dinoprost and Metabolic-Syndrome

Prostaglandins are primary mediators of pain and are involved in pathological conditions such as hypertension, cancer and inflammation but are also needed for normal function of the female reproductive system. This may hold true for other systems because long term use of selective COX-2 inhibitors such as VIOXX and BEXTRA was associated with heart failure, leading to their withdrawal. A thorough study of the contribution of prostaglandins in the regulation of normal body function is clearly needed. A major drawback of the current therapeutic strategies aiming at controlling PGs is that they aim at early steps of biosynthesis thus blocking all PGs, good and bad. However, PGs often work as opposing dyads such as PGI2-TXA2 in the vascular system and PGF2alpha-PGE2 in the female reproductive system. The paradigm thus appears as effecting selective synthesis, transport and action of individual PG isoforms. In this respect, the female reproductive system appears as an ideal study model. Data from human and animal genome projects allowed identifying the corresponding members of the biosynthetic and signal transduction components of the PG system in different animal species. Of particular interest was that PG terminal synthase shared similarities or identity with enzymes previously known for steroid or sugar metabolism and free radical detoxification. We present here an integrated view of PG action based on observations in the female reproductive system, but with potential strategic implications for cardiovascular and metabolic complications.

Topics: Animals; Cyclooxygenase 1; Cyclooxygenase 2; Dinoprost; Dinoprostone; Female; Humans; Menstruation Disturbances; Metabolic Syndrome; Reproduction

The postprandial triglyceride-rich lipoprotein (TRL) concentration is a recognized independent cardiovascular disease risk factor. Diet is the natural approach for these postprandial alterations. Dietary polyphenols and long chain n-3 polyunsaturated fatty acids (LCn3s) are associated with a lower cardiovascular disease risk.. This randomized controlled study evaluated, in persons with a high risk of cardiovascular disease, the effects of diets naturally rich in polyphenols and/or marine LCn3s on plasma TRLs and urinary 8-isoprostane concentrations, a biomarker of oxidative stress.. According to a 2 × 2 factorial design, 86 overweight/obese individuals with a large waist circumference and any other component of the metabolic syndrome were randomly assigned to an isoenergetic diet 1) poor in LCn3s and polyphenols, 2) rich in LCn3s, 3) rich in polyphenols, or 4) rich in LCn3s and polyphenols. The diets were similar in all other components. Before and after the 8-wk intervention, fasting and postmeal TRLs and 8-isoprostane concentrations in 24-h urine samples were measured.. Dietary adherence was good in all participants. Polyphenols significantly reduced fasting triglyceride concentrations (2-factor ANOVA) in plasma (P = 0.023) and large very-low-density lipoproteins (VLDLs) (P = 0.016) and postprandial triglyceride total area under the curve in plasma (P = 0.041) and large VLDLs (P = 0.004). LCn3s reduced postprandial chylomicron cholesterol and VLDL apolipoprotein B-48. The concentrations of urinary 8-isoprostane decreased significantly with the polyphenol-rich diets. Lipoprotein changes induced by the intervention significantly correlated with changes in 8-isoprostane.. Diets naturally rich in polyphenols positively influence fasting and postprandial TRLs and reduce oxidative stress. Marine LCn3s reduce TRLs of exogenous origin. Through their effects on postprandial lipemia and oxidative stress, polyphenols may favorably affect cardiovascular disease risk.

Topics: Adult; Aged; Antioxidants; Biomarkers; Body Mass Index; Diet; Dinoprost; Dyslipidemias; Fasting; Fatty Acids, Omega-3; Female; Humans; Lipoproteins; Male; Metabolic Syndrome; Middle Aged; Overweight; Oxidative Stress; Polyphenols; Postprandial Period; Triglycerides

