factors; Aged; Body Weight; Cholesterol, HDL; Cross-Sectional Studies; Dinoprost; Female; Humans; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Obesity; Overweight; Oxidative Stress; Risk Assessment; Sex Characteristics; Triglycerides; Waist Circumference

The aim of this study was to determine the effect of six-month-long physical exercise programme with a two-time exposure to whole-body cryostimulation (WBC) in 20 sessions on antioxidant enzyme activities, lipid profile, and body composition changes in obese people (30 adult subjects; BMI = 30.39 ± 4.31 kg/m(2)). Blood samples were taken before the programme, one month following the exercise programme, before and after the first WBC treatment, six months following the exercise programme, after the second WBC treatment, and finally one month after the intervention. Six months of moderate aerobic activity combined with WBC did not change body mass or fat and lean body mass percentages, or circulating adiponectin, leptin, and resistin concentrations. In response to intervention a significant decrease in the level of low-density lipoprotein and triglycerides was observed, with a slight increase in high-density lipoprotein concentration. The nature of changes in the activity of respective antioxidant enzymes was not identical. After one month of increased physical activity, a significant decrease in superoxide dismutase, catalase, and glutathione reductase activities was observed (13%, 8%, and 70%, resp.). The SOD activity increased significantly after successive whole-body cryostimulation sessions. As regards catalase, a significant progressive decrease in its activity was observed.

Topics: Adipokines; Adiponectin; Adult; Body Composition; Body Mass Index; Catalase; Cryotherapy; Dinoprost; Exercise Therapy; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Humans; Leptin; Lipids; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Obesity; Overweight; Resistin; Superoxide Dismutase; Triglycerides

Chronic oxidative stress is one of the key mechanisms responsible for disease progression in non-alcoholic fatty liver disease. However, so far, few studies reported increased circulating levels of oxidative stress markers in patients with non-alcoholic fatty liver and no study has been performed with newer markers of systemic oxidative stress. The aim was to assess the relationship between urinary 8-iso-prostaglandin F2α and serum soluble NOX2-derived peptide and the severity of liver steatosis in subjects with non-alcoholic fatty liver.. The study was performed in 264 consecutive patients referred for suspected metabolic disease. Steatosis was defined according to Hamaguchi ultrasonographic criteria. Oxidative stress was assessed by urinary 8-iso- prostaglandin F2α and serum soluble NOX2-derived peptide levels.. Patients with non-alcoholic fatty liver had higher (p < 0.001) mean values of urinary 8-iso-PGF2α and of serum soluble NOX2-derived peptide, alanine aminotransferase, Cytokeratin-18 and homeostasis model of insulin resistance and lower values of serum adiponectin as compared to those without. Prevalence of metabolic syndrome and of its clinical features was significantly higher in patients with non-alcoholic fatty liver. Same findings were also observed after the exclusion of obese subjects, or subjects with diabetes or with metabolic syndrome and in those not taking statin medication. In addition, the levels of urinary 8-iso-PGF2α were independent predictors of non-alcoholic fatty liver and a strong association of urinary 8-iso-PGF2α and of serum soluble NOX2-derived peptide with the severity of steatosis at ultrasound was also observed.. We demonstrated increased markers of oxidative stress in subjects with non-alcoholic fatty liver. Urinary 8-iso-PGF2α and serum soluble NOX2-derived peptide levels were independent from obesity, diabetes and metabolic syndrome and increased with the severity of liver steatosis at ultrasound.

Topics: Adult; Aged; Biomarkers; Case-Control Studies; Cohort Studies; Diabetes Mellitus; Dinoprost; Female; Humans; Linear Models; Male; Membrane Glycoproteins; Metabolic Syndrome; Middle Aged; NADPH Oxidase 2; NADPH Oxidases; Non-alcoholic Fatty Liver Disease; Obesity; Oxidative Stress; Severity of Illness Index; Ultrasonography

Piperidine-based peroxisome proliferator-activated receptor-α agonists are agents that are efficacious in improving lipid, glycemic, and inflammatory indicators in diabetes and obesity. This study sought to determine whether CP-900691 ((S)-3-[3-(1-carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl ester; CP), a member of this novel class of agents, by decreasing plasma triglycerides, could prevent diabetic nephropathy in the Black and Tan, BRachyuric (BTBR) ob/ob mouse model of type 2 diabetes mellitus. Four-week old female BTBR WT and BTBR ob/ob mice received either regular chow or one containing CP (3 mg/kg per day) for 14 weeks. CP elevated plasma high-density lipoprotein, albuminuria, and urinary excretion of 8-epi PGF(2α), a product of the nonenzymatic metabolism of arachidonic acid and whose production is elevated in oxidative stress, in BTBR WT mice. In BTBR ob/ob mice, CP reduced plasma triglycerides and non-esterified fatty acids, fasting blood glucose, body weight, and plasma interleukin-6, while concomitantly improving insulin resistance. Despite these beneficial metabolic effects, CP had no effect on elevated plasma insulin, 8-epi PGF(2α) excretion, and albuminuria, and surprisingly, did not ameliorate the development of diabetic nephropathy, having no effect on the accumulation of renal macrophages, glomerular hypertrophy, and increased mesangial matrix expansion. In addition, CP did not increase plasma high-density lipoprotein in BTBR ob/ob mice, while paradoxically increasing total cholesterol levels. These findings indicate that 8-epi PGF(2α), possibly along with hyperinsulinemia and inflammatory and dysfunctional lipoproteins, is integral to the development of diabetic nephropathy and should be considered as a potential target of therapy in the treatment of diabetic nephropathy.

Topics: Albuminuria; Animals; Anti-Obesity Agents; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dinoprost; Disease Progression; Female; Glomerular Mesangium; Hypercholesterolemia; Hypertriglyceridemia; Hypertrophy; Hypoglycemic Agents; Hypolipidemic Agents; Insulin Resistance; Kidney; Mice; Mice, Inbred Strains; Mice, Obese; Obesity; Piperidines; PPAR alpha; Propionates

Obesity-induced oxidative stress and inflammation are involved in the pathogenesis of cardiovascular disease. We investigated whether diet-induced, long-term, mild weight loss improved proinflammatory cytokine levels, leukocyte count, and oxidative stress. Overweight/obese participants (25 ≤ body mass index < 34 kg/m(2), N = 122, 30-59 years) joined a 3-year-long clinical intervention involving daily 100-kcal calorie deficits. Successful weight loss was defined as a reduction in initial body weight equal to 2 kg after the clinical intervention period. Body weight in the successful mild weight loss group (SWL, n = 50) changed 5.4% (-4.16 ± 0.31 kg) compared to 0.05 ± 0.14 kg in the unsuccessful weight loss group (n = 49). After 3 years, SWL participants exhibited significantly reduced insulin, triglycerides, total and low-density lipoprotein cholesterol, free fatty acids, and leukocyte count (P = .030). Furthermore, in the SWL group, serum interleukin (IL)-1β, IL-6, and urinary 8-epi-prostaglandin (PG)F2α were significantly reduced (45%, 30%, and 14%, respectively). In contrast, the unsuccessful weight loss group exhibited significant increases in percentage of body fat, waist circumference, oxidized low-density lipoprotein, and tumor necrosis factor-α, as well as a significant decrease in high-density lipoprotein cholesterol. After adjusting for baseline values, the 2 groups demonstrated significantly different percentage of body fat, waist circumference, leukocyte count (P = .018), insulin, IL-6 (P = .031), IL-1β (P < .001), and tumor necrosis factor-α (P < .001), as well as urinary 8-epi-PGF2α (P = .036). A positive correlation existed between IL-1β and urinary 8-epi-PGF2α (r = 0.435, P < .001) and between changes in IL-6 and urinary 8-epi-PGF2α (r = 0.393, P < .001). Long-term mild weight loss reduces inflammatory cytokine levels, leukocyte counts, and oxidative stress and may reverse the elevated oxidative stress induced by inflammatory mediators in the overweight and obese.

Topics: Adiposity; Adult; Body Mass Index; Cytokines; Diet, Reducing; Dinoprost; Female; Humans; Inflammation; Insulin; Interleukin-1beta; Interleukin-6; Leukocyte Count; Lipids; Male; Middle Aged; Obesity; Overweight; Oxidative Stress; Tumor Necrosis Factor-alpha; Waist Circumference; Weight Loss

Although many obese individuals are normoglycemic and asymptomatic of cardiometabolic complications, this apparent healthy state may be a misnomer. Since heart failure is a major cause of mortality in obesity, we investigated the effects of heme-oxygenase (HO) on heart failure and cardiometabolic complications in obese normoglycemic Zucker-fatty rats (ZFs). Treatment with the HO-inducer, hemin, reduced markers of heart failure, such as osteopontin and osteoprotegerin, abated left-ventricular (LV) hypertrophy/fibrosis, extracellular matrix/profibrotic proteins including collagen IV, fibronectin, TGF-β1, and reduced cardiac lesions. Furthermore, hemin suppressed inflammation by abating macrophage chemoattractant protein-1, macrophage-inflammatory protein-1 alpha, TNF-α, IL-6, and IL-1β but enhanced adiponectin, atrial-natriuretic peptide (ANP), HO activity, insulin sensitivity, and glucose metabolism. Correspondingly, hemin improved several hemodynamic/echocardiographic parameters including LV-diastolic wall thickness, LV-systolic wall thickness, mean-arterial pressure, arterial-systolic pressure, arterial-diastolic pressure, LV-developed pressure, +dP/dt, and cardiac output. Contrarily, the HO-inhibitor, stannous mesoporphyrin nullified the hemin effect, exacerbating inflammatory/oxidative insults and aggravated insulin resistance (HOMA-index). We conclude that perturbations in insulin signaling and cardiac function may be forerunners to overt hyperglycemia and heart failure in obesity. Importantly, hemin improves cardiac function by suppressing markers of heart failure, LV hypertrophy, cardiac lesions, extracellular matrix/profibrotic proteins, and inflammatory/oxidative mediators, while concomitantly enhancing the HO-adiponectin-ANP axis.

