Adipokines,asymmetrical dimethylarginine,and pulmonary function in adolescents with asthma and obesity

Objective: This study was to investigate whether the metabolic abnormalities of adipokines and asymmetrical dimethylarginine (ADMA) associate with pulmonary function deficits in adolescents with obesity and asthma. Methods: This study enrolled 28 obese adolescents with asthma, 46 obese adolescents without asthma, 58 normal-weight adolescents with asthma, and 63 healthy control subjects. Serum levels of leptin, high-molecule-weight (HMW) adiponectin, retinol binding protein 4 (RBP4), asymmetrical dimethylarginine (ADMA), and pulmonary function were qualified. Results: The obese subjects had higher levels of leptin and ADMA but lower levels of HMW adiponectin than the normal-weight subjects with or without asthma. The subjects with asthma had higher levels of RBP4 than those without asthma. The obese adolescents with asthma had lowest forced expiratory lung volume in the first second (FEV₁)/forced vital capacity (FVC) ratio among the four study groups. In all the study subjects and in the subjects with asthma alone, the FEV₁/FVC ratio associated negatively with leptin, however, such association was rendered non-significant when adjusted for BMI. The pulmonary function deficits associated inversely with BMI percentile in the subjects with asthma. However, the decreased FEV₁/FVC ratio was not correlated with HMW adiponectin, RBP4 or ADMA. Conclusions: Our present study confirmed obstructive pattern of pulmonary function characterized by the reduced FEV₁/FVC ratio in the obese adolescents with asthma. These pulmonary deficits were associated inversely with the increased BMI percentile.     

超重及肥胖人群血清网膜素-1水平的变化

目的 探讨在南京地区人群中超重及肥胖者血清网膜素-1水平的变化及其与体重指数、腰围、脂联素之间的相关性.方法 从2008年3月至7月全国糖尿病和代谢综合征患病率及变迁调查江苏分中心的南京地区调查人群中,选取42例超重及肥胖者和55名健康对照者,分别测定体重指数、腰围、空腹胰岛素、窄腹血糖、血脂、血清网膜素-1及脂联素的水平,计算腰臀比及胰岛素抵抗指数.采用SPSS 15.0软件进行统计学分析,血清网膜素-1和各指标问的相关性分析采用Pearson相关分析法.结果 健康对照者的血清网膜素-1浓度为(0.024±0.012)μg/L,脂联素浓度为(7.7±2.4)mg/L,超重及肥胖者的血清网膜素-1浓度为(0.016±0.007)μg/L,脂联素浓度为(6.4±3.1)mg/L.结果 显示超重及肥胖者的血清网膜素-1及脂联素水平明显低于健康对照者(P<0.05),且相关分析表明血清网膜素-1与体重指数(r=-0.321,P<0.05)、腰围(r=-0.312,P<0.05)、腰臀比(r=0.243,P<0.05)及甘油三脂(r=-0.220,P<0.05)之间旱显著负相关,与脂联索(r=0.232,P<0.05)呈明显正相关.结论 超莆及肥胖者的血清网膜素-1水平较健康对照者显著下降,且血清网膜素-1浓度变化与脂联素之间呈正相关,提示网膜素水平变化可能与肥胖、胰岛素抵抗和2型糖尿病密切相关.     

Unchanged asymmetric dimethylarginine levels in non-diabetic, premenopausal obese women who have common risk factors for cardiovascular disease

This study was performed to test whether plasma asymmetric dimethylarginine (ADMA) concentrations are related to obesity and obesity complications including decrement in insulin sensitivity and adiponectin levels, dyslipidemia and low-grade inflammation. Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) concentrations were analyzed by HPLC in 17 overweight (BMI ≥ 25 kg/m²) and 40 obese (BMI ≥ 30 kg/m²) premenopausal women. Age-matched healthy women were studied as controls. Obesity did not give rise to a significant change in circulating ADMA levels but reduced in SDMA levels. As compared with control subjects (0.441 ± 0.102 μM), ADMA values in overweight and obese subjects were found to be as 0.412 ± 0.102 and 0.436 ± 0.093, respectively. No Pearson’s association of ADMA with relevant risk variables for cardiovascular disease, including blood pressure, insulin sensitivity, inflammatory markers, lipid and adiponectin levels. However, in linear regression analysis, BMI, diastolic blood pressure, glucose, insulin, and IL-8 emerged as significant predictors of ADMA. In spite of obese women have elevated hs-CRP, triglyceride levels and decreased insulin sensitivity, adiponectin and HDL-cholesterol levels, all of which is closely linked risk factors for cardiovascular disease, circulating ADMA levels remained unchanged in obese individuals as compared with controls.     