Subjects with the metabolic syndrome (MetS) have enhanced oxidative stress and inflammation. Dietary fat quality has been proposed to be implicated in these conditions. We investigated the impact of four diets distinct in fat quantity and quality on 8-iso-PGF2α (a major F2-isoprostane and oxidative stress indicator), 15-keto-13,14-dihydro-PGF2α (15-keto-dihydro-PGF2α, a major PGF2α metabolite and marker of cyclooxygenase-mediated inflammation) and C-reactive protein (CRP). In a 12-week parallel multicentre dietary intervention study (LIPGENE), 417 volunteers with the MetS were randomly assigned to one of the four diets: two high-fat diets (38 % energy (%E)) rich in SFA or MUFA and two low-fat high-complex carbohydrate diets (28 %E) with (LFHCC n-3) or without (LFHCC) 1·24 g/d of very long chain n-3 fatty acid supplementation. Urinary levels of 8-iso-PGF2α and 15-keto-dihydro-PGF2α were determined by RIA and adjusted for urinary creatinine levels. Serum concentration of CRP was measured by ELISA. Neither concentrations of 8-iso-PGF2α and 15-keto-dihydro-PGF2α nor those of CRP differed between diet groups at baseline (P>0·07) or at the end of the study (P>0·44). Also, no differences in changes of the markers were observed between the diet groups (8-iso-PGF2α, P = 0·83; 15-keto-dihydro-PGF2α, P = 0·45; and CRP, P = 0·97). In conclusion, a 12-week dietary fat modification did not affect the investigated markers of oxidative stress and inflammation among subjects with the MetS in the LIPGENE study.

Topics: Aged; Biomarkers; C-Reactive Protein; Diet, Fat-Restricted; Dietary Carbohydrates; Dietary Fats; Dietary Supplements; Dinoprost; Enzyme-Linked Immunosorbent Assay; Fatty Acids; Feeding Behavior; Female; Humans; Inflammation; Male; Metabolic Syndrome; Middle Aged; Oxidative Stress

The metabolic syndrome is associated with increased angiotensin II activity, induction of a proinflammatory and oxidative state, and endothelial dysfunction. We evaluated the ability of irbesartan, an angiotensin receptor blocker, and lipoic acid, an antioxidant, to affect endothelial function and inflammation in patients with the metabolic syndrome.. We randomized 58 subjects with the metabolic syndrome in a double-blinded manner to irbesartan 150 mg/d (n=14), lipoic acid 300 mg/d (n=15), both irbesartan and lipoic acid (n=15), or matching placebo (n=14) for 4 weeks. Endothelium-dependent and -independent flow-mediated vasodilation was determined under standard conditions. Plasma levels of interleukin-6, plasminogen activator-1, and 8-isoprostane were measured. After 4 weeks of therapy, endothelium-dependent flow-mediated vasodilation of the brachial artery was increased by 67%, 44%, and 75% in the irbesartan, lipoic acid, and irbesartan plus lipoic acid groups, respectively, compared with the placebo group. Treatment with irbesartan and/or lipoic acid was associated with statistically significant reductions in plasma levels of interleukin-6 and plasminogen activator-1. In addition, treatment with irbesartan or irbesartan plus lipoic acid decreased 8-isoprostane levels. No significant changes in blood pressure were noted in any of the study groups.. Administration of irbesartan and/or lipoic acid to patients with the metabolic syndrome improves endothelial function and reduces proinflammatory markers, factors that are implicated in the pathogenesis of atherosclerosis.

Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Antioxidants; Biomarkers; Biphenyl Compounds; Brachial Artery; Dietary Supplements; Dinoprost; Double-Blind Method; Drug Therapy, Combination; Endothelium, Vascular; Female; Humans; Inflammation; Interleukin-6; Irbesartan; Male; Metabolic Syndrome; Middle Aged; Plasminogen Activator Inhibitor 1; Tetrazoles; Thioctic Acid; Vasodilation

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

In this prospective study, we evaluated the association of retinoic acid (RA) with the metabolic syndrome (MetS) in the Chinese population.. A total of 1042 nondiabetic adults from the population-based Nutrition and Health of Aging Population were prospectively followed up for 4 years. Serum RA concentrations was determined and its relationship with the MetS and its component was investigated.. At baseline, higher RA levels were inversely associated with the presence of MetS (odds ratio 0.61; 95% confidence interval [CI] 0.44–0.74, P < .001) after adjustment for age, gender, body mass index, the homeostasis model assessment index for insulin resistance (HOMA-IR), and other confounding factors. Subjects with lower RA levels had a progressively worse cardiometabolic risk profile at baseline. Serum RA levels were inversely associated with 8-iso-prostaglandin F2α (P < .001), high-sensitivity C-reactive protein (P = .015), and IL-6 (P = .020) and positively correlated with high-density lipoprotein cholesterol (P = .038). Among 825 subjects without MetS at baseline, 146 had developed it at 4 years. Serum RA by quartiles was inversely correlated with the incident MetS (adjusted hazard ratio 0.67; 95% CI 0.48–0.81, P = .006). Apart from HOMA-IR (P < .001), the baseline RA level was the only independent predictor of the development of the MetS during the 4-year follow-up (odds ratio 0.53; 95% CI 0.40–0.69; P < .001) after adjustment for age, gender, body mass index, and HOMA-IR.. The serum RA level is inversely associated with the development of MetS independently of adiposity and insulin resistance.

