Obese Control Subjects Research Articles

Dynamic Upper Airway Imaging during Wakefulness in Obese Subjects with and without Sleep Apnea.

Obesity is a major risk factor for obstructive sleep apnea. Although greater dimensional changes in the upper airway during wake respiration have been noted in patients with apnea compared with control subjects, whether these differences remain in the presence of obesity is unknown. To evaluate upper airway anatomic characteristics and airway compliance (distensibility) in obese subjects with obstructive sleep apnea compared with obese control subjects. Dynamic magnetic resonance imaging was performed in 157 obese subjects with apnea and 46 obese control subjects during wakefulness in the midsagittal and three axial upper airway regions (retropalatal, retroglossal, epiglottal). Differences in measurements between subjects with apnea and control subjects, and correlations with apnea-hypopnea index among subjects with apnea, were examined. Measurements included airway areas and linear dimensions. Subject-specific coefficients of variation were calculated to examine variability in airway size. Controlling for covariates, the retropalatal area during respiration was significantly smaller in subjects with apnea than control subjects, based on the average (P = 0.003), maximum (P = 0.004), and minimum (P = 0.001) airway area. Airway narrowing was observed in anteroposterior and lateral dimensions (adjusted P < 0.05). Results were similar in an age, sex, and body mass index-matched subsample. There were significant correlations between apnea-hypopnea index and dynamic measures of airway caliber in the retropalatal and retroglossal regions among subjects with apnea. Upper airway caliber during respiration was significantly narrower in obese subjects with apnea than obese control subjects in the retropalatal region. These findings provide further evidence that retropalatal airway narrowing plays an important role in the pathogenesis of obstructive sleep apnea in obese subjects.

Thyroid profile and LDH Isoenzymes as prognostic biomarkers for diabetic and/or obese subjects.

This study aimed to evaluate the levels of thyroid hormones and lactate dehydrogenase (LDH) isoenzymes in obese and/or diabetic patients. Forty male subjects categorized into four equal groups; group 1: Non obese control subjects, group 2: Subjects suffering from type 2 diabetes mellitus (T2DM), group 3: Obese subjects (BMI ≥ 30 kg/m2) and group 4: Subjects thatwere obese and had type 2 diabetes mellitus (T2DM). Liver, kidney, lipid, thyroid hormones, total LDH and LDH isoenzymes levels were determined. There was a significant increase of TSH level (p<0.001) in diabetic group as compared with control group and a highly significant increase of TSH was obtained in obese and obese diabetic groups versus control and diabetic patients. LDH 2 was also highly significantly decreased in obese and obese diabetic groups versus diabetic patients. Percentage of LDH 4 was significantly decreased in both diabetic and obese groups and not significantly changed in obese diabetic patients as compared with the control group. LDH 5 percentage showed very highly significant decrease in diabetic, obese and highly significant decrease in obese diabetic groups when compared with control subjects while it was not significantly changed in obese and obese diabetic groups as compared with diabetic patients. LDH isozymes can be used as valuable diagnostic markers for metabolic syndrome. This may help to explore the metabolic changes associated with obesity and diabetes complication and following up the complication of these abnormalities.

Hyperhomocysteinemia in polycystic ovary syndrome: decreased betaine-homocysteine methyltransferase and cystathionine β-synthase-mediated homocysteine metabolism

What are the metabolic characteristics of homocysteine in polycystic ovary syndrome (PCOS)? Homocysteine concentrations were determined in serum samples from non-obese and obese control subjects and PCOS patients. Homocysteine metabolism was studied in a rat model of PCOS established using dehydroepiandrosterone (DHEA) or DHEA in combination with a high-fat diet (HFD). It was shown that (i) serum homocysteine concentrations were greater in PCOS patients than in control subjects in the obese group (P < 0.05) and serum homocysteine concentrations were significantly higher in the obese group than in the non-obese group, regardless of PCOS status (both P < 0.05); (ii) serum homocysteine concentrations were significantly increased in DHEA + HFD-induced rats compared with controls (P < 0.05); (iii) when compared with the control group, mRNA concentrations of homocysteine metabolic enzymes Bhmt and Cbs were significantly reduced in the liver tissues of DHEA + HFD-induced rats (both P < 0.0001); (iv) when compared with the control group, there was a significant decrease in the methylation concentrations of the Cbs (P < 0.05) and Bhmt (P < 0.05 and P < 0.0001) promoter in the DHEA + HFD group. The methylation patterns, together with previous data, indicate that hypomethylated promoter-mediated transcriptional activation of Bhmt and Cbs might be a defence mechanism against PCOS-related hyperhomocysteinemia. These findings indicate that decreased liver Bhmt and Cbs-mediated homocysteine metabolism might have a role in hyperhomocysteinemia in PCOS and provides further evidence for a potential role of decreased liver function in PCOS.

