Determination of DNA damage induced by oxidative stress in hyperlipidemic patients

In the present paper, we report data on the genotoxic properties of hydrogen peroxide in polymorphonuclear neutrophils (PMNLs) separated from normolipidemic and type II/a hyperlipidemic patients. In all, 15 hyperlipidemic patients (11 female, 4 male, mean age 54.6±10.25 years) were involved in the study, and 7 normolipidemic patients (5 female, 2 male, mean age 53.4±8.07 years) served as controls. Using the comet assay, there was a significant difference in the degree of DNA damage between the two groups. The visual score characteristic of the degree of DNA damage was 350.97±31.31 in the hyperlipidemic group, while it was 289.5±29.49 in the control group (P<0.001). In the hyperlipidemic patients, a positive correlation was found between the degree of DNA damage and the basic oxidation of PMNLs (r=0.517), and the superoxide anion production of the cells stimulated with phorbolmiristate acetate (PMA) (r=0.326) and formyl-Met–Leu–Phe (FMLP) (r=0.525) as well. There was a negative correlation between DNA damage and HDL-associated antioxidant paraoxonase (PON) activity (r=−0.469), and the PON/HDL ratio (r=−0.631). No correlation was found between the degree of DNA damage and the plasma concentration of nitric oxide (NO) (r=0.098) and thiobarbituric acid-reactive substances (TBARS) (r=0.061) in hyperlipidemic patients. Our results show that in hyperlipidemic patients there is an increase in lymphocyte DNA damage caused by oxidative stress when compared to normolipidemic individuals as demonstrated by comet assay. Decreased antioxidant capacity in hyperlipidemic patients may play a significant role in this process.     

An SNP in the Adiponectin Gene Is Associated with Decreased Serum Adiponectin Levels and Risk for Impaired Glucose Tolerance

Adiponectin is a plasma protein produced by the adipose tissue. Hypoadiponectinemia has been associated with insulin resistance and several components of the metabolic syndrome (MS): type 2 diabetes, obesity, and dyslipidemia. We investigated whether single nucleotide polymorphisms (SNPs) at positions 45 and 276 in the adiponectin gene were associated with features of the MS in 747 unrelated Spanish subjects. The G allele of SNP45 and the G/G genotype of SNP276 were associated with impaired glucose tolerance (p = 0.020 and 0.042, respectively). The G/G genotype for SNP276 was associated with lower serum adiponectin levels as compared with the G/T and T/T genotypes (G/G, 10.10 ± 0.24 μg/mL; G/T, 10.98 ± 0.32 μg/mL; T/T, 12.00 ± 0.92 μg/mL; p = 0.015) even after adjustment for sex, age, BMI, waist‐to‐hip ratio, homeostasis model assessment index, and the degree of glucose tolerance (p = 0.040). We found a significant negative association of circulating adiponectin levels with waist‐to‐hip ratio (r = ?0.42, p < 0.001), sagittal abdominal diameter (r = ?0.24, p < 0.001), triglycerides (r = ?0.32, p < 0.001), homeostasis model assessment index (r = ?0.14, p = 0.001), and uric acid (r = ?0.36, p < 0.001) and positive association with high‐density lipoprotein‐cholesterol (r = 0.41, p < 0.001). Our findings indicate that serum adiponectin levels are associated with several components of the MS. The SNP276 of the adiponectin gene may affect impaired glucose tolerance and hypoadiponectinemia.     

Decreased paraoxonase 2 enzymatic activity in monocyte/macrophages cells. A comparative in vivo and in vitro study for diabetes

Aim: To investigate peripheral blood monocytes/macrophages (Mo/M?) paraoxonase 2 (PON2) in diabetes and the factors modulating its activity.

Methods: One hundred and eighteen patients with newly diagnosed uncomplicated type 2 diabetes mellitus were compared regarding clinical, biochemical and oxidative stress parameters with 80 healthy subjects. The capacity of the peripheral blood mononuclear cells (PBMNC) to release pro-oxidants and to neutralise them was determined by measuring the respiratory burst (RB) and the intracellular antioxidant enzyme PON2. In vitro experiments were conducted on a differentiated monocytes cell line (dU937) that was exposed to serum deprivation followed by addition of isolated lipoproteins (VLDL or LDL).