Relationship between obesity, smoking, and the endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine

We investigated the levels of asymmetric dimethylarginine (ADMA), an important endogenous inhibitor of nitric oxide (NO), as related to metabolic risk factors known to contribute to atherosclerotic disease. Dimethylarginines were analysed in a cross-sectional study of 563 elderly high-risk men (70 +/- 6 years). ADMA and the l-arginine/ADMA (l-arg/ADMA) ratio were highly significantly correlated with several metabolic risk factors. However, only the association with body mass index (BMI) remained significant after adjustment for inter-related variables. When analyzing the results according to being overweight or not, ADMA levels were independently significantly higher (P = .05) and the L-arg/ADMA ratios were significantly lower (P < .008) in individuals with high BMI (> or =26 kg/m(2), median value) as compared with subjects with low BMI. ADMA levels were furthermore significantly lower (P = .037) and L-arginine and the l-arg/ADMA ratios were significantly higher (P = .004 and P = .001, respectively) in smokers compared with nonsmokers, the latter being independent of other risk factors. The strong relationship found between BMI and plasma levels of ADMA and the l-arg/ADMA ratio indicate a link to endothelial dysfunction in overweight subjects. The beneficial dimethylarginine profile observed in smokers in this elderly population is not easily explainable and should be further investigated.     

Circulating nerve growth factor levels in relation to obesity and the metabolic syndrome in women

OBJECTIVE: Neurotrophins (NTs) could be involved in the development and progression of inflammatory and immune diseases. Because obesity and the metabolic syndrome (MetSyn) are related to a low-grade systemic inflammation, plasma NT levels (neurotrophinemia) could play an important role in the ethiopathogenic mechanisms underlying these metabolic derangements. This is the first study evaluating the plasma NT levels in a group of women with obesity and MetSyn, and also the adipose tissue nerve growth factor (NGF) expression in a small group of them. METHODS: Included were 146 adult women with different degrees of adiposity, with or without MetSyn. Plasma NT levels were measured. NGF expression was analyzed in s.c. adipose tissue of a subgroup of morbidly obese and normal-weight females. RESULTS: NGF plasma levels were 1.4-fold higher in overweight and obese subjects. Plasma NGF was, however, lower in a group of morbidly obese subjects than in overweight or obesity, but it remained elevated relative to the normal-weight group. Plasma NGF was significantly correlated with body mass index (BMI), percentage body fat, and waist circumference in non-morbidly obese subjects. NGF was positively related to inflammatory markers. NT3 and brain-derived neurotrophin factor seem to be more related to lipid profile than to BMI, adipose tissue distribution, or peripheral inflammatory markers. Subjects with type 2 diabetes, abdominal fat distribution, or the MetSyn showed significantly higher levels of NGF. The MetSyn was the only independent predictor of the variability observed in the NGF plasma values. CONCLUSION: NGF is upregulated in obesity, type 2 diabetes, and the MetSyn. Whether this NT may contribute to inflammation and the metabolic derangements associated with body weight gain remains to be elucidated.     

Circulating concentrations of asymmetrical dimethyl-<Emphasis Type="SmallCaps">L</Emphasis>-arginine are increased in women with previous gestational diabetes