Topics: Adiposity; Age Factors; Aged; Body Mass Index; C-Reactive Protein; Cholesterol, HDL; Dinoprost; Female; Follow-Up Studies; Health Surveys; Humans; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Prospective Studies; Sex Factors; Tretinoin

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

Adults with metabolic syndrome from different race/ethnicities are often predisposed to developing type 2 diabetes (T2D); however, growing evidence suggests that healthy diets and lifestyle choices can significantly slow or prevent progression to T2D. This poorly understood relationship to healthy dietary patterns and prevention of T2D motivated us to conduct a retrospective analysis to determine the potential impact of a minor dietary lifestyle change (daily mushroom consumption) on known T2D risk factors in racially diverse adults with confirmed features of the metabolic syndrome. Retrospectively, we studied 37 subjects who had participated in a dietary intervention focused on vitamin D bioavailability from white button mushrooms (WBM). All 37 had previously completed a 16-week study where they consumed 100 g of WBM daily and were then followed-up for one month during which no mushrooms were consumed. We analyzed differences in serum risk factors from baseline to 16-week, and from baseline to one-month follow-up. Measurement of serum diabetic risk factors included inflammatory and oxidative stress markers and the antioxidant component naturally rich in mushrooms, ergothioneine. Significant beneficial health effects were observed at 16-week with the doubling of ergothioneine from baseline, increases in the antioxidant marker ORAC (oxygen radical absorption capacity) and anti-inflammatory hormone, adiponectin and significant decreases in serum oxidative stress inducing factors, carboxymethyllysine (CML) and methylglyoxal (MG), but no change in the lipid oxidative stress marker 8-isoprostane, leptin or measures of insulin resistance or glucose metabolism. We conclude that WBM contain a variety of compounds with potential anti-inflammatory and antioxidant health benefits that can occur with frequent consumption over time in adults predisposed to T2D. Well-controlled studies are needed to confirm these findings and identify the specific mushroom components beneficial to health.

Topics: Adiponectin; Adult; Agaricus; Antioxidants; beta-Glucans; Biomarkers; Body Mass Index; Chitin; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Diet; Dinoprost; Ergothioneine; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Insulin Resistance; Leptin; Linear Models; Lysine; Male; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Oxidative Stress; Polyphenols; Pyruvaldehyde; Retrospective Studies; Risk Factors; Triglycerides; Vitamin D

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

To determine whether 8-iso-prostaglandin F2α (8-iso-PGF2α) is a reliable biomarker of the accumulation of metabolic risks [e.g., overweight, hypertension, impaired glucose tolerance (IGT), and dyslipidemia].. This was a cross-sectional study of the baseline characteristics of a Japanese general population cohort study: Research on Osteoarthritis/Osteoporosis Against Disability (ROAD). Of 1,690 participants, 1,527 fulfilled all questionnaires and examinations. Free and conjugated urinary 8-iso-PGF2α levels and metabolic syndrome (MetS) components including blood pressure, HbA1c, total cholesterol, high-density lipoprotein cholesterol (HDL-C), and non-HDL-C were analyzed. The data were analyzed by ANCOVA, multiple regression analysis, and multinomial logistic analysis.. 8-iso-PGF2α was significantly associated with HbA1c and significantly inversely associated with total cholesterol and non-HDL-C. Notably, IGT with an HbA1c cut-off of 5.5% was significantly associated with 8-iso-PGF2α level in participants aged ≤50 years. Multinomial logistic regression analysis revealed 8-iso-PGF2α level was significantly associated with a greater number of MetS risks present; this association was stronger in younger participants. In participants aged ≥71 years, 8-iso-PGF2α was significantly associated with a greater number of MetS risks with higher IGT cut-offs.. Urinary 8-iso-PGF2α can be a reliable marker of IGT and the accumulation of MetS risks, especially in younger people.