Results: Paraoxonase 2 activity in Mo/M? was significantly lower in type 2 diabetes patients (0.042?±?0.044 vs 0.165?±?0.133U lactonase activity/mg protein in controls, p?1c) and insulin resistance (HOMA-IR). In multivariate regression models, 15–34% of the PON2 variance was explained by diabetes. The in vitro addition of VLDL normalised the RB of serum deprived dU937 cells, S? (to 82?±?18% of the cells incubated with serum, S+) and PON2 activity (from 0.524?±?0.061 in S???to 0.298?±?0.048?U/mg protein). In contrast, when LDL was added, the RB remained lower (61?±?12% of S+, p?=?.03) and PON2 higher (0.580?±?0.030?U/mg protein, p?=?.003).

Conclusions: The decrease in monocyte/macrophage PON2 enzymatic activity observed in type 2 diabetes cannot be totally explained by abdominal obesity and insulin resistance. The underlying molecular mechanisms need to be identified.     

Plasma Adiponectin Levels in High Risk African‐Americans with Normal Glucose Tolerance,Impaired Glucose Tolerance,and Type 2 Diabetes**

Objective: We studied plasma adiponectin, insulin sensitivity, and insulin secretion before and after oral glucose challenge in normal glucose tolerant, impaired glucose tolerant, and type 2 diabetic first degree relatives of African‐American patients with type 2 diabetes. Research Methods and Procedures: We studied 19 subjects with normal glucose tolerance (NGT), 8 with impaired glucose tolerance (IGT), and 14 with type 2 diabetes. Serum glucose, insulin, C‐peptide, and plasma adiponectin levels were measured before and 2 hours after oral glucose tolerance test. Homeostasis model assessment‐insulin resistance index (HOMA‐IR) and HOMA‐β cell function were calculated in each subject using HOMA. We empirically defined insulin sensitivity as HOMA‐IR < 2.68 and insulin resistance as HOMA‐IR > 2.68. Results: Subjects with IGT and type 2 diabetes were more insulin resistant (as assessed by HOMA‐IR) when compared with NGT subjects. Mean plasma fasting adiponectin levels were significantly lower in the type 2 diabetes group when compared with NGT and IGT groups. Plasma adiponectin levels were 2‐fold greater (11.09 ± 4.98 vs. 6.42 ± 3.3811 μg/mL) in insulin‐sensitive (HOMA‐IR, 1.74 ± 0.65) than in insulin‐resistant (HOMA‐IR, 5.12 ± 2.14) NGT subjects. Mean plasma adiponectin levels were significantly lower in the glucose tolerant, insulin‐resistant subjects than in the insulin sensitive NGT subjects and were comparable with those of the patients with newly diagnosed type 2 diabetes. We found significant inverse relationships of adiponectin with HOMA‐IR (r = ?0.502, p = 0.046) and with HOMA‐β cell function (r = ?0.498, p = 0.042) but not with the percentage body fat (r = ?0.368, p = 0.063), serum glucose, BMI, age, and glycosylated hemoglobin A1C (%A1C). Discussion: In summary, we found that plasma adiponectin levels were significantly lower in insulin‐resistant, non‐diabetic first degree relatives of African‐American patients with type 2 diabetes and in those with newly diagnosed type 2 diabetes. We conclude that a decreased plasma adiponectin and insulin resistance coexist in a genetically prone subset of first degree African‐American relatives before development of IGT and type 2 diabetes.     

Loss of Total and Visceral Adipose Tissue Mass Predicts Decreases in Oxidative Stress After Weight‐loss Surgery