AIMS/HYPOTHESIS: The concentration of asymmetrical dimethyl- L-arginine (ADMA), an endogenous inhibitor of the nitric oxide synthase, is increased in patients at risk or with cardiovascular disease. We have investigated ADMA concentrations in women with a history of gestational diabetes (GDM), who could develop endothelial dysfunction and Type II (non-insulin-dependent) diabetes mellitus after delivery, and in healthy control subjects. METHODS: Previous GDM patients were grouped according to their BMI as obese (> or =25 kg/m(2), n=46) or non-adipose (<25 kg/m(2), n=31). Serum samples were taken 14 to 16 weeks after delivery and after 1 year. The control group comprised 17 healthy women (BMI<25 kg/m(2)). ADMA concentrations were analysed by high performance liquid chromatography. RESULTS: ADMA concentrations were comparable between obese and non-adipose GDM patients (0.58+/-0.02 and 0.57+/-0.02 micro mol/l, respectively), and higher than in the control group (0.47+/-0.03 micro mol/l; p<0.006). Insulin resistance as estimated by the insulin sensitivity index was more frequent among the obese than the non-adipose GDM women (p<0.05) and control subjects (p<0.05, both). No change in ADMA concentrations was found after 1 year in women with GDM. There was only a slight correlation between ADMA and BMI (r=0.26, p<0.02), triglycerides (r=0.29, p<0.004), or fasting plasma glucose (r=0.21, p<0.05), and not with the insulin sensitivity index or other parameters. In a multiple regression analysis ADMA serum concentrations were only associated with triglycerides. CONCLUSION/INTERPRETATION: Circulating ADMA concentrations are increased in normoglycaemic women with previous GDM. This increase is independent from other risk factors or surrogate markers for diabetes or cardiovascular events.     

Serum leptin and regional cerebral blood flow during exposure to food in obese and normal-weight women

Leptin is an adipocyte-derived product of the ob gene thought to be involved in the regulation of eating. Receptors for leptin have been found in multiple regions in the brain. In particular, hypothalamic receptors seem to be of fundamental importance for the biological effects of leptin. However, the association of leptin with cerebral function in humans has not been studied. Therefore, in order to assess the possible functional relationships between leptin and cerebral activity in humans, simultaneous serum leptin and regional cerebral blood flow (rCBF) measurements were made in 10 obese [BMI 33.5 (29.3-39.1) kg/m2] and 12 normal-weight [BMI 22.2 (20.3-24.6) kg/m2] women during exposure to food. The rCBF measurements were performed by 99mTc-ethyl-cysteine-dimer single photon emission computed tomography. A strong inverse association was observed between the leptin and rCBF of hypothalamus during the exposure to food in the obese (r = -0.73, p = 0.02, n = 10), but not in the normal-weight subjects (r = 0.22, p = 0.48, n = 12). This suggests that the association of leptin with cerebral activity could be different in obese and normal-weight women; depressed activity of hypothalamic neurones in response to the high peripheral leptin concentration could be postulated to occur in obese women during exposure to food.     

Elevated serum levels of tumor necrosis factor alpha in normal-weight women with polycystic ovary syndrome

Since an increase in tumor necrosis factor alpha (TNFalpha) expression has been associated with insulin resistance, this study was undertaken to determine the status of circulating TNFalpha and the relationship of TNFalpha with insulin levels, body weight, or both in women with polycystic ovary syndrome (PCOS). Fasting serum samples were analyzed in 34 subjects with PCOS, of whom 22 were obese (body mass index [BMI]>27 kg/m2), and in 40 normal control women, of whom 20 were obese. Women with PCOS exhibited a significantly (P<.02) higher mean serum TNFalpha concentration compared with the controls. The serum TNFalpha level and BMI were directly correlated in women with PCOS (r=.48, P<.005) and highly correlated in controls (r=.78, P<.001). When subjects were classified by body weight, the mean serum TNFalpha concentration was significantly (P<.001) elevated in normal-weight women with PCOS compared with normal-weight controls. On the other hand, mean serum TNFalpha concentrations in obese women with PCOS and obese controls were similar and significantly (P<.02) higher than in normal-weight women with PCOS. A direct correlation between serum fasting insulin and TNFalpha was evident in controls (r=.35, P<.03), but not in women with PCOS. However, in the subgroup of obese women with PCOS, fasting insulin directly correlated (r=.49, P<.03) with TNFalpha and the median fasting serum insulin concentration was significantly (P<.05) higher compared with the level in normal-weight women with PCOS and all controls. Fasting insulin and TNFalpha were no longer correlated in controls as a group and in obese women with PCOS when controlling for body weight. Serum TNFalpha did not correlate with luteinizing hormone (LH), testosterone (T), or dehydroepiandrosterone sulfate (DHEAS) in women with PCOS. However, serum insulin was significantly correlated (r=.49, P<.0004) with T and the BMI exhibited a trend for correlation with serum T (r=.33, P=.05) in women with PCOS. Finally, the mean serum LH concentration was significantly (P<.02) higher in normal-weight women with PCOS versus obese women with PCOS, and serum LH levels exhibited a trend for an inverse correlation with the BMI (r=.31, P=.09) in women with PCOS. We conclude that (1) serum TNFalpha is increased in normal-weight women with PCOS and is even higher in obese individuals regardless of whether they have PCOS; (2) factors other than obesity are the cause of elevated serum TNFalpha in normal-weight women with PCOS; and (3) whereas increased circulating TNFalpha may mediate insulin resistance in obesity, which may in turn promote hyperandrogenism in obese women with PCOS, it remains to be demonstrated whether this is also the case in normal-weight women with PCOS.     