Topics: Adiponectin; Animals; Atrial Natriuretic Factor; Blood Glucose; Chemokine CCL2; Dinoprost; Endothelin-1; Heart Failure; Heart Function Tests; Heart Ventricles; Heme Oxygenase (Decyclizing); Hemin; Hemodynamics; Inflammation; Insulin; Insulin Resistance; Macrophage Inflammatory Proteins; Macrophages; Metalloporphyrins; Myocytes, Cardiac; Obesity; Rats; Rats, Zucker; Risk Factors; Tumor Necrosis Factor-alpha; Ultrasonography; Up-Regulation

Oxidative stress is associated with obesity, metabolic syndrome and inflammation, suggesting it could be an early event in the pathology of chronic diseases. We tested the hypothesis that elevated levels of oxidative stress markers are associated with increased C-reactive protein (CRP) and that this is independent of obesity and insulin resistance.. This study was cross-sectional designed and nondiabetic postmenopausal women (n = 1821) with CRP levels ≤10 mg/l was enrolled. The CRP levels were categorized into quartiles from the lowest to the highest concentrations (Q1-Q4). The degree of insulin resistance was determined using the homoeostasis model assessment of insulin resistance (HOMA-IR). We measured oxidative stress using urinary 8-epi-prostaglandin F2α (8-epi-PGF2α) and plasma oxidized low-density lipoprotein (ox-LDL).. After adjustments for age and lifestyle habits, including smoking and drinking, we found higher body mass index (BMI) and HOMA-IR scores in Q2 and Q3 vs Q1. The Q4 BMI and HOMA-IR scores were higher than all other quartiles. The plasma ox-LDL was higher in Q4 than in Q1. Urinary 8-epi-PGF2α was higher in Q3 and Q4 than in Q1 or Q2. Urinary 8-epi-PGF2α positively correlated with CRP (r = 0·235, P < 0·001), whereas no correlation was found between ox-LDL and CRP. Multiple linear regression analyses of BMI and HOMA-IR showed that the association between urinary 8-epi-PGF2α and CRP levels remained significant (P < 0·001).. Oxidative stress measured by increased concentration of urine 8-epi-PGF2α is strongly associated with CRP levels. This finding was independent of obesity and insulin resistance in nondiabetic postmenopausal women.

Topics: Aged; Blood Glucose; Body Mass Index; C-Reactive Protein; Dinoprost; Female; Homeostasis; Humans; Insulin; Insulin Resistance; Linear Models; Lipoproteins, LDL; Middle Aged; Obesity; Oxidative Stress; Postmenopause; Risk Factors

The purpose of this study was to assess whether the metabolically healthy overweight/obese phenotype is associated with decreased oxidative stress compared with normal-weight individuals with metabolic syndrome (MetS).. Plasma oxidized LDL (ox-LDL) and urinary 8-epi-prostaglandin F2α (8-epi-PGF2α) were analyzed in a cross-sectional study of 1846 healthy postmenopausal women. Participants were classified by presence (n=569) or absence (n=1277) of MetS and by BMI (18.5-24.9kg/m(2)=normal weight, n=1254; ≥25kg/m(2)=overweight/obese, n=592). MetS was diagnosed with the modified National Cholesterol Education Program Adult Treatment Panel III criteria.. Compared to normal weight women with MetS (n=296), metabolically healthy overweight/obese women (n=319) showed lower blood pressure, triglyceride, and glucose and higher HDL cholesterol, adiponectin, and LDL particle size. Ox-LDL was higher in overweight/obese women without MetS than in normal weight women without MetS (n=958) but was lower than in women with MetS. Urinary 8-epi-PGF2α level was about 11% lower in women without MetS than in women with MetS. Normal weight women with MetS had greater odds of having ox-LDL (multivariate odds ratio [OR] 2.42, 95% CI: 1.65-3.55) and 8-epi-PGF2α (OR 1.49; CI: 1.03-2.14) levels in the top quartile compared to normal weight women without MetS after adjusting for age, drinking, smoking, total- and LDL-cholesterol, and high sensitivity C-reactive protein. Additionally, there was no significant correlation between ox-LDL and 8-epi-PGF2α.. The metabolically healthy overweight/obese phenotype was associated with a better overall metabolic profile and less oxidative stress than that observed in normal weight individuals with MetS. Furthermore, there was a lack of association between ox-LDL and 8-epi-PGF2α.

Topics: Adiponectin; Aged; Anthropometry; Blood Glucose; Blood Pressure; Body Mass Index; Cholesterol, HDL; Cross-Sectional Studies; Dinoprost; Fatty Acids, Nonesterified; Female; Follicle Stimulating Hormone; Humans; Leukocyte Count; Life Style; Lipoproteins, LDL; Metabolic Syndrome; Middle Aged; Obesity; Overweight; Oxidative Stress; Postmenopause; Triglycerides

Secreted frizzled-related protein 5 (Sfrp5) has been described as novel adipokine in mice with insulin-sensitising and anti-inflammatory properties similar to adiponectin. The aim of this study was to compare serum concentrations and determinants of Sfrp5, its pro-inflammatory antagonist wingless-type MMTV integration site family member (Wnt)5a and adiponectin in humans and their regulation by coffee.. Serum concentrations of Sfrp5, Wnt5a and adiponectin were measured in 47 individuals who participated in a coffee intervention study. Associations with demographic, metabolic and immunological variables and regulation of serum levels by different amounts of daily coffee intake were analysed.. At baseline, fasting serum Sfrp5 levels ranged between 96 and 4056 ng/mL. Sfrp5 was directly correlated with a surrogate of insulin resistance (homeostasis model assessment of insulin resistance/HOMA-IR; r = 0·32, P < 0·05) and with the oxidative stress markers 8-isoprostane (r = 0·44, P < 0·01) and nitrotyrosine (r = 0·52, P < 0·001). Adiponectin showed inverse correlations with several indices of insulin resistance (e.g. HOMA-IR, Stumvoll index; all P < 0·05) and a direct correlation with the anti-atherogenic apolipoprotein A-I (r = 0·56, P < 0·001). Coffee did not affect serum concentrations of Sfrp5. Serum Wnt5a concentrations were below the detection limit (0·02 ng/mL) in 81% of the study participants.. In contrast to obese mouse models, serum Sfrp5 was directly related to HOMA-IR and oxidative stress in humans, but not with apolipoproteins, and thus, associations differed from those found for circulating adiponectin. These differences between Sfrp5 and adiponectin might be explained by differences in the investigated species.

Topics: Adaptor Proteins, Signal Transducing; Adiponectin; Animals; Body Mass Index; Clinical Trials as Topic; Coffee; Dinoprost; Eye Proteins; Humans; Insulin; Insulin Resistance; Membrane Proteins; Mice; Middle Aged; Models, Animal; Obesity; Oxidative Stress; Proto-Oncogene Proteins; Statistics as Topic; Tyrosine; Wnt Proteins; Wnt Signaling Pathway; Wnt-5a Protein

The assessment of oxidative stress may aid in the identification of subsequent metabolic risk in obese children. The objective of this study was to determine whether the plasma level of advanced oxidation protein products, analyzed with a recently proposed modified assay that involves a delipidation step (mAOPPs), was related to metabolic risk factors (MRFs) in severely obese children.. The plasma levels of mAOPPs were determined by spectrophotometry in 54 severely obese and 44 healthy children. We also measured lipid peroxidation biomarkers (thiobarbituric acid-reactive substances, malondialdehyde, and 8-isoprotane F(2α)) and sulfhydryl groups, a marker of antioxidant defense. Protein oxidation and lipid peroxidation markers were higher and sulfhydryl levels were lower in obese children compared with controls. Taking metabolic risk into account, obese children were subdivided according to the cutoff point (53.2 μmol/L) obtained for their mAOPPs values from the ROC curve. Anthropometric measures and the existence of hypertension did not differ between groups. The presence of dyslipidemia and insulin resistance was significantly higher in the group with higher mAOPPs levels. The highest levels of mAOPPs were found in the children with ≥3 MRFs. The level of mAOPPs was positively correlated with triglycerides and negatively correlated with high-density lipoprotein cholesterol. There was no correlation of this marker of protein oxidation with biomarkers of lipid peroxidation.. The determination of mAOPPs in delipidated plasma is an easy way to evaluate protein oxidation. It may be useful in severely obese children for better cardiovascular risk assessment.