Topics: Adult; Aged; Biomarkers; Cardiovascular Diseases; Cohort Studies; Cross-Sectional Studies; Dinoprost; Female; Humans; Hypertension; Japan; Male; Metabolic Syndrome; Middle Aged; Oxidative Stress; Regression Analysis; Risk Factors; Waist Circumference

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

Identifying differences in plasma metabolic profiling between Lp-PLA2 279VV and 279FF in individuals without metabolic syndrome (MetS) can be used to elucidate the roles of novel Lp-PLA2 activities in normal physiological processes.. Non-MetS individuals with 279FF (n=36) and age-, sex- and BMI-matched VV subjects (n=36) were included in this analysis.. The FF subjects exhibited no appreciable enzyme activity. No significant differences were observed between the VV and FF subjects in the serum lipid profiles or hs-CRP, plasma ox-LDL, MDA or urinary 8-epi-PGF2α levels. The FF subjects also showed lower activities of lyso-phosphatidylcholine (lysoPC) (16:0) (p=0.003) and oleamide (p＜0.001) and a higher activity of L-tryptophan (p=0.016) than the VV subjects. In addition, the Lp-PLA2 activity positively correlated with the lysoPC (16:0) and lysoPC (18:0) activities and negatively correlated with the PC (16:0/22:6) and L-tryptophan activities in the VV subjects. Furthermore, in the VV subjects, the lysoPC (16:0) and lysoPC (18:0) activities negatively correlated with the presence of PCs containing 14:0/20:2, 14:0/22:4 and 16:0/22:6, while the oleamide activity exhibited a strong positive correlation with lysoPCs and a negative correlation with PCs, whereas the relationship between oleamide and lysoPCs and PCs was weaker in the FF subjects.. The present results indicate that the natural absence of the plasma Lp-PLA2 activity due to carriage of the Lp-PLA2 279FF genotype may reduce the generation of lysoPC (16:0) and oleamide and thereby enhance the activity of plasma tryptophan in normal physiological processes.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Adult; Alleles; Anthropometry; Blood Glucose; Blood Pressure; Body Mass Index; C-Reactive Protein; Dinoprost; Fatty Acids, Nonesterified; Female; Genotype; Humans; Lipids; Lipoproteins, LDL; Male; Malondialdehyde; Mass Spectrometry; Metabolic Syndrome; Metabolome; Phenotype; Risk Factors; Tryptophan

Because alterations in blood fatty acid (FA) composition by dietary lipids are associated with insulin resistance and related metabolic disorders, we hypothesized that serum phospholipid FA composition would reflect the early alteration of fasting glycemic status, even in people without metabolic syndrome (MetS). To examine this hypothesis, serum phospholipid FA, desaturase activities, fasting glycemic status, and cardiometabolic parameters were measured in study participants (n = 1022; 30-69 years; male, n = 527; female, n = 495; nondiabetics without disease) who were stratified into normal fasting glucose (NFG) and impaired fasting glucose (IFG) groups. Total monounsaturated FA (MUFA), oleic acid (OA; 18:1n-9), dihomo-γ-linolenic acid (DGLA; 20:3n-6), Δ-9-desaturase activity (D9D; 18:1n-9/18:0), and DGLA/linoleic acid (20:3n-6/18:2n-6) in serum phospholipids were significantly higher in IFG subjects than NFG controls. Study subjects were subdivided into 4 groups, based on fasting glucose levels and MetS status. Palmitoleic acid (16:1n-7) was highest in IFG-MetS and lowest in NFG-non-MetS subjects. Oleic acid and D9D were higher in IFG-MetS than in the other 3 groups. Dihomo-γ-linolenic acid and DGLA/linoleic acid were higher in MetS than in non-MetS, regardless of fasting glucose levels. The high-sensitivity C-reactive proteins (hs-CRPs) and 8-epi-prostaglandin-F2α were higher in IFG than in NFG, regardless of MetS status. Oxidized low-density lipoproteins were higher in IFG-MetS than in the other 3 groups. Total MUFAs, OA, and D9D were positively correlated with homeostasis model assessment of insulin resistance, fasting glucose, triglyceride, hs-CRP, and 8-epi-prostaglandin-F2α. Palmitoleic acid was positively correlated with triglyceride and hs-CRP. Lastly, total MUFA, OA, palmitoleic acid, and D9D were associated with early alteration of fasting glycemic status, therefore suggesting that these may be useful markers for predicting the risk of type 2 diabetes and cardiometabolic diseases.