血清胰淀素、ADMA水平与代谢综合征的相关性

测定代谢综合征（MS）患者血清胰淀素和非对称二甲醛精氨酸（ADMA）水平,探讨两者的相关性及二者对MS的影响。方法：70例患者和体检对象根据其存在MS组分的个数分为非MS组（MS组分0~1个,20例）、MS高危组（MS组分2个,23例）和MS组（MS组分〉2个,27例）。分别测定空腹血糖、血脂、胰岛素、腰臀比（WHR）、体重指数（BMI）等指标,同时测定血清胰淀素、ADMA的水平。结果：与非MS组比较,MS高危组,MS组血清胰淀素[（0.41±0.04）g/L比（0.46±0.06）g/L比（0.49±0.06）g/L]、ADMA[（1.28±0.06）μg/L比（1.46±0.07）μg/L比（1.51±0.08）μg/L]的水平明显升高（P〈0.05）,且MS组明显高于MS高危组（P均〈0.05）。Pearson相关分析表明,血清胰淀素与甘油三酯（TG）、空腹胰岛素（FINS）、BMI、WHR、胰岛素抵抗指数（IRI）、ADMA呈正相关性（r=0.441~0.563,P均〈0.05）;与高密度脂蛋白胆固醇（HDL-C）呈负相关（r=-0.461,P〈0.05）;ADMA与IRI、BMI、FINS呈正相关（r=0.445~0.483,P〈0.05）。Logistic回归分析显示胰淀素、BMI、ADMA、IRI是MS的独立危险因素（OR=5.573~7.169,P均〈0.05）。结论：血清胰淀素和非对称二甲醛精氨酸的表达与代谢综合征的发生有关,两者都是MS的独立危险因素。     

Influence of dietary fat ingestion on asymmetrical dimethylarginine in lean and obese human subjects

Background and AimsAsymmetrical dimethylarginine (ADMA) may contribute to hypertension and cardiovascular disease by decreasing NO formation. In diabetic patients, a high fat meal acutely increased plasma ADMA while impairing endothelial function. We hypothesized that chronic and acute increases in dietary fat intake augment ADMA also in lean and in obese subjects without diabetes.Methods and ResultsSeventeen lean and twelve obese volunteers were randomized to two weeks of isocaloric diets with approximately 20% or >40% calories from fat in a cross-over fashion. At the end of the high and low fat periods, volunteers received corresponding test meals. ADMA was measured by GC–MS/MS using a deuterated standard. Mean fasting plasma ADMA concentration was 0.52 (0.49–0.54; 95% CI) μmol/l in lean and 0.53 (0.50–0.55) μmol/l in obese subjects (p = 0.55). The two week high fat diet did not influence ADMA. Both test meals elicited a 6%increase in circulating ADMA in lean subjects. In obese subjects, plasma ADMA concentration did not change with the low fat meal, and decreased by approximately 4% with the high fat meal.ConclusionOur findings challenge the idea that obesity and dietary fat intake have a major effect on plasma ADMA, at least in subjects without overt cardiovascular and metabolic disease. This finding is important with regard to dietary recommendations for weight loss. Overestimation of the influence of dietary fat intake and obesity on circulating ADMA in previous reports was most likely due to methodological issues concerning ADMA measurements.     