It is not known whether there are mechanisms linking adipose tissue mass and increased oxidative stress in obesity. This study investigated associations between decreasing general and abdominal fat depots and oxidative stress during weight loss. Subjects were severely obese women who were measured serially at baseline and at 1, 6 (n = 30), and 24 months (n = 18) after bariatric surgery. Total fat mass (FAT) and volumes of visceral (VAT) and subcutaneous abdominal adipose tissue (SAT) were related to plasma concentrations of derivatives of reactive oxidative metabolites (dROMS), a measure of lipid peroxides and oxidative stress. After intervention, BMI significantly decreased, from 47.7 ± 0.8 kg/m² to 43.3 ± 0.8 kg/m² (1 month), 35.2 ± 0.8 kg/m² (6 months), and 30.2 ± 1.2 kg/m² (24 months). Plasma dROMS also significantly deceased over time. At baseline, VAT (r = 0.46), FAT (r = 0.42), and BMI (r = 0.37) correlated with 6‐month decreases in dROMS. Similarly, at 1 month, VAT (r = 0.43) and FAT (r = 0.41) correlated with 6‐month decreases in dROMS. Multiple regression analysis showed that relationships between VAT and dROMS were significant after adjusting for FAT mass. Increased plasma dROMS at baseline were correlated with decreased concentrations of high‐density lipoprotein (HDL) at 1 and 6 months after surgery (r = ?0.38 and ?0.42). This study found longitudinal associations between general, and more specifically intra‐abdominal adiposity, and systemic lipid peroxides, suggesting that adipose tissue mass contributes to oxidative stress.     

Paraoxonase 1 gene polymorphisms, paraoxonase/arylesterase activities and oxidized low-density lipoprotein levels in patients with migraine

The vascular endothelial dysfunction has been implicated in the pathogenesis of migraine. Oxidized low‐density lipoprotein (ox‐LDL) may impair endothelial function. Paraoxonase‐1 (PON‐1) prevents oxidative modification of LDL cholesterol (LDL‐C). So we investigated serum PON‐1 and arylesterase (ARE) activities, PON‐1 55 L/M and 192Q/R polymorphisms and the serum lipid profile in patients with migraine. Biochemical parameters and PON‐1 polymorphism analyses were assessed in 104 patients with migraine and 86 healthy subjects. Ox‐LDL was detected by ELISA, and polymorphisms were determined using PCR–restriction fragment length polymorphism analysis. Patients with migraine had lower PON‐1 and ARE activities (p < 0·001, for both) and higher ox‐LDL and LDL‐C levels (p < 0·001, for both) and ox‐LDL: LDL‐C ratio (p < 0·005) than the controls. The genotype distribution and the allele frequencies for PON‐1 55 L/M and 192Q/R polymorphisms were not different among the study populations. The results of our current study indicate that migrainous patients have decreased serum PON‐1 and ARE activities and increased serum ox‐LDL levels, which may have a clinical importance in the treatment of migraine. Copyright © 2011 John Wiley & Sons, Ltd.     

Early decreases in plasma lipid transfer proteins during weight reduction

Objective: To determine the effect of short‐term weight loss in obese women on concentrations of plasma cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP), two new risk factors for cardiovascular disease. Research Methods and Procedures: Plasma CETP and PLTP mass concentrations were measured in 38 obese, non‐diabetic women before and after a moderate, 4% weight loss that was obtained by a 1250 kcal/d diet for 4 weeks. Anthropometric and biological parameters were measured before and after weight loss. Results: Plasma CETP concentration decreased substantially after weight loss (2.76 ± 0.79 before and 2.31 ± 0.69 mg/L after; p = 0.000), and the same was true for plasma PLTP concentration (9.01 ± 2.44 mg/L before vs. 8.34 ± 2.57 after; p = 0.043). The HDL profile shifted toward the small‐sized range, with significant decreases in the relative abundance of HDL_2b and HDL_2a at the expense of HDL_3b after weight loss. A significant, positive correlation between CETP and PLTP mass concentrations is reported for the first time in obese patients (r = 0.43, p = 0.004), and weight reduction was accompanied by early, concomitant, and parallel decreases in plasma CETP and PLTP levels (r = 0.47, p = 0.003). The significant relationship between CETP and PLTP levels was lost after the dietary intervention (r = 0.27; p = 0.11). Discussion: CETP and PLTP correlate positively and significantly in obese patients. The hypocaloric dietary manipulation constitutes a relevant intervention to reduce rapidly and simultaneously plasma levels of CETP and PLTP. The impact of reduced PLTP activity on HDL size appeared to be more prominent than the impact of concomitant reduction in CETP activity.     