Topics: 8,11,14-Eicosatrienoic Acid; Biomarkers; Blood Glucose; C-Reactive Protein; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dinoprost; Fasting; Fatty Acids, Monounsaturated; Female; Humans; Insulin; Insulin Resistance; Linoleic Acid; Lipoproteins, LDL; Male; Metabolic Syndrome; Middle Aged; Oleic Acid; Phospholipids; Stearoyl-CoA Desaturase; Triglycerides

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

We have previously shown nutritional intervention with fish oil (n-3 PUFA) to reduce numerous complications associated with the metabolic syndrome (MetS) in the JCR:LA-corpulent (cp) rat. In the present study, we sought to explore the potential role of fish oil to prevent glomerulosclerosis in JCR:LA-cp rats via renal eicosanoid metabolism and lipidomic analysis. Male lean and MetS JCR:LA-cp rats were fed a lipid-balanced diet supplemented with fish oil (5 or 10 % of total fat). After 16 weeks of feeding, albuminuria was significantly reduced in MetS rats supplemented with 5 or 10 % fish oil ( - 53 and - 70 %, respectively, compared with the untreated MetS rats). The 5 % fish oil diet resulted in markedly lower glomerulosclerosis ( - 43 %) in MetS rats and to a lesser extent in those supplemented with 10 % fish oil. Interestingly, untreated MetS rats had higher levels of 11- and 12-hydroxyeicosatetraenoic acids (HETE) v. lean rats. Dietary fish oil reduced these levels, as well as other (5-, 9- and 15-) HETE. Whilst genotype did not alter prostanoid levels, fish oil reduced endogenous renal levels of 6-keto PGF1α (PGI2 metabolite), thromboxane B2 (TxB2), PGF2α and PGD2 by approximately 60 % in rats fed 10 % fish oil, and TxB2 ( - 50 %) and PGF2α ( - 41 %) in rats fed 5 % fish oil. In conclusion, dietary fish oil prevented glomerular damage in MetS rats and mitigated the elevation in renal HETE levels. These results suggest a potential role for dietary fish oil to improve dysfunctional renal eicosanoid metabolism associated with kidney damage during conditions of the MetS.

Topics: 6-Ketoprostaglandin F1 alpha; Albuminuria; Animals; Dietary Fats; Dietary Supplements; Dinoprost; Disease Models, Animal; Fish Oils; Genotype; Hydroxyeicosatetraenoic Acids; Kidney Diseases; Kidney Glomerulus; Male; Metabolic Syndrome; Prostaglandin D2; Prostaglandins; Rats; Rats, Inbred Strains; Thromboxane B2

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

Obstructive sleep apnea (OSA) and metabolic syndrome (MetS) are associated with increased cardiovascular morbidity and mortality. Increased homocysteine is suggested as an independent risk factor for atherosclerosis and cardiovascular disease but remains disputed in OSA. We assessed polysomnography, carotid intima-media thickness (CIMT) and biology in 35 MetS patients, according to the presence (OSA+MetS; n=26) or the absence of OSA (MetS; n=9). In OSA+MetS patients, homocysteine levels were increased compared to MetS subjects (12.8 ± 3.8 vs. 9.5 ± 2.5 μmol/L; P=0.026). In the whole population, homocysteine correlated with apnea-hypopnea index (AHI) (r=0.522; P=0.001) and CIMT (r=0.376; P=0.026). Homocysteine was negatively correlated with plasma thiols (r=-0.406; P=0.017) and positively with urinary 15-F2t-isoprostanes (r=0.347; P=0.044). Multivariate regression analysis revealed that AHI (β=0.559; P<0.001) and urinary 15-F2t-isoprostane (β=0.310; P=0.018) were independently associated with homocysteine level. We conclude that homocysteine level was higher in MetS when associated with OSA and proportional to OSA severity. In this context, vascular remodeling appeared more severe and mediated by oxidative stress.