Topics: Adolescent; Age of Onset; Biomarkers; Chi-Square Distribution; Child; Dinoprost; Dyslipidemias; Female; Humans; Hypertension; Insulin Resistance; Linear Models; Lipid Peroxidation; Lipids; Male; Malondialdehyde; Metabolic Syndrome; Obesity; Oxidation-Reduction; Oxidative Stress; Proteins; Risk Assessment; Risk Factors; Severity of Illness Index; Spain; Spectrophotometry; Sulfhydryl Compounds; Thiobarbituric Acid Reactive Substances; Up-Regulation

We compared the effects of tempol (300 μmol kg(-1) plus 300 μmol kg(-1) h(-1), n=14) and candesartan (10 μg kg(-1) plus 10 μg kg(-1) h(-1), n=14) on renal haemodynamics, excretory function, and responses to electrical stimulation of the renal nerves (RNS) in lean and obese rabbits under pentobarbitone anaesthesia. Depressor responses to tempol (-16 ± 2 mmHg) and candesartan (-12 ± 1 mmHg) were similar. Candesartan, but not tempol, significantly increased basal renal blood flow (RBF; +36 ± 7%). Tempol, but not candesartan, significantly reduced glomerular filtration rate (GFR; -30 ± 10%) and sodium excretion (U(Na)V; -44 ± 14%). RNS induced frequency-dependent reductions in RBF (-20 ± 3% at 1 Hz), GFR (-28 ± 6% at 1 Hz) and U(Na)V (-55 ± 6% at 1 Hz). Candesartan blunted these responses. Tempol did not significantly alter RBF and GFR responses to RNS but blunted the U(Na)V response. Responses to RNS, and the effects of tempol and candesartan, were similar in lean compared with obese rabbits. Unlike candesartan, tempol did not induce renal vasodilatation, maintain GFR and U(Na)V during reductions in arterial pressure, or blunt neurally-mediated vasoconstriction. In conclusion, unlike the AT(1)-receptor antagonist candesartan, tempol does not blunt the effects of RNS on renal haemodynamic function. Furthermore, under the current experimental conditions superoxide appears to make little contribution to the actions of endogenous angiotensin II on baseline renal haemodynamics or excretory function, or their responses to RNS.

Topics: Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Animals; Antioxidants; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Cyclic N-Oxides; Diet; Diet, High-Fat; Dinoprost; Dose-Response Relationship, Drug; Electric Stimulation; Heart Rate; Hematocrit; Kidney; Kidney Function Tests; Male; Obesity; Rabbits; Renal Circulation; Spin Labels; Superoxides; Tetrazoles; Urodynamics

To investigate the role of oxidative stress in pathogenesis of polycystic ovary syndrome (PCOS), especially in the obese PCOS.. 43 PCOS patients with BMI > or = 23 kg/m2 were grouped into PCOS1. 42 PCOS patients with BMI < 23 kg/m2 were grouped into PCOS2. Meanwhile, 85 infertility patients with normal endocrine function and body weight were grouped into control group. All patients were subjected to the measurement of serum levels of superoxide dismutase (SOD), 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) and visfatin. The difference among PCOS1, PCOS2 and control group were compared and the relationships between the indexes were analyzed with simple liner regression analysis.. The serum level of SOD in PCOS1 and PCOS2 were lower than that in the control group (P < 0.05), and the serum level of SOD in PCOS1 was lower than that in PCOS2 (P < 0.05). The serum levels of 8-iso-PGF2alpha and visfatin in PCOS1 were higher than those in PCOS2 and control group (P < 0.05). The serum levels of 8-iso-PGF2alpha and visfatin between PCOS2 and control group were not statistical different. In PCOS1 and PCOS2 groups, SOD activity decreased with increasing levels of 8-iso-PGF2alpha, the regression coefficient was -0.407. For serum vifation, there were positive correlations with both BMI and 8-iso-PGF2alpha, but negative correlation with SOD; the coefficients were 0. 402 (P = 0.008), 0.612 (P = 0.000), and -0.153 (P = 0.000), respectively. The indexes mentioned above did not have the liner relationship in the control group.. There was oxidative stress in PCOS patients, which was not obvious in the normal weight PCOS patients but quite severe in the obese PCOS patients.

Topics: Adolescent; Adult; Dinoprost; Female; Humans; Nicotinamide Phosphoribosyltransferase; Obesity; Oxidative Stress; Polycystic Ovary Syndrome; Regression Analysis; Superoxide Dismutase; Young Adult

To analyze the interplay among oxidative stress, NOX2, the catalytic core of nicotinamide-adenine dinucleotide phosphate oxidase, and endothelial dysfunction in children with obesity and/or hypercholesterolemia.. We performed a cross-sectional study comparing flow-mediated arterial dilation (FMD), oxidized low-density lipoprotein, and urinary excretion of isoprostanes (8-iso-PGF2α), as markers of oxidative stress, and NOX2 activity, as assessed by blood levels of soluble NOX2-dp (sNOX2-dp), in a population of 100 children, matched for age and sex, including 40 healthy subjects (HS), 20 children with hypercholesterolemia (HC), 20 obese children (OC), and 20 children with coexistence of hypercholesterolemia and obesity (HOC).. HOC had higher sNOX2-dp and oxidized low-density lipoprotein levels compared with HS, HC, and OC. HC, OC, and HOC had lower FMD values compared with HS. Urinary 8-iso-PGF2α excretion was higher in HOC compared with HS. FMD was inversely correlated with sNOX2-dp levels (r = -0.483; P < .001) and with the number of cardiovascular risk factors (r = -0.617; P < .001). Multiple linear regression analysis showed that the number of cardiovascular risk factors was the only independent predictive variable associated with FMD (β: -0.585; P < .001; R(2) = 35%) and sNOX2-dp (β: 0.587; P < .001; R(2) = 34%).. The study suggests that NOX2-generating oxidative stress may have a pathogenic role in the functional changes of the arterial wall occurring in HOC.

Topics: Adolescent; Biomarkers; Brachial Artery; Cardiovascular Diseases; Carotid Intima-Media Thickness; Case-Control Studies; Child; Cross-Sectional Studies; Dinoprost; Female; Humans; Hypercholesterolemia; Linear Models; Lipoproteins, LDL; Male; Membrane Glycoproteins; NADPH Oxidase 2; NADPH Oxidases; Obesity; Oxidative Stress; Risk Factors; Vasodilation

The receptor for advanced glycation end-products (RAGE) has been implicated in obesity-related metabolic disease and accelerated atherothrombosis.. We tested the hypothesis that changes in endogenous secretory (es)RAGE levels as a result of excess adiposity and oxidative stress may contribute to enhancing platelet activation in obese women, thus increasing the cardiovascular risk.. Eighty otherwise healthy obese women and 20 nonobese women were studied.. esRAGE and plasma adiponectin were reduced in obese women [median (interquartile range), 0.18 (0.13-0.26) vs. 0.38 (0.20-0.48) ng/ml, P = 0.003; and 4.4 (2.8-6.4) vs. 10.0 (6.9-12.5) μg/ml, P < 0.0001, respectively] who also displayed higher urinary 11-dehydro-thromboxane B(2) (11-dehydro-TXB(2)) [795 (572-1089) vs. 211 (135-301) pg/mg creatinine; P < 0.0001] and 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)) [544 (402-698) vs. 149 (98-219) pg/mg creatinine; P < 0.0001] compared to nonobese women. Direct correlations between plasma adiponectin and esRAGE (Rho = 0.43; P < 0.0001) and between urinary 8-iso-PGF(2α) and 11-dehydro-TXB(2) (Rho = 0.36; P = 0.001) were observed in obese women. Moreover, plasma esRAGE and urinary 11-dehdro-TXB(2) were inversely related (Rho = -0.29; P = 0.008). On multiple linear regression analysis, urinary 8-iso-PGF(2α) and plasma esRAGE were independent predictors of urinary 11-dehydro-TXB(2). In five obese women, a short-term weight loss program gave a significant increase in esRAGE and decrease in urinary 8-iso-PGF(2α) and 11-dehydro-TXB(2).. In otherwise healthy obese women, low plasma esRAGE levels are associated with reduced circulating adiponectin and enhanced thromboxane biosynthesis, which is in part mediated by increased lipid peroxidation. Thus, excess adiposity may be implicated in RAGE hyperactivation and thromboxane-dependent platelet activation, contributing to obesity-related metabolic and vascular disease.