Elevated serum monocyte chemoattractant protein-4 and chronic inflammation in overweight subjects

Objective: Chronic inflammation observed in obesity has been reported to be implicated in the development of atherosclerosis. We screened candidate chemokines that link chronic inflammation and obesity. Research Methods and Procedures: Japanese overweight (n = 39, BMI 28.7 ± 0.65 kg/m²) and normal‐weight (n = 24, BMI 22.3 ± 0.45 kg/m²) subjects were enrolled. Using antibody‐based protein microarray, spot intensities of monocyte chemoattractant protein (MCP)‐4, eotaxin, and eotaxin‐2 correlated with anthropometric parameters. We further measured serum concentration of these chemokines and mRNA levels in adipose tissues obtained from volunteers. Results: Serum MCP‐4 levels showed positive correlation with BMI (r = 0.318, p = 0.014), waist (r = 0.316, p = 0.018), and waist‐to‐hip ratio (WHR) (r = 0.264, p = 0.049). Furthermore, MCP‐4 correlated with homeostasis model assessment of insulin resistance (r = 0.392, p = 0.002), high‐sensitivity C‐reactive protein (hsCRP) (r = 0.350, p = 0.006). In step‐wise multiple regression analyses, hsCRP independently correlated with MCP‐4 levels. The expression of MCP‐4 mRNA in visceral adipose tissue positively correlates with BMI. Serum eotaxin levels correlate with BMI (r = 0.262, p = 0.045) and WHR (r = 0.383, p = 0.003). Serum eotaxin‐2 levels correlated with BMI (r = 0.464, p < 0.001), waist (r = 0.333, p = 0.017), and WHR (r = 0.278, p = 0.048). However, eotaxin and eotaxin‐2 levels did not show significant correlation with hsCRP. Discussion: Serum levels of MCP‐4, eotaxin, and eotaxin‐2, which belong to CC chemokine family and share CC chemokine receptor 3, correlated with BMI. These chemokines, especially MCP‐4, may be critical molecules that link obesity and chronic inflammation.     

Assessment of DNA damage in sperm after repeated non‐invasive sampling in zebrafish Danio rerio

Repeated non‐invasive sampling of zebrafish Danio rerio sperm was conducted, sperm counts were obtained and a method for measurement of DNA damage in sperm was developed and validated (single‐cell gel electrophoresis, comet, assay). DNA damage in sperm increased with concentration of hydrogen peroxide (H₂O₂, 0–200 µM), and in vitro exposure of sperm to 200 µM H₂O₂ produced 88·7 ± 3·9% tail DNA compared to unexposed controls [12 ± 0·7% tail DNA (mean ± s.e ., n = 3)]. Frequency of sperm sampling (sampled every 2, 4 or 7 days) did not affect DNA damage in sperm, but sperm counts decreased 57 and 22% for fish sampled every 2 or 4 days, respectively.     

Physical activity-related energy expenditure with the RT3 and TriTrac accelerometers in overweight adults

Objective: The objective was to evaluate two accelerometers, the RT3 and the TriTrac‐R3D for their ability to produce estimates of physical activity‐related energy expenditure (PAEE) in overweight/obese adults. Research Methods and Procedures: PAEE estimates from both accelerometers were obtained in two experiments. In Experiment 1, 13 overweight/obese subjects (BMI 34.2 ± 6.4 kg/m²) were monitored over 2 weeks in everyday life, PAEE being simultaneously measured by the doubly labeled water method (DLW). In Experiment 2, 8 overweight/obese subjects (BMI 34.3 ± 5.0 kg/m²) and 10 normal‐weight subjects (BMI 20.8 ± 2.1 kg/m²) were monitored during a treadmill walking protocol, PAEE being simultaneously measured by indirect calorimetry. Results: In Experiment 1, there was no significant difference between methods in mean PAEE (DLW: 704 ± 223 kcal/d, RT3: 656 ± 140 kcal/d, TriTrac‐R3D 624 ± 419 kcal/d). The relative difference between methods (accelerometer vs. DLW) was ?17.1% ± 16.7% for the RT3 and ?20.0 ± 44.6% for the TriTrac‐R3D. Correlation for PAEE between RT3 and DLW was higher than between TriTrac‐R3D and DLW (r = 0.67, p < 0.05 and r = 0.36, p = 0.25, respectively). The 95% confidence interval (CI) (kcal/d) of the mean difference between methods was large, amounting to ?385 to 145 for the RT3 and ?887 to 590 for the TriTrac‐R3D. In Experiment 2, both accelerometers were sensitive to the changes in treadmill speed, with no significant difference in mean PAEE between methods in overweight/obese subjects. Conclusions: Although both accelerometers did not provide accurate estimates of PAEE at individual levels, the data suggest that RT3 has the potential to assess PAEE at group levels in overweight/obese subjects.     