Impaired flow-mediated vasodilatation and insulin resistance in type 2 diabetic patients with albuminuria

An elevated urinary albumin excretion is associated with an increased risk of cardiovascular disease due to atherosclerosis, but the pathophysiological mechanism underlying this association is poorly understood. We studied 217 diabetic patients, that is, 121 normoalbuminuric patients, 71 microalbuminuric patients, and 25 macroalbuminuric patients. We evaluated flow-mediated dilatation of brachial artery (%FMD, one endothelial function marker associated with endogenous NO production), von Willebrand factor (vWF, endothelial activation marker), high-sensitive CRP (hsCRP, a low-grade inflammation marker), asymmetric dimethyl arginine (ADMA, an endogenous inhibitor of NO synthesis), and insulin sensitivity by steady-state plasma glucose method. %FMD was apparently decreased in microalbuminuric and macroalbuminuric patients compared with normoalbuminuric patients (p<0.001). Moreover, %FMD was significantly correlated with the degree of albuminuria (r=-0.38, p<0.05). On the other hand, vWF and hsCRP did not show significant difference between normoalbuminuric patients and microalbuminuric patients. In diabetic patients with macroalbuminuria, ADMA was significantly elevated compared to those with normoalbuminuria. Insulin sensitivity was significantly associated with urinary albumin excretion rate. These results suggested that endothelial dysfunction which may be due to impaired NO production and insulin resistance underlie the association between diabetic nephropathy and atherosclerosis in diabetic patients.     

Relationship between serum resistin concentrations and insulin resistance in nonobese, obese, and obese diabetic subjects

Early reports suggested that resistin is associated with obesity and insulin resistance in rodents. However, subsequent studies have not supported these findings. To our knowledge, the present study is the first assessment in human subjects of serum resistin and insulin sensitivity by the insulin clamp technique. Thirty-eight nonobese subjects [age, 23 +/- 4 yr; body mass index (BMI), 25.4 +/- 4.3 kg/m(2)], 12 obese subjects (age, 54 +/- 8 yr; BMI, 33.0 +/- 2.5 kg/m(2)), and 22 obese subjects with type 2 diabetes (age, 59 +/- 7 yr; BMI, 34.0 +/- 2.4 kg/m(2)) were studied. Serum resistin concentrations were not different among nonobese (4.1 +/- 1.7 ng/ml), obese (4.2 +/- 1.6 ng/ml), and obese diabetic subjects (3.7 +/- 1.2 ng/ml), and were not significantly correlated to glucose disposal rate during a hyperinsulinemic glucose clamp across groups. Serum resistin was, however, inversely related to insulin sensitivity in nonobese subjects only (r = -0.35; P = 0.05), although this association was lost after adjusting for percent body fat. Serum resistin was not related to percent fat, BMI, or fat cell size. A strong correlation was observed between serum resistin and resistin mRNA expression from abdominal sc adipose tissue in a separate group of obese subjects (r = 0.62; P < 0.01; n = 56). Although the exact function of resistin is unknown, we demonstrated only a weak relationship between resistin and insulin sensitivity in nonobese subjects, indicating that resistin is unlikely to be a major link between obesity and insulin resistance in humans.     

Serum concentrations of nitric oxide, tumor necrosis factor (TNF)-alpha and TNF soluble receptors in women with overweight and obesity

The aims of the present study was to examine how overweight and obesity affect serum concentrations nitric oxide (NO) metabolites and to determine whether there is association between serum concentrations tumor necrosis factor (TNF)-alpha and TNF soluble receptors (sTNF-R) in subjects with overweight and obesity. The study groups involved 154 women: 102 obese (81 obese with body mass index [BMI] 30 to 40 kg/m2 and 21 obese with BMI > 40 kg/m2), 24 overweight patients, and 28 lean controls. Serum concentrations of NO metabolites and of TNF-alpha and its soluble receptors (sTNF-R1, sTNFR-2) were measured by enzyme-linked immunosorbent assay (ELISA) kits. Serum concentration of insulin was measured by radioimmunoassay (RIA). Plasma glucose, cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglicerydes were determined by enzymatic procedure. Body composition was determined by impedance analysis using Bodystat (Douglas, British Isles). Serum concentrations of NO in the overweight group (35.1 +/- 12.1 micromol/L) and the obese groups with BMI 30 to 40 kg/m2 (32.8 +/- 9.3 micromol/L) and with BMI greater than 40 kg/m2 (33.3 +/- 8.5 micromol/L) were significantly higher when compared to controls (28.2 +/- 8.1 micromol/L): P < .05; P < .01, and P < .01, respectively. There was no difference in levels of NO between the overweight group and both obese groups. Serum concentration of TNF-alpha was also significantly higher in the group with overweight (6.5 +/- 3.1 pg/mL), in the obese group with BMI 30 to 40 kg/m2 (6.8 +/- 3.1 pg/mL), and in the obese group with BMI greater than 40 kg/m2 (7.4 +/- 2.6 pg/mL) when compared to controls (2.9 +/- 2.2 pg/mL): P < .00005; P < .00005, and P < .0000001, respectively. However, serum concentrations of sTNF-R1 and -R2 did not differ significantly between the overweight group, both obese groups, and controls. In conclusion, we observed increased serum concentrations of TNF-alpha and NO in overweight and obese women. It seems that there is an association between serum concentrations of TNF-alpha and NO; however, this relationship depends on the degree of obesity.     