Topics: Adiponectin; Adult; Anthropometry; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Dinoprost; Female; Humans; Linear Models; Lipid Peroxidation; Lipids; Middle Aged; Obesity; Oxidative Stress; Platelet Activation; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Risk; Thromboxane B2; Weight Loss

To evaluate whether oxidative stress is correlated with adiposity, obesity-related metabolic abnormalities, and ambulatory blood pressure (ABP) in a multi-ethnic pediatric population.. We conducted a prospective study enrolling 42 obese children (age, 12.8 ± 2.4 years) and 34 non-obese children (age, 11.8 ± 3.4 years). We measured urine 8-isoprostane and hydrogen peroxide (markers of oxidative stress) in both obese and non-obese groups. In the obese group, we measured the 24-hour ABP and obtained an oral glucose tolerance test, lipid panel, interleukin-6, and tumor necrosis factor-α.. 8-isoprostane and hydrogen peroxide were correlated with body mass index standard deviation score and waist circumference. The mean 8-isoprostane and hydrogen peroxide levels of the obese group were higher than those of the non-obese group. In the subset of obese subjects who underwent ABP monitoring, 8-isoprostane was correlated with mean 24-hour systolic blood pressure: within the obese group, 8-isoprostane was higher in obese children with elevated mean 24-hour systolic blood pressure.. Our findings provide evidence of a significant correlation between oxidative stress, adiposity, and blood pressure in children. Longitudinal studies in a larger population sample are needed to validate the association between elevated urine 8-isoprostane level and cardiovascular risk factors in an obese pediatric population.

Topics: Adolescent; Child; Cross-Sectional Studies; Dinoprost; Dyslipidemias; Female; Humans; Hydrogen Peroxide; Hypertension; Interleukin-6; Male; Obesity; Oxidative Stress; Prospective Studies; Tumor Necrosis Factor-alpha

Pentadecanoic acid (15:0) and heptadecanoic acid (17:0), the dairy-specific saturated fatty acids have been inversely, while inflammation and oxidative stress have been positively related to the risk of cardiovascular disease (CVD). Both fatty acid metabolism and inflammation and oxidative stress may be influenced by adiposity. In the current cross-sectional analyses among adolescents (mean age 15 years), we determined whether overweight status modified the associations between dairy fatty acids (pentadecanoic acid (15:0) and heptadecanoic acid (17:0)) represented in serum phospholipids (PL) and markers of inflammation and oxidative stress. Six biomarkers for inflammation and oxidative stress were analyzed, including circulating adiponectin, C-reactive protein (CRP), cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and urinary 15-keto-dihydro-PGF2α (15-keto) and 8-iso-PGF2α (F2-iso). Generalized linear regression analyses, adjusted for age, gender, race, tanner score, total energy intake and physical activity, revealed that PL dairy fatty acids were inversely associated with CRP, F2-iso and 15-keto in overweight, but not in normal weight adolescents (all P(interaction) < 0.05). However, higher level of PL dairy fatty acids was associated with lower IL-6 among all adolescents. Further adjustment for dietary intake of calcium, vitamin D, protein, total flavonoids, and ω-3 fatty acids did not materially change the findings. Dairy-specific saturated fats, i.e., 15:0 and 17:0 fatty acids, may contribute to the potential health benefits of dairy products, especially for overweight adolescents.

Topics: Adiposity; Adolescent; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Cross-Sectional Studies; Dairy Products; Dietary Fats; Dinoprost; Fatty Acids; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Linear Models; Male; Obesity; Oxidative Stress; Phospholipids; Risk Factors

Studies show that obese individuals have prolonged elevations in postprandial lipemia and an exacerbated inflammatory response to high fat meals, which can increase risk for cardiovascular diseases. As epidemiological studies indicate an association between type of fat and circulating inflammatory markers, the purpose of this study was to investigate the acute effect of different fat sources on inflammation and oxidative stress in overweight and obese individuals.. Eleven overweight and obese subjects consumed three high fat milkshakes rich in monounsaturated fat (MFA), saturated fat (SFA), or long-chain omega 3 polyunsaturated fat (O3FA) in random order. Blood samples collected at baseline, 1, 2, 4, and 6 hours postprandial were analyzed for markers of inflammation (soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor- α (TNF-α), and C-reactive protein (CRP)), oxidative stress (8-epi-prostaglandin-F2α (8-epi) and nuclear factor-κB (NF-κB)), and metabolic factors (glucose, insulin, non-esterified free fatty acids, and triglycerides (TG)).. O3FA enhanced NF-kB activation compared to SFA, but did not increase any inflammatory factors measured. Conversely, SFA led to higher ICAM-1 levels than MFA (p = 0.051), while MFA increased TG more than SFA (p < 0.05). CRP increased while TNF-α and 8-epi decreased with no difference between treatments.. While most of the inflammatory factors measured had modest or no change following the meal, ICAM-1 and NF-κB responded differently by meal type. These results are provocative and suggest that type of fat in meals may differentially influence postprandial inflammation and endothelial activation.

Topics: Adult; Biomarkers; Blood Glucose; Cross-Over Studies; Dairy Products; Dietary Fats; Dinoprost; Fatty Acids, Monounsaturated; Fatty Acids, Omega-3; Female; Humans; Inflammation; Intercellular Adhesion Molecule-1; Male; Middle Aged; NF-kappa B; Obesity; Overweight; Oxidative Stress; Postprandial Period; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1; Young Adult

The aim of this study was to determine the effect of the antioxidant vitamin E (VE) on adiponectin and leptin expression in obese rats. Thirty weaning male Sprague-Dawley rats were divided into three groups as follows: (1) a control group, fed with normal chow; (2) a diet-induced obesity group (DIO), fed with a high-fat diet and (3) an intervention group, fed with a high-fat diet supplemented with VE (350 mg/kg). After 10 weeks of being fed according to these group assignments, rats were weighed and euthanized. Blood and adipose tissues were then immediately collected; mRNA and protein levels of leptin and adiponectin were measured by realtime reverse transcription-polymerase chain reaction and Western blotting. Biomarkers of oxidative stress, including serum levels of 8-epi-prostaglandin-F(2)alpha (8-epi-PGF(2)alpha) and glutathione peroxidase activity, were also examined. Adiponectin and leptin levels were lower in the DIO group than in the control group. VE intervention increased the expression of both leptin and adiponectin (P values < 0.05). Association analysis showed that serum leptin levels correlated positively with body fat mass (r = 0.601, P < 0.05). Both serum leptin and adiponectin levels were associated with the presence of serum 8-epi-PGF2 alpha (leptin, r = 0.513, P < 0.05; adiponectin, r = -0.422, P < 0.05). Administration of VE decreases leptin and adiponectin expression in obese rats. This finding is consistent with the view that antioxidants can play an important role in the treatment of obesity-related diseases.

Topics: Adiponectin; Adipose Tissue; Animals; Antioxidants; Base Sequence; Biomarkers; Dietary Fats; Dinoprost; Disease Models, Animal; DNA Primers; Gene Expression; Glutathione Peroxidase; Leptin; Male; Obesity; Oxidative Stress; Rats; Rats, Sprague-Dawley; RNA, Messenger; Vitamin E; Weight Gain

Exercise can induce oxidative stress or an imbalance between reactive oxygen species and cellular antioxidant defenses.. We investigated the effect of a real-life exercise program on systemic oxidative stress measured by urinary concentrations of 8-isoprostaglandin F2alpha (8-iso-PGF2 alpha), a noninvasive index of lipid peroxidation, in a well-characterized pediatric group.. Healthy but primarily sedentary, 8- to 10-year-old children (n = 6, mean age 8.8 +/- 0.9 years) of equally distributed healthy weight, overweight, and obese categories, participated in a 5-week exercise program (track and field summer camp, 2 hours/day, 1-2 days/week).. By using high-performance liquid chromatography with online electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS), we found a significant (p = .028) increase in group mean urinary 8-iso-PGF2 alpha concentration from 8.163 +/- 6.919 ng/mg creatinine pre-exercise program to 32.320 +/- 16.970 ng/mg creatinine post-exercise program. The increase was also measured at each individual level. We found preliminary evidence that pre- and post-exercise program urinary 8-iso-PGF2 alpha concentrations selectively correlated with children's cardiometabolic characteristics and mood.. Our results warrant further exploration of the relationships between pre/post-exercise oxidative stress marker 8-iso-PGF2 alpha and cardiometabolic characteristics, exercise habits, eating habits, and mood to determine whether increased post-exercise oxidative stress in healthy children is part of their normal adaptation to exercise or mediator of oxidative injury.

Topics: Affect; Child; Creatinine; Dinoprost; Exercise; Exercise Therapy; Feasibility Studies; Female; Health Status; Humans; Lipid Peroxidation; Male; Obesity; Overweight; Oxidative Stress; Pilot Projects

The aim was to examine the role of cyclooxygenase (COX)-2-mediated inflammation in the development of obese linked insulin resistance and fatty liver. The rats were fed separately regular diet (CONT), high-fat diet (HFD) ad libitum, or energy restrictedly for 12 weeks. Rats fed HFD ad libitum were further divided into three subgroups co-treated with vehicle (HFa), or a selective COX-2 inhibitor celecoxib (HFa-Cel) or mesulid (HFa-Mes). Euglycemic hyperinsulinemic clamp (EHC) experiment was performed at the end of study. Another set of rats with similar grouping was further divided into those with a 4, 8, or 12-week intervention period for hepatic sampling. Body weight was increased significantly and similarly in HFa, HFa-Cel, and HFa-Mes. Time-dependent increases in plasma insulin, glucose, 8-isoprostanes, leptin levels, homeostasis model assessment of insulin resistance (HOMA-IR) and hepatic triglyceride contents shown in HFa were significantly reversed in HFa-Cel and HFa-Mes. During EHC period, the reduction in stimulation of whole body glucose uptake, suppression of hepatic glucose production and metabolic clearance rate of insulin shown in HFa were significantly reversed in HFa-Cel and HFa-Mes. The enhanced COX-2 and tumor necrosis factor-alpha (TNF-alpha) but attenuated PPAR-gamma and C/EBP-alpha mRNA expressions in epididymal fat shown in HFa were significantly reversed in HFa-Cel and HFa-Mes. The increases in average cell size of adipocytes and CD68 positive cells shown in HFa were also significantly reversed in HFa-Cel and HFa-Mes. Our findings suggest that COX-2 activation in fat inflammation is important in the development of insulin resistance and fatty liver in high fat induced obese rats.