Triglyceride‐to‐HDL‐cholesterol Ratio and Metabolic Syndrome as Contributors to Cardiovascular Risk in Overweight Patients

Insulin resistance increases cardiovascular risk of obese patients. Triglyceride to high‐density lipoprotein cholesterol ratio (TG/HDL) ≥3.0 (in mg/dl) is a marker of insulin resistance in overweight persons. We aimed at assessing cardiovascular risk profile in 301 overweight elderly Neapolitan outpatients, according to TG/HDL ratio and metabolic syndrome (MS), diagnosed by National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. TG/HDL ratio was ≥3.0 in 97 patients (group A) and <3.0 in 204 (group B). Overall, 93–97% of group A patients and 38–51% of group B patients had MS, depending on the diagnostic criterion. Group A patients with MS had significantly higher waist‐to‐hip ratio, total and non‐HDL cholesterol than group B patients with MS. In group B, MS and non‐MS patients had similar waist‐to‐hip ratio, blood pressure, total and non‐HDL cholesterol. Ten year coronary risk, calculated by the Framingham equations (n = 243), was 10.3 ± 5% in group B, non‐MS patients; 13.1 ± 6% in group B, MS patients; 19.9 ± 8% in group A (F = 32.8; P < 0.001). At the multiple regression analysis, TG/HDL ratio was associated with coronary risk (r² = 0.227) more closely than gender, blood pressure, waist‐to‐hip ratio, non HDL cholesterol, and MS considered as a whole. A separate regression analysis showed that the logarithmically transformed TG/HDL ratio, an index of the HDL cholesterol esterification rate, is also associated with coronary risk (r² = 0.252). Thus, TG/HDL ratio could help to characterize high‐risk overweight patients deserving a special therapeutic effort. Cardiovascular risk profile of insulin‐sensitive patients, identified by lower values of this parameter, is only moderately affected by MS.     

Leptin Responses to Weight Loss in Postmenopausal Women: Relationship to Sex‐Hormone Binding Globulin and Visceral Obesity

Objective: Leptin concentrations increase with obesity and tend to decrease with weight loss. However, there is large variation in the response of serum leptin levels to decreases in body weight. This study examines which endocrine and body composition factors are related to changes in leptin concentrations following weight loss in obese, postmenopausal women. Research Methods and Procedures: Body composition (DXA), visceral obesity (computed tomography), leptin, cortisol, insulin, and sex hormone‐binding globulin (SHBG) concentrations were measured in 54 obese (body mass index [BMI] = 32.0 ± 4.5 kg/m²; mean ± SD), women (60 ± 6 years) before and after a 6‐month hypocaloric diet (250 to 350 kcal/day deficit). Results: Body weight decreased by 5.8 ± 3.4 kg (7.1%) and leptin levels decreased by 6.6 ± 11.9 ng/mL (14.5%) after the 6‐month treatment. Insulin levels decreased 10% (p < 0.05), but mean SHBG and cortisol levels did not change significantly. Relative changes in leptin with weight loss correlated positively with relative changes in body weight (r = 0.50, p < 0.0001), fat mass (r = 0.38, p < 0.01), subcutaneous fat area (r = 0.52, p < 0.0001), and with baseline values of SHBG (r = 0.38, p < 0.01) and baseline intra‐abdominal fat area (r = ?0.27, p < 0.06). Stepwise multiple regression analysis showed that baseline SHBG levels (r² = 0.24, p < 0.01), relative changes in body weight (cumulative r² = 0.40, p < 0.05), and baseline intra‐abdominal fat area (cumulative r² = 0.48, p < 0.05) were the only independent predictors of the relative change in leptin, accounting for 48% of the variance. Discussion: These results suggest that obese, postmenopausal women with a lower initial SHBG and more visceral obesity have a greater decrease in leptin with weight loss, independent of the amount of weight lost.     