Cephalic-phase insulin in obese and normal-weight men: Relation to postprandial insulin

Cephalic-phase insulin release (CPIR) and its relation to postprandial insulin release were examined in 18 normal-weight and 15 obese men. When the insulin data were expressed as absolute differences from baseline values, obese subjects exhibited significantly greater CPIR than normal-weight subjects (normals, 8.7 ± 2.1 μU mL/10 min; obese, 13.4 ± 4.3 μU mL/10 min; P < .01). Obese subjects were then separated into groups depending on their fasting insulin levels. This showed that only those subjects with elevated fasting insulin levels exhibited greater CPIR than normal subjects, and suggested that previous reports of exaggerated CPIR in the obese are merely a reflection of a basal hypersecretion of insulin. However, when insulin values were expressed as percentages of baseline, no significant differences between normal-weight and obese subjects were found, although a trend toward an attenuated response was observed in the obese group as a whole (normals, 81.6 ± 19.1 μU mL/10 min; obese, 51.3 ± 16.1 μU mL/10 min). A significant correlation between cephalic-phase and postprandial insulin release was found in normal-weight subjects (r = .62, P < .05), but not in obese subjects (r = .02, P < .9).     

Increased circulating concentrations of asymmetric dimethylarginine (ADMA) in white coat hypertension

Elevated plasma levels of the endogenous nitric oxide (NO) synthase inhibitor asymmetric dimethylarginine (ADMA) contribute to endothelial dysfunction and seem to be a predictor for cardiovascular mortality. Elevated ADMA plasma concentrations have been demonstrated in patients with hypertension. However, the plasma concentrations of ADMA in white coat hypertension (WCH) has not been previously studied. The aim of this study was to evaluate ADMA in WCH and compare with normotensive (NT) and hypertensive (HT) patients. We also evaluated the relation between ADMA and NO in these three groups. For this purpose, 34 NT, 34 white coat hypertensive (clinical hypertension and ambulatory daytime blood pressure <135/85 mmHg) and 34 HT patients were recruited in this study. The subjects were matched for age, gender, body mass index (BMI) and the patients with smoking habit, dyslipidaemia and diabetes mellitus were excluded. The ADMA levels were determined by high performance liquid chromatography. Plasma ADMA levels were significantly higher in WCH group than in the NT group (3.21+/-0.49 micromol/l vs 2.84+/-0.58 micromol/l, P=0.046). It was significantly higher in the HT group than in the NTs (4.24+/-0.38 micromol/l, P<0.001). There was also a significant difference between the HT and WCH groups (P<0.001). The WCH subjects had significantly higher levels of NO than the HTs (41.68+/-2.23 vs 32.18+/-2.68 micromol/l; P<0.001) and significantly lower values than the NTs (48.24+/-4.29 micromol/l; P<0.001). In WCH and HT group, there was a negative correlation between ADMA and NO (r=-0.515, P=0.003 and r=-0.389, P=0.034, respectively). In NT subjects, there was no correlation between these two parameters (r=-0.287, P=0.124). The correlation between ADMA and NO was stronger in WCH group than in HT group. Although NO levels in HT patients were lower than WCHs and ADMA levels were higher in HT patients than WCHs, the negative correlation of these two parameters were more pronounced in WCH group. Decreased NO and increased ADMA levels in WCH may indicate endothelial dysfunction. Our data indicate also that WCH represent an intermediate group between NT and HT when endothelial dysfunction is concerned.     

Familial obesity, sympathetic activation and blood pressure level.