Topics: Adipocytes; Adipogenesis; Adipose Tissue; Animals; Blood Glucose; Body Weight; Celecoxib; Cell Size; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Dinoprost; Disease Models, Animal; Fatty Liver; Insulin; Insulin Resistance; Leptin; Liver; Macrophages; Male; Membrane Proteins; Obesity; Panniculitis; Pyrazoles; Rats; Rats, Sprague-Dawley; Sulfonamides; Time Factors; Triglycerides; Tumor Necrosis Factor-alpha

Increased reactive oxygen species may exhaust the antioxidant capability of human defense systems, leading to oxidative stress and cancer development. Urinary F2-isoprostanes, secondary end products of lipid peroxidation, are more accurate markers of oxidative stress than other available biomarkers. No prospective study has investigated whether levels of 15-F(2t)-isoprostane (15-F(2t)-IsoP) and its metabolite 2,3-dinor-5,6-dihydro-15-F(2t)-IsoP (15-F(2t)-IsoPM) are related to breast cancer risk.. We conducted a nested case-control study within the Shanghai Women's Health Study, a population-based cohort study of 74,942 Chinese women between 40 and 70 years of age. Prediagnostic urinary 15-F(2t)-IsoP and 15-F(2t)-IsoPM were measured by gas chromatography mass spectrometry for 436 breast cancer cases and 852 individually matched controls.. Urinary excretion of isoprostanes was not significantly different between cases and controls. However, among overweight women, levels of isoprostanes were positively associated with breast cancer risk, which became stronger with increasing body mass index (BMI). Among women with a BMI > or = 29, the odds ratio (OR) increased to 10.27 (95% CI, 2.41 to 43.80) for the highest compared with the lowest tertile of 15-F(2t)-IsoPM (P for trend = .003; P for interaction = .0004). In contrast, 15-F(2t)-IsoP and 15-F(2t)-IsoPM were inversely associated with breast cancer risk among nonoverweight women. Among women with a BMI < or = 23, breast cancer risk was reduced with increasing 15-F(2t)-IsoP levels in a dose-response manner (P for trend = .006), with an OR of 0.46 (95% CI, 0.26 to 0.80) for the highest tertile versus the lowest (P for interaction = .006).. Our results suggest that the role of oxidative stress in breast cancer development may depend on adiposity.

Topics: Adult; Aged; Body Mass Index; Breast Neoplasms; Case-Control Studies; China; Dinoprost; Female; Humans; Middle Aged; Obesity; Oxidative Stress; Risk Factors; Women's Health

The aim of the present observational study was to investigate the relationships between glycaemic status and levels of oxidative stress and inflammation in well-controlled type 2 diabetes subjects. Metabolic variables (weight, BMI, waist circumference (waist), blood glucose, glycated Hb (HbA(1c)), insulin, blood lipids), biomarkers of oxidative stress (8-iso-PGF(2alpha), malondialdehyde, 8-oxo-7,8-dihydro-2'-deoxyguanosine, formamido pyrimidine glycosylase-sites, frequency of micronucleated erythrocytes, nitrotyrosine) and inflammatory markers (high sensitivity C-reactive protein (hsCRP), IL-6, cyclo-oxygenase-catalyzed PGF(2alpha)-metabolite) were measured. Fifty-six patients (thirty women and twenty-six men, age 62.3 (SD 7.0) years, HbA(1c) 6.1 (SD 0.9) %, BMI 28.3 (SD 3.8) kg/m(2), waist 99.6 (SD 11.1) cm) were included in the study. HbA(1c) (r 0.29, P=0.03) and blood glucose (r 0.33, P=0.01) correlated positively with 8-iso-PGF(2alpha). Positive correlations were also observed between HbA(1c) and nitrotyrosine (r 0.42, P=0.01), waist and hsCRP (r 0.37, P=0.005), hsCRP and IL-6 (r 0.61, P<0.0001) and between PGF(2alpha)-metabolite and 8-iso-PGF(2alpha) (r 0.27, P=0.048). The present study indicates that glycaemic status is associated with oxidative stress even in subjects with well-controlled type 2 diabetes. Furthermore, inflammation was more related to abdominal obesity than to glycaemic control. A large number of biomarkers of oxidative stress and inflammation were investigated, but only a few associations were found between the markers. This could be due to the fact that none of these biomarkers biosynthesises via similar pathways or simultaneously owing to their diverse nature and origin.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Biomarkers; Blood Glucose; Body Mass Index; C-Reactive Protein; Deoxyguanosine; Diabetes Mellitus, Type 2; Dinoprost; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inflammation; Insulin; Interleukin-6; Lipids; Male; Malondialdehyde; Middle Aged; Obesity; Oxidative Stress; Probability; Statistics, Nonparametric; Tyrosine; Waist Circumference

Obesity and systemic oxidative stress are closely related. However data concerning the relationships between oxidative stress and body fat mass distribution are sparse. Anthropometric and metabolic profile was evaluated in 148 clinically healthy middle-aged women to assess the correlations between oxidative stress, fat mass distribution, adipokines, and inflammatory markers. Systemic oxidative stress was assessed by urinary creatinine-indexed 8-epi-prostaglandin F-(2alpha) (8-epi-PGF(2alpha)). Body fat mass distribution was examined by dual-energy X-ray absorptiometry (DXA). Lipid profile, adipokines and inflammatory markers including leptin, adiponectin, high sensitive C-reactive protein (hsCRP), plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor-alpha (TNF-alpha) were determined. We found body mass index (BMI), waist circumference (WC), both central and peripheral DXA-derived regional fat mass (FM) accumulations were positively correlated with 8-epi-PGF(2alpha). Leptin, hsCRP and PAI-1also positively associated with 8-epi-PGF(2alpha). After adjustment for BMI and WC, lower-body FM, total FM and PAI-1 retained significant association with 8-epi-PGF(2alpha). Mutliple linear regression analyses indicated lower-body FM and PAI-1 were the two important predicators of 8-epi-PGF(2alpha). These results suggest that DXA-derived regional FM indices, especially low extremity adiposity, are more closely associated with systemic oxidative stress than indirect anthropometric indices. Positive associations between 8-epi-PGF(2alpha) and PAI-1, hsCRP, leptin support the notion that oxidative-stress-induced dysregulation of inflammation and adipokines may mediate the obesity-related metabolic derangement.

Topics: Absorptiometry, Photon; Adipokines; Adult; Analysis of Variance; Body Fat Distribution; Body Mass Index; Creatinine; Cross-Sectional Studies; Dinoprost; Female; Humans; Inflammation Mediators; Middle Aged; Obesity; Oxidative Stress; Regression Analysis; Statistics, Nonparametric

To evaluate the effect of vitamin E on the level of oxidative stress in diet-induced obese Sprague-Dawley rats.. Thirty weaning male rats were placed into three groups with 10 animals each: a control group with normal chow, a diet-induced obesity group (DIO) with high-fat diet, and an intervention group with high-fat diet supplemented with vitamin E (VE, 350 mg/kg). Blood and adipose tissue were collected from rats after 10 weeks. Biomarkers of oxidative stress were detected for plasma 8-epi-prostaglandin- F(2)alpha (8-epi-PGF(2)alpha), thiobarbituric acid-reactive substances (TBARS), total anti-oxidative capacity (TAOC), alpha-tocopherol, superoxide dismutase (SOD) activity, and glutathione peroxidase activity (GPx). Lipid and glucose metabolism parameters such as plasma glucose, insulin, and triacylglycerol (TG) were also analyzed.. After 10 weeks, all obese rats (both the DIO and VE groups) had higher plasma 8-epi-PGF(2alpha) and TBARS levels than the controls. Their plasma-adjusted alpha-tocopherol, SOD, and GPx activities were lower than the control levels but insulin was higher (p<0.01). The VE intervention increased plasma SOD, GPx, and T-AOC, and decreased 8-epi-PGF(2alpha) (p<0.05). VE intervention also decreased plasma glucose, insulin, and TG levels (p<0.05).. Increased oxidative stress could be an important target for the prevention of obesity-related diseases. Vitamin E has moderate effects for improvement of oxidative stress status and glucose metabolism in the animal model of diet-induced obesity.