Topics: Antioxidants; Arousal; Atherosclerosis; Blood Pressure; Carotid Arteries; Carotid Intima-Media Thickness; Chromatography, High Pressure Liquid; Dinoprost; Endothelium, Vascular; Female; Homocysteine; Humans; Isoprostanes; Lipids; Male; Metabolic Syndrome; Middle Aged; Oxidation-Reduction; Oxidative Stress; Polysomnography; Sleep Apnea, Obstructive; Sulfhydryl Compounds; Tandem Mass Spectrometry

Newborn infants are at risk for oxidative stress leading to metabolic syndrome features. Oxidative stress can be induced by oxidant load such as oxygen supplementation, peroxides from intravenous nutrition, or low antioxidant defenses. We hypothesize that a modulation of antioxidant defenses during the neonatal period, without external oxidant challenge, will have a long-term influence on energy metabolism. Guinea pigs were fed between their third and their seventh day of life a regular chow leading to "mature" antioxidant defenses or a deficient chow leading to lower antioxidant defenses. Between weeks 1 and 14, the animals were fed regular chow. The hepatic oxidized redox status of glutathione associated with the deficient diet (-221 +/- 2 vs -228 +/- 1 mV, p < 0.01) was maintained until 14 weeks. At 13-14 weeks, animals fed the deficient diet presented lower plasma TG (479 +/- 57 vs 853 +/- 32 microM, p < 0.01), lower blood glucose (5.8 +/- 0.3 vs 6.9 +/- 0.3 mM, p < 0.05), and better tolerance to glucose (p < 0.05). Blood glucose correlated negatively with the redox status (r2 = 0.47, p < 0.01). Low antioxidant defenses during the neonatal period induce a better energy substrate profile associated with an oxidized redox status later in life. These findings suggest being aware of negative consequences when adopting "aggressive" antioxidant therapies in newborn infants.

Topics: Acetyl-CoA Carboxylase; Animals; Animals, Newborn; Antioxidants; Diet Therapy; Dinoprost; Food, Formulated; Gene Expression Regulation, Developmental; Glucose; Glucose Tolerance Test; Glutathione; Guinea Pigs; Hypoxia-Inducible Factor 1, alpha Subunit; Lipid Metabolism; Liver; Metabolic Syndrome; Oxidation-Reduction; Superoxide Dismutase; Time Factors; Triglycerides

Topics: Angiotensin II Type 1 Receptor Blockers; Cyclooxygenase 2 Inhibitors; Dinoprost; Humans; Intercellular Adhesion Molecule-1; Losartan; Metabolic Syndrome; PPAR gamma; Receptor, Angiotensin, Type 1; Thromboxane A2

This study was designed to examine the role of cyclooxygenase (COX) 2-mediated low-grade inflammation in the development of fructose-induced whole body and muscular insulin resistance in rats. The rats were on regular or fructose-enriched diets for 8 weeks. Fructose-fed rats were further divided into 3 groups (n = 8 per group). There were fructose-fed rats, fructose-fed rats with nimesulide (a selective COX2 inhibitor, 30 mg/kg/day, gavage) and fructose-fed rats with celecoxib (a selective COX2 inhibitor, 30 mg/kg/day, gavage). The present result showed that fructose-induced time-dependent increases in systolic blood pressure and fasting plasma insulin and triglyceride levels were significantly suppressed in rats treated with nimesulide or cerecoxib. The ratio of area under glucose curve divided by area under insulin curve obtained during the oral glucose tolerance test was significantly decreased in fructose-fed rats, which were markedly reversed in those co-treated with nimesulide or celecoxib. Accordingly, fructose-induced decrease in insulin-stimulated glucose uptake in soleus muscle was significantly reversed in those combined with nimesulide or celecoxib. Fructose-induced time-dependent increases in plasma 8-isoprostane and PGE metabolites were concomitantly suppressed by nimesulide or celecoxib co-treatment. The present study demonstrates that the COX2-mediated low-grade inflammation, especially mediated by increase in oxidative stress was important in the development of insulin resistance in fructose-fed rats.