True fractional calcium absorption is decreased after Roux-en-Y gastric bypass surgery

Objective: Roux‐en‐Y gastric bypass (RYGB) is considered to be the gold standard alternative treatment for severe obesity. Weight loss after RYGB results primarily from decreased food intake. Inadequate calcium (Ca) intake and metabolic bone disease can occur after gastric bypass. To our knowledge, whether malabsorption of Ca contributes to an altered Ca metabolism in the RYGB patient has not been addressed previously. Research Methods and Procedures: We recruited 25 extremely obese women in order to study true fractional Ca absorption (TFCA) before and 6 months after RYGB surgery, using a dual stable isotope method (⁴²Ca and ⁴³Ca) and test load of Ca (200 mg). Hormones regulating Ca absorption and markers of bone turnover were also measured. Results: In 21 women (BMI 52.7 ± 8.3 kg/m², age 43.9 ± 10.4 years) who successfully completed the study, TFCA decreased from 0.36 ± 0.08 to 0.24 ± 0.09 (p < 0.001) after RYGB. Bone turnover markers increased significantly (p < 0.01). TFCA correlated with estradiol levels (r = 0.512, p < 0.02) and tended to correlate with 1,25 (OH)₂D (r = 0.427, p < 0.06) at final measurement. Stepwise linear regression indicated that estradiol explained 62% of the variance for TFCA at 6 months post‐surgery (p < 0.01). Discussion: TFCA decreases (0.12 ± 0.08) after RYGB surgery but remains within normal range. Although only some patients were estimated to have low Ca absorption after surgery, all of the patients showed a dramatic increase in markers of bone resorption. The alteration in Ca metabolism after RYGB‐induced weight loss appears to be regulated primarily by estradiol levels and might ultimately affect bone mass.     

Retinol‐binding Protein 4 (RBP4) Protein Expression Is Increased in Omental Adipose Tissue of Severely Obese Patients

Visceral fat has been linked to insulin resistance and type 2 diabetes mellitus (T2DM); and emerging data links RBP4 gene expression in adipose tissue with insulin resistance. In this study, we examined RBP4 protein expression in omental adipose tissue obtained from 24 severely obese patients undergoing bariatric surgery, and 10 lean controls (4 males/6 females, BMI = 23.2 ± 1.5 kg/m²) undergoing elective abdominal surgeries. Twelve of the obese patients had T2DM (2 males/10 females, BMI: 44.7 ± 1.5 kg/m²) and 12 had normal glucose tolerance (NGT: 4 males/8 females, BMI: 47.6 ± 1.9 kg/m²). Adipose RBP4, glucose transport protein‐4 (GLUT4), and p85 protein expression were determined by western blot. Blood samples from the bariatric patients were analyzed for serum RBP4, total cholesterol, triglycerides, and glucose. Adipose RBP4 protein expression (NGT: 11.0 ± 0.6; T2DM: 11.8 ± 0.7; lean: 8.7 ± 0.8 arbitrary units) was significantly increased in both NGT (P = 0.03) and T2DM (P = 0.005), compared to lean controls. GLUT4 protein was decreased in both NGT (P = 0.02) and T2DM (P = 0.03), and p85 expression was increased in T2DM subjects, compared to NGT (P = 0.03) and lean controls (P = 0.003). Regression analysis showed a strong correlation between adipose RBP4 protein and BMI for all subjects, as well as between adipose RBP4 and fasting glucose levels in T2DM subjects (r = 0.76, P = 0.004). Further, in T2DM, serum RBP4 was correlated with p85 expression (r = 0.68, P = 0.01), and adipose RBP4 protein trended toward an association with p85 protein (r = 0.55, P = 0.06). These data suggest that RBP4 may regulate adiposity, and p85 expression in obese‐T2DM, thus providing a link to impaired insulin signaling and diabetes in severely obese patients.     