Topics: Analysis of Variance; Animals; Antioxidants; Biomarkers; Blood Glucose; Dietary Fats; Dietary Supplements; Dinoprost; Disease Models, Animal; Glutathione Peroxidase; Insulin; Male; Obesity; Oxidative Stress; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Triglycerides; Vitamin E

To investigate the relationship between adipocytokines levels and oxidative stress in obese males.. The levels of 8-iso-prostaglandinF2alpha(8-iso-PGF2alpha), superoxide dismutase (SOD), malondialdehyde (MDA), adiponectin, leptin, restistin, TNF-receptors 1(TNF-R1), Interleukin-1beta(IL-1beta) and Interleukin-6(IL-6) were measured in obese men and normal controls.. The levels of 8-iso-PGF(2alpha), MDA, leptin, TNF-R1, IL-1beta and IL-6 was significantly higher than that normal controls (P<0.05, P<0.01). The levels of adiponectin and the activity of SOD decreased significantly in obese men.There was no significant difference in the restistin between obese men and normal controls. There was significantly positive correlation between 8-iso-PGF(2alpha) and body mass index (BMI) (r=0.54, P<0.05) in obese. A significantly negative correlation was found between 8-iso-PGF(2alpha) and adiponectin (r=-0.56, P<0.05) in obese subjects. The levels of leptin was negative correlated with body fat content(%)(r=-0.53, P<0.05) in obese subjects. A significant negative correlation was observed between the levels of adiponectin and LDL(r=-0.54, P<0.05), IL-6 (r=-0.41, P<0.05). In a multiple regression analysis model, the levels of adiponectin and IL-6 were the main determinants of the oxidative stress in obese men.. Changed concentration of adipocytokines was found in obese men. There are significantly correlation with between oxidative stress and adipocytokines.

Topics: Adipokines; Adiponectin; Adult; Blood Glucose; Dinoprost; Humans; Interleukin-1beta; Interleukin-6; Leptin; Male; Malondialdehyde; Multivariate Analysis; Obesity; Oxidative Stress; Regression Analysis; Superoxide Dismutase

Excessive fat deposition is the key feature in obesity, which is empowered by cytokines overproduction and stimulation of cell oxidative stress processes, but little is known about energy availability in the form of ATP and mitochondrial function in the obese subjects. Thus, the aim of this study was to evaluate the possible changes in energy metabolism after a 8-weeks balanced-hypocaloric diet in obese subjects by measuring the ATP-content in leukocytes, by assessing 2-keto[1-13C]isocaproate breath test (KICA-BT) parameters related to mitochondrial function and by analyzing inflammatory and oxidative stress biomarkers. All the recruited obese subjects (n = 19) lost body weight after dieting (-5.55 +/- 2.88%). The hypocaloric treatment induced a decrease in leptin levels and lipid peroxidation markers. Interestingly, the ATP content in blood leukocytes increased (49.9 +/- 32.5 vs 36.2 +/- 27.9 pmol/mg prot.; p < 0.05), while KICA tracer mitochondrial oxidation decreased (30.9 +/- 5.9 vs. 33.1 +/- 4.5 % 13C; p < 0.05) after weight loss. These results show that two minimally invasive methods were able to detect changes in mitochondrial function as induced by a hypocaloric diet, which is of great interest in order to understand oxidative processes associated with weight homeostasis as well as to establish newer anti-obesity therapeutic targets by using mitochondrial function markers in vivo.

Topics: Adenosine Triphosphate; Adult; Biomarkers; Breath Tests; C-Reactive Protein; Caloric Restriction; Dinoprost; Energy Metabolism; Female; Humans; Interleukin-6; Keto Acids; Leukocytes; Male; Malondialdehyde; Mitochondria; Obesity; Oxidative Stress; Weight Loss

1. The present study was performed to test the hypothesis that the reactive oxygen species (ROS)-angiotensinogen (AGT)-renin angiotensin system (RAS) axis is sequentially activated in the development of diabetic nephropathy in Zucker diabetic fatty (ZDF) obese rats. 2. Genetic pairs of male ZDF obese and control ZDF lean rats (n = 12 of each species) were killed every 3 weeks from 12 to 21 weeks of age (n = 6 at each time point). 3. The ZDF obese rats developed diabetes mellitus at 12 weeks. At that time, urinary excretion rates of 8-isoprostane were similar between the groups; however, urinary 8-isoprostane levels were significantly increased at 15 weeks in ZDF obese rats compared with controls (36 +/- 6 vs 15 +/- 2 ng/day, respectively). At 15 weeks, protein levels of cortical angiotensinogen were similar between groups; however, cortical angiotensinogen levels were significantly increased at 18 weeks in ZDF obese rats compared with controls (relative ratio of 2.32 +/- 0.21 vs 1.00 +/- 0.20, respectively). At 12 weeks, angiotensin (Ang) II-like immunoreactivity was similar between groups in both the glomeruli and tubules; however, AngII-like immunoreactivity was increased significantly at 21 weeks in ZDF obese rats compared with controls (relative ratios of 1.98 +/- 0.55 vs 1.00 +/- 0.03, respectively, for glomeruli and 1.58 +/- 0.16 vs 1.00 +/- 0.13, respectively, for tubules). Moreover, at 21 weeks, the desmin-positive area in the glomeruli (0.63 +/- 0.08 vs 0.22 +/- 0.05%) and Masson's trichrome stain-positive area in the interstitium (4.97 +/- 0.05 vs 3.18 +/- 0.41%) were significantly increased in ZDF obese rats compared with controls, even though these differences had not been observed earlier. 4. These data suggest that the sequential activation of the ROS-AGT-RAS axis plays an important role in the development of diabetic nephropathy in ZDF obese rats.

Topics: Angiotensinogen; Animals; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dinoprost; Male; Obesity; Rats; Rats, Zucker; Reactive Oxygen Species; Renin-Angiotensin System; Time Factors

Obesity is independently associated with increased cardiovascular risk. However, since established obesity clusters with various cardiovascular risk factors, configuring the metabolic syndrome, the early effects of obesity on vascular function are still poorly understood. The current study was designed to evaluate the effect of early obesity on coronary endothelial function in a new animal model of swine obesity. As to method, juvenile domestic crossbred pigs were randomized to either high-fat/high-calorie diet (HF) or normal chow diet for 12 wk. Coronary microvascular permeability and abdominal wall fat were determined by using electron beam computerized tomography. Epicardial endothelial function and oxidative stress were measured in vitro. Systemic oxidative stress, renin-angiotensin activity, leptin levels, and parameters of insulin sensitivity were evaluated. As a result, HF pigs were characterized by abdominal obesity, hypertension, and elevated plasma lysophosphatidylcholine and leptin in the presence of increased insulin sensitivity. Coronary endothelium-dependent vasorelaxation was reduced in HF pigs and myocardial microvascular permeability increased compared with those values in normal pigs. Systemic redox status in HF pigs was similar to that in normal pigs, whereas the coronary endothelium demonstrated higher content of superoxide anions, nitrotyrosine, and NADPH-oxidase subunits, indicating increased tissue oxidative stress. In conclusion, the current study shows that early obesity is characterized by increased vascular oxidative stress and endothelial dysfunction in association with increased levels of leptin and before the development of insulin resistance and systemic oxidative stress. Vascular dysfunction is therefore an early manifestation of obesity and might contribute to the increased cardiovascular risk, independently of insulin resistance.

Topics: Animals; Blood Pressure; Capillary Permeability; Coronary Vessels; Dietary Fats; Dinoprost; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelium, Vascular; Female; Hypertension; Intra-Abdominal Fat; Leptin; Lipids; Microcirculation; Nitric Oxide; Obesity; Oxidative Stress; Random Allocation; Superoxides; Swine; Tomography, X-Ray Computed; Vasoconstrictor Agents; Vasodilator Agents

To evaluate the levels of antioxidative indexes, lipid metabolism and glycometabolism in high fat diet-induced obese rats.. A rat model of high fat diet induced obesity was established by feeding weaning male Sprague-Dawley rats with high-fat diet for 10 weeks. plasma 8-epi-prostaglandin-F2 (8-epi-PGF2), alpha-tocopherol, superoxide dismutase activity (SOD), and glutathione peroxidase activity (GSH-Px) were detected. Parameters of lipid metabolism and glycometabolism were also tested by standard methods.. After 10 weeks, the high fat diet-induced obesity and lipid metabolism and glycometabolism disorders of obese rats (n = 10) were found. In the comparison with the control groups (n = 10), plasma 8-epi-PGF2 levels of obese rats were more higher, while plasma adjusted alpha-tocopherol (divided by plasma lipids), SOD and GSH-Px activities of obese rats were more lower.. Obesity induced by high-fat feeding involves increased oxidative stress and decreased antioxidant capacity.