Topics: Animals; Blood Pressure; Body Weight; Cyclooxygenase 2; Dinoprost; Disease Models, Animal; Fructose; Glucose; Glucose Tolerance Test; Hypoglycemic Agents; Inflammation; Insulin; Insulin Resistance; Male; Metabolic Syndrome; Muscle, Skeletal; Prostaglandins E; Rats; Rats, Sprague-Dawley; Sweetening Agents

The metabolic syndrome (MetS) is a major target for prevention of atherosclerotic cardiovascular diseases and visceral fat accumulation is an underlying component of MetS. The aim of this study was to investigate the association of systemic oxidative stress with visceral fat accumulation and MetS.. The study group consisted of Japanese men (n=44; 51.2+/-11.4 years) and women (n=61; 55.4 +/-13.4 years). Urinary 8-epi-prostaglandin F2alpha (8-epi-PGF2 alpha) concentration, a biomarker of systemic oxidative stress, was significantly high in the subjects with MetS. As the urinary concentration of 8-epi-PGF2alpha increased, the number of criteria for MetS were significantly met (abdominal obesity, hypertriglyceridemia, low high-density lipoprotein-cholesterol, hypertension, and high fasting glucose). Among parameters associated with MetS, the correlation coefficient of visceral fat area (VFA) with urinary 8-epi-PGF2alpha concentration was the highest (r=0.636, p<0.0001). In non-obese subjects, the correlation coefficient of VFA with urinary 8-epi-PGF2alpha concentration was higher (r=0.728, p<0.0001), although there was no significant correlation between subcutaneous fat area and urinary 8-epi-PGF2 alpha. Stepwise multiple regression analysis identified VFA as the strongest and independent determinant of urinary 8-epi-PGF2 alpha (p<0.0001) followed by adiponectin (p=0.0212) and, high sensitive C-reactive protein (p=0.0365).. Systemic oxidative stress, as measured by urinary 8-epi-PGF2alpha , is strongly associated with visceral fat accumulation and MetS.

Topics: Adiponectin; Adult; Aged; C-Reactive Protein; Cross-Sectional Studies; Dinoprost; Female; Humans; Intra-Abdominal Fat; Male; Metabolic Syndrome; Middle Aged; Oxidative Stress; Reactive Oxygen Species; Regression Analysis

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

The metabolic syndrome predisposes to the development of cardiovascular diseases. Oxidative stress and elevated circulating oxidized low-density lipoprotein (LDL) concentrations are related to cardiovascular disease and proposed to be features of the metabolic syndrome. F2-isoprostanes are lipid peroxidation products and considered the most reliable biomarkers of oxidative stress.. Plasma oxidized LDL (oxLDL) and urinary 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha; the major F2-isoprostane) were analyzed in a cross-sectional study of 289 healthy men (62 to 64 years of age). Individuals completed a 7-day dietary record, and fasting plasma insulin, lipid, and lipoprotein concentrations, LDL particle size, and inflammatory markers were determined. National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATPIII) criteria were used to define the metabolic syndrome and individuals were grouped according to the number of risk factors for the metabolic syndrome (0, [n=88; 30%]; > or =1, [n=179; 62%], metabolic syndrome [n=22; 8%]). Group comparisons revealed no differences for oxLDL, 8-iso-PGF2alpha, or reported intake of macronutrients, whereas C-reactive protein and interleukin-6 were increased in the metabolic syndrome. LDL cholesterol strongly determined oxLDL in univariate and multivariate analysis, but no relationship to 8-iso-PGF2alpha was found. In turn, 8-iso-PGF2alpha was related to reported intake of fat, fatty acids, and dietary antioxidants.. There were no increases in plasma oxLDL or measures of oxidative stress (urinary 8-iso-PGF2alpha) in these otherwise healthy 63-year-old men with the metabolic syndrome. Furthermore, no relationship between oxLDL and 8-iso-PGF2alpha was found, but our results suggest a role for dietary factors in oxidative stress.

Topics: Atherosclerosis; Dinoprost; Feeding Behavior; Humans; Lipoproteins, LDL; Male; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Nutrition Assessment; Oxidative Stress; Risk Factors