Specific prediction of mortality by oxidative stress-induced damage to RNA vs. DNA in humans

Modifications of nucleic acids (DNA and RNA) from oxidative stress is a potential driver of aging per se and of mortality in age-associated medical disorders such as type 2 diabetes (T2D). In a human cohort, we found a strong prediction of all-cause mortality by a marker of systemic oxidation of RNA in patients with T2D (n = 2672) and in nondiabetic control subjects (n = 4079). The finding persisted after the adjustment of established modifiers of oxidative stress (including BMI, smoking, and glycated hemoglobin). In contrast, systemic levels of DNA damage from oxidation, which traditionally has been causally linked to both T2D and aging, failed to predict mortality. Strikingly, these findings were subsequently replicated in an independent general population study (n = 3649). The data demonstrate a specific importance of RNA damage from oxidation in T2D and general aging.     

Epicardial adipose tissue assessed by cardiac magnetic resonance imaging in patients with heart failure due to dilated cardiomyopathy

Objective:

We sought to investigate the association of the EAT with CMR parameters of ventricular remodelling and left ventricular (LV) dysfunction in patients with non‐ischemic dilated cardiomyopathy (DCM).

Design and Methods:

One hundred and fifty subjects (112 consecutive patients with DCM and 48 healthy controls) underwent CMR examination. Function, volumes, dimensions, the LV remodelling index (LVRI), the presence of late gadolinium enhancement (LGE) and the amount of EAT were assessed.

Results:

Compared to healthy controls, patients with DCM revealed a significantly reduced indexed EAT mass (31.7 ± 5.6 g/m² vs 24.0 ± 7.5 g/m², p<0.0001). There was no difference in the EAT mass between DCM patients with moderate and severe LV dysfunction (23.5 ± 9.8 g/m² vs 24.2 ± 6.6 g/m², P = 0.7). Linear regression analysis in DCM patients showed that with increasing LV end‐diastolic mass index (LV‐EDMI) (r = 0.417, P < 0.0001), increasing LV end‐diastolic volume index (r = 0.251, P = 0.01) and increasing LV end‐diastolic diameter (r = 0.220, P = 0.02), there was also a significantly increased amount of EAT mass. However, there was no correlation between the EAT and the LV ejection fraction (r = 0.0085, P = 0.37), right ventricular ejection fraction (r = 0.049, P = 0.6), LVRI (r = 0.116, P = 0.2) and the extent of LGE % (r = 0.189, P = 0.1). Among the healthy controls, the amount of EAT only correlated with increasing age (r = 0.461, P = 0.001), BMI (r = 0.426, P = 0.003) and LV‐EDMI (r = 0.346, P = 0.02).

Conclusion:

In patients with DCM the amount of EAT is decreased compared to healthy controls irrespective of LV function impairment. However, an increase in LV mass and volumes is associated with a significantly increase in EAT in patients with DCM.     

Epigenetic patterns of two gene promoters (TNF-α and PON) in stroke considering obesity condition and dietary intake

Some causal bases of stroke remain unclear, but the nutritional effects on the epigenetic regulation of different genes may be involved. The aim was to assess the impact of epigenetic processes of human tumor necrosis factor (TNF-α) and paraoxonase (PON) promoters in the susceptibility to stroke when considering body composition and dietary intake. Twenty-four patients (12 non-stroke/12 stroke) were matched by sex (12 male/12 female), age (mean 70?±?12 years old), and BMI (12 normal-weight/12 obese; mean 28.1?±?6.7 kg/m²). Blood cell DNA was isolated and DNA methylation levels of TNF-α (?186 to +349 bp) and PON (?231 to +250 bp) promoters were analyzed by the Sequenom EpiTYPER approach. Histone modifications (H3K9ac and H3K4me3) were analyzed also by chromatin immunoprecipitation in a region of TNF-α (?297 to ?185). Total TNF-α promoter methylation was lower in stroke patients (p?<?0.001) and showed no interaction with body composition (p?=?0.807). TNF-α and PON total methylation levels correlated each other (r?=?0.44; p?=?0.031), especially in stroke patients (r?=?0.72; p?=?0.008). The +309 CpG methylation site from TNF-α promoter was related to body weight (p?=?0.027) and the region containing three CpGs (from ?170 to ?162 bp) to the percentage of lipid intake and dietary indexes (p?<?0.05) in non-stroke patients. The methylation of PON +15 and +241 CpGs was related to body weight (p?=?0.021), waist circumference (p?=?0.020), and energy intake (p?=?0.018), whereas +214 was associated to the quality of the diet (p?<?0.05) in non-stroke patients. When comparing stroke vs non-stroke patients regarding the histone modifications analyzed at TNF-α promoter, no changes were found, although a significant association was identified between circulating TNF-α level and H3K9ac with H3K4me3. TNF-α and PON promoter methylation levels could be involved in the susceptibility to stroke and obesity outcome, respectively. The dietary intake and body composition may influence this epigenetic regulation in non-stroke patients.     