Topics: alpha-Tocopherol; Animals; Dietary Fats; Dinoprost; Male; Obesity; Oxidative Stress; Random Allocation; Rats; Rats, Sprague-Dawley; Superoxide Dismutase

We examined the associations between intake of different types of dietary fat and plasma levels of oxidative stress and endothelial activation markers in men.. For that purpose, a complete physical and metabolic profile was assessed. Dietary habits of subjects were determined with a 3-d food record. We also measured fasting plasma 8-iso-prostaglandin F2alpha and oxidized low-density lipoprotein concentrations and soluble forms of vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), and E-selectin. All these measurements were performed with commercial enzyme-linked immunosorbent assay kits and standards.. We found that a high total dietary fat intake was associated with high plasma sICAM-1 (r = 0.40, P < 0.005), sVCAM-1 (r = 0.31, P < 0.05), and E-selectin (r = 0.28, P < 0.05) levels. We also found that in men matched for plasma triacylglycerol levels, those consuming a diet rich in total fat (>105 g/d, n = 21) were characterized by higher circulating levels of sICAM-1 (P < 0.05) and E-selectin (P < 0.05) compared with triacylglycerol-matched individuals with a low total dietary fat intake (<105 g/d, n = 21). However, no significant difference was noted in plasma oxidized low-density lipoprotein levels between groups. Further, we conducted multivariate analyses and found that saturated fatty acid intake was the only dietary variable after inclusion of other dietary variables that contributed to circulating sICAM-1 (P < 0.05) and sVCAM-1 (P < 0.05).. Our study suggests that high dietary fat consumption is associated with endothelial activation in men and that this detrimental effect is likely attributable to the saturated fatty acid content of the diet.

Topics: Adult; Biomarkers; Diet; Diet Records; Dietary Fats; Dinoprost; E-Selectin; Endothelial Cells; Enzyme-Linked Immunosorbent Assay; Humans; Hypertriglyceridemia; Intercellular Adhesion Molecule-1; Lipoproteins, LDL; Male; Multivariate Analysis; Obesity; Oxidative Stress; Vascular Cell Adhesion Molecule-1

There is evidence that acarbose reduces the risk for development of diabetes and cardiovascular complications. The mechanism underlying the vasculoprotective effect is however not known. We hypothesized that vasculoprotection observed by acarbose may be the consequence of a diminished generation of oxidative stress.. Lean and obese Zucker rats received a diet containing 10% sucrose for 7 days. A part of the rats was treated with acarbose (15 mg/kg/day in chow). Blood glucose, plasma insulin, lipid peroxides, and as a more specific marker of oxidative stress, 8-isoprostanes, were analyzed. As cellular markers of oxidative stress we determined the activities of mitochondrial aconitase and NADPH-oxidase in aorta, heart, and kidney. In addition, poly(ADP-ribose) polymerase activity (PARP) was measured in aorta.. Sucrose feeding of obese Zucker rats resulted in increased blood glucose levels, plasma insulin, lipid peroxides and 8-isoprostanes. Mitochondrial aconitase was reduced; the activities of NAPDH-oxidase and PARP were enhanced. Treatment of obese Zucker rats with acarbose largely prevented these changes, whereas it had no effect in lean sucrose fed rats.. Specifically in obese Zucker rats sucrose feeding is associated with an increased oxidative stress. The data provide IN VIVO evidence that mitochondria play a role in the generation of reactive oxygen species (ROS) in insulin resistant, hyperglycaemic states. Activation of PARP by ROS may be an important mediator of vascular dysfunction in insulin resistance. Treatment with acarbose is helpful to prevent the increase in oxidative stress and vascular dysfunction induced by hyperglycemia.

Topics: Acarbose; Aconitate Hydratase; Aging; Animals; Aorta; Dinoprost; Glucose Intolerance; Lipid Peroxidation; Lipid Peroxides; Male; Mitochondria; NADPH Oxidases; Obesity; Organ Specificity; Oxidative Stress; Poly(ADP-ribose) Polymerases; Rats; Rats, Zucker; Thinness

Thirty-four children were assessed for body composition, blood pressure, lipids, glucose tolerance, markers of insulin resistance, oxidative stress, and adipokines. Children were divided into 3 groups: (1) normal weight, (2) overweight but otherwise healthy, and (3) overweight with the metabolic syndrome. There were no differences among any of the groups for age or Tanner stage, and anthropometric variables were similar between the overweight and the overweight with the metabolic syndrome groups. Differences across groups were found for high-density lipoprotein cholesterol (P < .001), triglycerides (P < .01), fasting insulin (P < .001), homeostasis model assessment (P < .01), adiponectin (P < .05), leptin (P < .0001), C-reactive protein (P < .0001), interleukin 6 (P < .0001), and 8-isoprostane (P < .001). In children, oxidative stress and adipokine levels worsen throughout the continuum of obesity and especially in the presence of components of the metabolic syndrome. Overweight children with components of the metabolic syndrome may be at elevated risk for future cardiovascular disease.

Topics: Adiponectin; Adolescent; Biomarkers; Blood Glucose; Blood Pressure; Body Composition; C-Reactive Protein; Cardiovascular Diseases; Child; Cholesterol, HDL; Dinoprost; Female; Humans; Insulin; Insulin Resistance; Interleukin-6; Leptin; Male; Metabolic Syndrome; Minnesota; Obesity; Oxidative Stress; Risk Assessment; Risk Factors; Triglycerides

Topics: Adipose Tissue; Adult; Animals; Body Mass Index; Cardiovascular Diseases; Cholesterol; Dinoprost; Female; Humans; Mice; Middle Aged; NADPH Oxidases; Obesity; Oxidation-Reduction; Oxidative Stress; Plasminogen Activator Inhibitor 1; Reactive Oxygen Species

Oxidative stress and the gene expression at the transcriptional level of antioxidant enzymes were investigated in two models of diabetes in mice. We used KKAy mice as a model of obese insulin-resistant diabetes, and streptozotocin-induced diabetic mice (STZ mice) as a model of insulin-deficient diabetes. C57BL mice and saline-injected ICR mice were used as the respective non-diabetic controls. To assess oxidative damage, plasma malonedialdehyde (MDA), urine 8-isoprostane and 8-hydroxy deoxyguanosine (8-OHdG) were measured. The mRNA expression of antioxidant enzymes, superoxide dismutase 1 (SOD-1) and glutathione peroxidase 1 (GPx-1) in the kidney and heart were quantified using a real-time polymerase chain reaction. The KKAy mice demonstrated moderate hyperglycemia and hyperlipidemia, and the STZ mice showed severe hyperglycemia and hypolipidemia. The KKAy mice, but not the STZ mice, showed elevated plasma MDA relative to the non-diabetic controls. Urine 8-isoprostane and 8-OHdG in both diabetic mouse groups increased significantly. The urine oxidative stress markers in the severely hyperglycemic STZ mice were higher than those in the moderately hyperglycemic KKAy mice. Although GPx-1 and SOD-1 showed elevated mRNA expression in the KKAy mice in the kidney and heart, in the STZ mice they did not increase compared to the controls. The compensatory up-regulation of the mRNA expression of antioxidant enzymes may be impaired in the insulin-deficient severely hyperglycemic state.

Topics: Animals; Base Sequence; Diabetes Complications; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dinoprost; Disease Models, Animal; DNA Primers; Gene Expression Regulation, Enzymologic; Glutathione Peroxidase; Insulin Resistance; Kidney; Male; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Mutant Strains; Myocardium; Obesity; Superoxide Dismutase

To investigate the relationship between active ghrelin and oxidative stress in obese subjects.. We measured the plasma levels of free 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha), a reliable and systemic marker of oxidative stress) and the active form of ghrelin in 17 obese and 17 normal subjects. The biologically active forms of ghrelin were measured using a commercially available radio-immunoassay kit and free 8-epi-PGF(2alpha) was measured using an enzyme immunoassay kit.. The circulating level of active ghrelin was significantly decreased (20.4 +/- 2.6 vs 40.9 +/- 3.9 fmol/ml, P < 0.01) while that of 8-epi-PGF(2alpha) was significantly increased (61.5 +/- 9.6 vs 17.3 +/- 3.4 pg/ml, P < 0.01) in obese subjects compared with normal subjects. The plasma levels of active ghrelin and 8-epi-PGF(2alpha) were significantly correlated in obese (r = -0.507, P < 0.05) and in all (r = -0.577, P < 0.01) subjects. Multivariate analysis showed that the plasma levels of active ghrelin and 8-epi-PGF(2alpha) were significantly and independently correlated in all subjects (F = 7.888, P < 0.01).. There is an inverse correlation between circulating levels of active ghrelin and oxidative stress in obesity. Low circulating levels of active ghrelin may enhance oxidative stress and the process of atherosclerosis in obese subjects.