This study was conducted to evaluate the relative contributions of existing obesity and a family history of obesity (FHOB) to blood pressure (BP) level, sympathetic activity, plasma leptin and insulin levels in young men without a family history of hypertension. The study was of "four-corner" design according to body mass index (BMI). A positive FHOB (FHOB+) was defined as both parents being obese (BMI >26.0 kg/m2), and a negative FHOB (FHOB-) was defined as both parents being lean (BMI <22.0 kg/ m2). The cutoff limits of BP for the subjects and their parents enrolled in present study was defined as a supine reading of <140/90 mmHg. In 12 lean young subjects with FHOB-, 9 obese young subjects with FHOB-, 8 lean young subjects with FHOB+ and 16 obese young subjects with FHOB+, BMI, BP, plasma norepinephrine (NE), insulin and leptin were measured. All subjects were men and non-diabetic. Obese subjects, irrespective of FHOB, had higher levels of BMI, BP, plasma NE, leptin and insulin compared to lean subjects. In subjects with FHOB+, regardless of their current degree of adiposity, there was a higher level of BP and plasma NE than in subjects with FHOB-. In lean subjects, FHOB+ was associated with a higher plasma NE level and BP, but similar levels of plasma leptin and insulin were found when compared with FHOB- subjects. These results suggest that existing obesity and a positive family history of obesity appear to have an association with sympathetic overactivity and BP elevation.     

Cognitive function in normal-weight, overweight, and obese older adults: an analysis of the Advanced Cognitive Training for Independent and Vital Elderly cohort

OBJECTIVES: To assess how elevated body mass index (BMI) affects cognitive function in elderly people. DESIGN: Cross-sectional study. SETTING: Data for this cross-sectional study were taken from a multicenter randomized controlled trial, the Advanced Cognitive Training for Independent and Vital Elderly trial. PARTICIPANTS: The analytic sample included 2,684 normal-weight, overweight, or obese subjects aged 65 to 94. MEASUREMENTS: Evaluation of cognitive abilities was performed in several domains: global cognition, memory, reasoning, and speed of processing. Cross-sectional association between body weight status and cognitive functions was analyzed using multiple linear regression. RESULTS: Overweight subjects had better performance on a reasoning task (beta=0.23, standard error (SE)=0.11, P=.04) and the Useful Field of View (UFOV) measure (beta=-39.46, SE=12.95, P=.002), a test of visuospatial speed of processing, after controlling for age, sex, race, years of education, intervention group, study site, and cardiovascular risk factors. Subjects with class I (BMI 30.0-34.9 kg/m2) and class II (BMI>35.0 kg/m2) obesity had better UFOV measure scores (beta=-38.98, SE=14.77, P=.008; beta=-35.75, SE=17.65, and P=.04, respectively) in the multivariate model than normal-weight subjects. The relationships between BMI and individual cognitive domains were nonlinear. CONCLUSION: Overweight participants had better cognitive performance in terms of reasoning and visuospatial speed of processing than normal-weight participants. Obesity was associated with better performance in visuospatial speed of processing than normal weight. The relationship between BMI and cognitive function should be studied prospectively.     

Platelet nitric oxide production and IR: relation with obesity and hypertriglyceridemia

Background and AimThree NOS isoforms are responsible for nitric oxide production in various tissues. Endothelial constitutive NOS is expressed in vascular endothelium and in platelets, contributing to vascular tone regulation and platelet aggregation.The aim of the present work was to examine eNOS polymorphism, to find a correlation with platelet NO production and degree of insulin resistance (IR) in non-diabetic subjects and in patients affected by type 2 diabetes.Methods and ResultsSeventy-one non-diabetic subjects and 37 patients affected by Type 2 diabetes were recruited. The subjects were subdivided into 3 groups as cut-off for the definition of an insulin resistant state: IR non-diabetic subjects, insulin sensitive subjects, and insulin-resistant patients affected by Type 2 diabetes.Plasma glyco-metabolic parameters, platelet nitric oxide production, endothelial nitric oxide synthase (eNOS) gene polymorphism were measured in all subjects enrolled. Significant differences between groups were found in BMI, fasting glycaemia, fructosamine and HbA_1c, triglycerides and HDL cholesterol levels.Evaluating all the subjects, platelet NO production was significantly related with BMI, waist circumference, and triglycerides concentrations, thus suggesting an association between increased platelet NO production, obesity and hypertriglyceridemia, independent of the degree of insulin-resistance.ConclusionThe modified platelet NO synthesis does not seem to be due to eNOS Glu298Asp polymorphism, while it can be hypothesized that it is caused by an iNOS induction, present in obesity, hypertriglyceridemia and in type 2 diabetes.     