The effects of Goami No. 2 rice, a natural fiber-rich rice, on body weight and lipid metabolism

Objective : Increased intake of dietary fiber reduces the risk of obesity and type 2 diabetes. We assessed the effects of a fiber‐rich diet on body weight, adipokine concentrations, and the metabolism of glucose and lipids in non‐obese and obese subjects in Korea, where rice is the main source of dietary carbohydrates. Research Methods and Procedures : Eleven healthy, non‐obese and 10 obese subjects completed two 4‐week phases of individual isoenergetic food intake. During the control diet phase, subjects consumed standard rice; during the modified diet phase, subjects consumed equal proportions of fiber‐rich Goami No. 2 rice and standard rice. We used a randomized, controlled, crossover study design with a washout period of 6 weeks between the two phases. Results : After the modified diet phase, body weight was significantly lower in both the non‐obese and obese subjects (non‐obese, 57.0 ± 2.9 vs. 56.1 ± 2.8 kg, p = 0.001; obese, 67.7 ± 2.1 vs. 65.7 ± 2.0 kg, p < 0.001 for before vs. after). The BMI was significantly lower in obese subjects (26.9 ± 0.5 vs. 26.0 ± 0.6 kg/m², p < 0.001). The modified diet was associated with lower serum triacylglycerol (p < 0.01), total cholesterol (p < 0.01), low‐density lipoprotein cholesterol (p < 0.05), and C‐peptide (p < 0.05) concentrations in the obese subjects. Discussion : These results indicate that fiber‐rich Goami No. 2 rice has beneficial effects and may be therapeutically useful for obese subjects.     

Weight Loss Reduces Tissue Factor in Morbidly Obese Patients

Objective: To investigate the tissue factor (TF) pathway in clinical obesity and associated metabolic syndrome. Research Methods and Procedures: Thirty‐seven morbidly obese patients (4 men; BMI, 48 ± 7 kg/m²; range, 42 to 53 kg/m²), undergoing elective gastroplasty for the induction of weight loss, were examined for hemostatic, metabolic, and inflammatory parameters at baseline and 14 ± 5 months postoperatively. Results: Weight loss significantly reduced circulating plasma TF (314 ± 181 vs. 235 ± 113 pg/mL, p = 0.04), coagulation factor VII (130 ± 22% vs. 113 ± 19%, p = 0.023), and prothrombin fragment F1.2 (2.4 ± 3.4 vs. 1.14 ± 1.1 nM, p = 0.04) and normalized glucose metabolism in 50% of obese patients preoperatively classified as diabetic or of impaired glucose tolerance. The postoperative decrease in plasma TF correlated with the decrease of F1.2 (r = 0.56; p = 0.005), a marker of in vivo thrombin formation. In subgroup analysis stratified by preoperative glucose tolerance, baseline circulating TF (402.6 ± 141.6 vs. 176.2 ± 58.2, p < 0.001) and TF decrease after gastroplasty (ΔTF: 164.7 ± 51.4 vs. ?81 ± 31 pg/mL, p = 0.02) were significantly higher in obese patients with impaired glucose tolerance than in patients with normal glucose tolerance. Discussion: Procoagulant TF is significantly reduced with weight loss and may contribute to a reduction in cardiovascular risk associated with obesity.