Topics: Adult; Blood Glucose; Blood Pressure; Body Composition; Cholesterol; Dinoprost; Female; Ghrelin; Humans; Insulin; Male; Multivariate Analysis; Obesity; Oxidative Stress; Peptide Hormones; Triglycerides

Topics: Blood Glucose; Body Mass Index; Body Weight; Dinoprost; Glucose Clamp Technique; Humans; Hyperinsulinism; Insulin Resistance; Japan; Male; Obesity; Oxidative Stress; Reference Values; Triglycerides

Oxidative stress is involved in the pathophysiology of atherosclerosis, diabetes mellitus, hypertension, obesity, and cigarette smoking, all of these being risk factors for coronary heart disease (CHD). We tested the hypothesis that risk factors of CHD are associated with abundant systemic oxidative stress.. We conducted a case-control study with 93 CHD patients and 93 control subjects frequency-matched by age and sex. Urinary excretion of the F2-isoprostane 8-iso-prostaglandin (PG) F2alpha and its major urinary metabolite, 2,3-dinor-5,6-dihydro-8-iso-PGF2alpha, were measured by gas chromatography-tandem mass spectrometry. Body mass index, systolic blood pressure, and C-reactive protein were elevated in CHD patients (P<0.01). Urinary 8-iso-PGF2alpha and 2,3-dinor-5,6-dihydro-8-iso-PGF2alpha also differed, from 77 (interquartile range, 61-101) to 139 (93-231) pmol/mmol creatinine and from 120 (91-151) to 193 (140-275) pmol/mmol in control subjects and case subjects, respectively (P<0.001). 8-iso-PGF2alpha and its metabolite were highly correlated (Spearman's rho=0.664, P<0.001). HDL cholesterol was diminished in CHD patients (P<0.001). All of these characteristics predicted CHD in univariate analysis. In a multivariate model, the odds ratios were increased only for 8-iso-PGF2alpha (> or =131 pmol/mmol, P<0.001) and C-reactive protein (>3 mg/L, P<0.01), ie, by 30.8 (95% CI, 7.7-124) and 7.2 (1.9-27.6), respectively. 8-iso-PGF2alpha was found to be a novel marker in addition to known risk factors of CHD, ie, diabetes mellitus, hypercholesterolemia, hypertension, and smoking. Urinary excretion of 8-iso-PGF2alpha correlated with the number of risk factors for all subjects (P<0.001 for trend).. 8-iso-PGF2alpha is a sensitive and independent risk marker of CHD.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Case-Control Studies; Comorbidity; Coronary Disease; Diabetes Mellitus; Dinoprost; Female; Gas Chromatography-Mass Spectrometry; Germany; Humans; Hypercholesterolemia; Hypertension; Male; Middle Aged; Obesity; Oxidative Stress; Risk Factors; Sensitivity and Specificity; Smoking

To determine the clinical conditions associated with systemic oxidative stress in a community-based cohort. Information regarding cardiovascular risk factors associated with systemic oxidative stress has largely been derived from highly selected samples with advanced stages of vascular disease. Thus, it has been difficult to evaluate the relative contribution of each cardiovascular risk factor to systemic oxidative stress and to determine whether such risk factors act independently and are applicable to the general population.. We examined 2828 subjects from the Framingham Heart Study and measured urinary creatinine-indexed levels of 8-epi-PGF2alpha as a marker of systemic oxidative stress. Age- and sex-adjusted multivariable regression models were used to assess clinical correlates of oxidative stress. In age- and sex-adjusted models, increased urinary creatinine-indexed 8-epi-PGF2alpha levels were positively associated with female sex, hypertension treatment, smoking, diabetes, blood glucose, body mass index, and a history of cardiovascular disease. In contrast, age and total cholesterol were negatively correlated with urinary creatinine-indexed 8-epi-PGF2alpha levels. After adjustment for several covariates, decreasing age and total/HDL cholesterol ratio, sex, smoking, body mass index, blood glucose, and cardiovascular disease remained associated with urinary 8-epi-PGF2alpha levels.. Smoking, diabetes, and body mass index were highly associated with systemic oxidative stress as determined by creatinine-indexed urinary 8-epi-PGF2alpha levels. The effect of body mass index was minimally affected by blood glucose, and diabetes and may suggest an important role of oxidative stress in the deleterious impact of obesity on cardiovascular disease.

Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; Comorbidity; Diabetes Mellitus; Dinoprost; F2-Isoprostanes; Female; Humans; Male; Middle Aged; Multivariate Analysis; Obesity; Oxidative Stress; Risk Factors; Sex Factors; Smoking

Topics: CD40 Ligand; Dinoprost; F2-Isoprostanes; Humans; Male; Middle Aged; Obesity; Platelet Activation; Weight Loss

To investigate the direct relationship of oxidative stress with obesity and insulin resistance in men, we measured the plasma levels of 8-epi-prostaglandin F2alpha (PGF2alpha) in 14 obese and 17 nonobese men and evaluated their relationship with body mass index; body fat weight; visceral, sc, and total fat areas, measured by computed tomography; and glucose infusion rate during a euglycemic hyperinsulinemic clamp study. Obese men had significantly higher plasma concentrations of 8-epi-PGF2alpha than nonobese men (P < 0.05). The plasma levels of 8-epi-PGF2alpha were significantly correlated with body mass index (r = 0.408; P < 0.05), body fat weight (r = 0.467; P < 0.05), visceral (r = 0.387; P < 0.05) and total fat area (r = 0.359; P < 0.05) in all (obese and nonobese) men. There was also a significant correlation between the plasma levels of 8-epi-PGF2alpha and glucose infusion rate in obese men (r = -0.552; P < 0.05) and all men (r = -0.668; P < 0.01). In all subjects, the plasma levels of 8-epi-PGF2alpha were significantly correlated with fasting serum levels of insulin (r = 0.487; P < 0.01). In brief, these findings showed that the circulating levels of 8-epi-PGF2alpha are related to adiposity and insulin resistance in men. Although correlation does not prove causation, the results of this study suggest that obesity is an important factor for enhanced oxidative stress and that this oxidative stress triggers the development of insulin resistance in men.

Topics: Adipose Tissue; Adult; Cholesterol; Dinoprost; F2-Isoprostanes; Humans; Insulin Resistance; Male; Obesity; Oxidative Stress

The mechanisms underlying the development of hypertension in obesity are not yet fully understood. We recently reported the development of hypertension in a rat model of diet-induced obesity. When Sprague-Dawley rats (n=60) are fed a moderately high fat diet (32 kcal% fat) for 10 to 16 weeks, approximately half of them develop obesity (obesity-prone [OP] group) and mild hypertension (158+/-3.4 mm Hg systolic pressure), whereas the other half (obesity-resistant [OR] group) maintains a body weight equivalent to that of a low fat control group and is normotensive (135.8+/-3.8 mm Hg). We examined the potential role of oxidative stress in the development of hypertension in this model. Lipid peroxides measured as thiobarbituric acid-reactive substances showed a significant increase in the LDL fraction of OP rats (2.8+/-0.32 nmol malondialdehyde/mg protein) compared with OR and control rats (0.9+/-0.3 nmol malondialdehyde/mg protein). Also, aortic and kidney thiobarbituric acid-reactive substances showed a significant (3- and 5- fold) increase in OP rats after 16 weeks of diet. In addition, superoxide generation by aortic rings, measured by lucigenin luminescence, showed a 2-fold increase in the OP group compared with both the OR and control groups. In addition, free isoprostane excretion and nitrotyrosine in the kidney showed an increase in OP rats only. The urine and plasma nitrate/nitrite measured by the LDH method showed a 1.8-fold decrease in OP rats compared with OR rats. However, endothelial NO synthase expression in the kidney cortex and medulla assessed by reverse transcriptase-polymerase chain reaction showed a strong increase in the OP rats versus OR and control rats (endothelial NO synthase/beta-actin ratio 1.3+/-0.04 in OP rats versus 0.44+/-0.02 in OR rats), suggesting a possible shift toward superoxide production by the enzyme. Collectively, the data show a decreased NO bioavailability in OP animals that is due in part to the increased oxidative stress.

Topics: Animals; Aorta, Thoracic; Blood Pressure; Body Weight; Dietary Fats; Dinoprost; Disease Models, Animal; F2-Isoprostanes; Hyperlipidemias; Hypertension; Kidney Cortex; Kidney Medulla; Lipid Peroxides; Male; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Obesity; Oxidative Stress; Rats; Rats, Sprague-Dawley; Renin; Thiobarbituric Acid Reactive Substances

We have concurrently investigated oxidant stress, glucose tolerance and glucose-stimulated insulin responses in the obese Zucker rat, a widely used model of insulin resistance. The plasma level of the lipid peroxidation product 8-epi-prostaglandin F2alpha, a sensitive in vivo marker of oxidant stress, was elevated approximately 5-fold in 13-week old obese relative to age-matched, insulin-sensitive lean Zucker rats. Supplementation of the diet with vitamin E (as (+)-alpha-tocopherol acetate, 0.5% w/w) for 4 weeks, reduced plasma 8-epi-prostaglandin F2alpha and concomitantly reversed glucose-stimulated hyperinsulinaemia in the obese Zucker rat without worsening glucose tolerance. We therefore provide evidence of oxidant stress, measured as elevated plasma 8-epi-prostaglandin F2alpha, for the first time in the obese Zucker rat which now provides a rationale for the beneficial effects of antioxidants on insulin action previously reported in this model of insulin resistance.

Topics: Animals; Blood Glucose; Body Weight; Dietary Supplements; Dinoprost; Hyperglycemia; Hyperinsulinism; Insulin; Insulin Resistance; Male; Obesity; Oxidative Stress; Rats; Rats, Zucker; Vitamin E