Elevations of plasma methylarginines in obesity and ageing are related to insulin sensitivity and rates of protein turnover

Aims/hypothesis Increased circulating methylarginines (MA) have been linked to the metabolic syndrome to explain endothelial dysfunction and cardiovascular disease risk. Proteins that contain MA are regulatory and release them during catabolism. We hypothesised that increased protein turnover in insulin-resistant states contributes to an increase in circulating MA. Matwerials and methods We performed hyperinsulinaemic, euglycaemic, and isoaminoacidaemic experiments on 49 lean, obese and elderly subjects, with measurements of the kinetics of glucose and protein metabolism. Plasma MA, i.e. asymmetrical dimethylarginine (ADMA), symmetrical dimethylarginine (SDMA), and N -monomethyl-l-arginine (NMMA), lipids and body composition were measured. Results Insulin resistance of glucose and protein metabolism occurred in obese and elderly subjects. ADMA concentrations were 29 to 120% higher in obese and 34% higher in elderly than in lean subjects. SDMA were 34 and 20% higher in obese than in lean and than in elderly subjects, respectively. NMMA were 32% higher in obese than in lean subjects. ADMA differed by sex, being higher in men, namely by 1.75× in obese men and by 1.27× in elderly men. Postabsorptive ADMA (r=0.71), SDMA (r=0.46), and NMMA (r=0.31) correlated (all p<0.05) with rates of protein flux. All three MA correlated negatively with clamp glucose infusion rates and uptake (p<0.001). ADMA and SDMA correlated negatively with net protein synthesis and clamp amino acid infusion rates (p<0.05). All MA also correlated with adiposity indices and fasting insulin and triglycerides (p<0.05). Conclusions/interpretation Obesity, sex and ageing affect MA. Elevations of the three MA in obese, and of ADMA in elderly men, are related to increased protein turnover and to lesser insulin sensitivity of protein metabolism. These interrelationships might amplify insulin resistance and endothelial dysfunction.     

Nitric oxide production is paradoxically decreased after weight reduction surgery in morbid obesity patients

Obesity is associated with vascular endothelial cell dysfunction (ECD). Studies on nitric oxide (NO) production of vascular system in these subjects may help delineate the pathogenesis of obesity-associated ECD. In this study, we recruited 69 severely obese patients who were treated with gastric partition surgery for weight reduction and 69 matched healthy controls for comparison. The following parameters were obtained in the healthy control subjects and in the obese subjects both before and after gastric partition surgery: body mass index, blood pressure, serum lipids, high sensitivity C-reactive protein (hs-CRP), adiponectin, total nitrite and nitrate (NO_x), and 8-iso-prostaglandin F2 (8-iso-PGF2), and insulin resistance index (as measured by homeostasis model assessment (HOMA-IR). At baseline, serum lipids, glucose, insulin, hs-CRP and 8-iso-PGF2 and HOMA-IR were all higher while adiponectin lower in the obese group than in the control group. The serum NO_x levels were not different between the two groups. In the obese subjects, the adiponectin levels were significantly elevated but NO_x markedly decreased after surgery. All other measurements, except for systolic blood pressure, were decreased after surgery. For healthy controls, the serum NO_x levels were negatively associated with HOMA-IR and positively associated with serum adiponectin levels as analyzed by multiple linear regression analysis. In obese patients, the baseline serum NO_x was positively associated with the serum TG levels. The changes of serum NO_x levels after weight reduction surgery were positively associated with the changes of body mass index and serum TG levels. These observations suggested that, in the extremely obese patients, there might be excessive production and/or inactivation of NO and, after weight reduction surgery, the NO production was down-regulated. In conclusion, in the severely obese patients, the apparently normal NO production might be due to over-expression of iNOS. After gastric partition surgery, the NO production was significantly decreased which might be reflecting the usual status of NO production in obese subjects. The positive correlation between NO_x and serum TG level might suggest that the metabolism of TG plays a role in the regulation of NO production.