Comparative effects of small intestinal glucose on blood pressure, heart rate, and noradrenaline responses in obese and healthy subjects.

Meal consumption leads to an increase in sympathetic output to compensate for hemodynamic changes and maintain blood pressure (BP). Obesity is associated with a blunting of the sympathetic response to meal ingestion, but interpretation of studies investigating these responses is compromised by their failure to account for the rate of gastric emptying, which is an important determinant of postprandial cardiovascular and sympathetic responses and, in both health and obesity, exhibits a wide interindividual variation. We sought to determine the effects of intraduodenal glucose infusion, bypassing gastric emptying, on BP, heart rate (HR), and noradrenaline responses in obese and healthy control subjects. 12 obese subjects (age 36.6 ± 3.9 years, body mass index (BMI) 36.1 ± 1.3 kg/m2) and 23 controls (age 27.8 ± 2.4 years, BMI 22.4 ± 0.5 kg/m2) received intraduodenal infusions of glucose at 1 or 3 kcal/min, or saline, for 60 min (t = 0–60 min), followed by intraduodenal saline (t = 60–120 min). BP and HR were measured with an automatic cuff, and blood samples collected for measurement of plasma noradrenaline. Intraduodenal glucose at 1 kcal/min was associated with a fall in diastolic BP in the control subjects only (P < 0.01), with no change in systolic BP, HR or noradrenaline in either group. In both groups, intraduodenal glucose at 3 kcal/min was associated with a fall in diastolic (P < 0.01), but not systolic, BP, and rises in HR (P < 0.001) and plasma noradrenaline (P < 0.01), with no difference in responses between the groups. We conclude that cardiovascular and sympathetic responses to intraduodenal glucose infusion are comparable between obese and control subjects, and dependent on the rate of glucose delivery.

Intramuscular triglyceride synthesis: importance in muscle lipid partitioning in humans.

Intramuscular triglyceride (IMTG) concentration is elevated in insulin-resistant individuals and was once thought to promote insulin resistance. However, endurance-trained athletes have equivalent concentration of IMTG compared with individuals with type 2 diabetes, and have very low risk of diabetes, termed the "athlete's paradox." We now know that IMTG synthesis is positively related to insulin sensitivity, but the exact mechanisms for this are unclear. To understand the relationship between IMTG synthesis and insulin sensitivity, we measured IMTG synthesis in obese control subjects, endurance-trained athletes, and individuals with type 2 diabetes during rest, exercise, and recovery. IMTG synthesis rates were positively related to insulin sensitivity, cytosolic accumulation of DAG, and decreased accumulation of C18:0 ceramide and glucosylceramide. Greater rates of IMTG synthesis in athletes were not explained by alterations in FFA concentration, DGAT1 mRNA expression, or protein content. IMTG synthesis during exercise in Ob and T2D indicate utilization as a fuel despite unchanged content, whereas IMTG concentration decreased during exercise in athletes. mRNA expression for genes involved in lipid desaturation and IMTG synthesis were increased after exercise and recovery. Further, in a subset of individuals, exercise decreased cytosolic and membrane di-saturated DAG content, which may help explain insulin sensitization after acute exercise. These data suggest IMTG synthesis rates may influence insulin sensitivity by altering intracellular lipid localization, and decreasing specific ceramide species that promote insulin resistance.

Gene expression analysis identify a metabolic and cell function alterations as a hallmark of obesity without metabolic syndrome in peripheral blood, a pilot study

Understanding molecular basis involved in overweight is an important first step in developing therapeutic pathways against excess in body weight gain. The purpose of our pilot study was to evaluatethe gene expression profiles in the peripheral blood of obese patients without other metabolic complications. A sample of 17 obese patients without metabolic syndrome and 15 non obese control subjects was evaluated in a prospective way. Following 'One-Color Microarray-Based Gene Expression Analysis' protocol Version 5.7 (Agilent p/n 4140-90040), cRNA was hybridized with Whole Human Genome Oligo Microarray Kit (Agilent p/n G2519F-014850) containing 41,000+ unique human genes and transcripts. The average age of the study group was 43.6±19.7 years with a sex distribution of 64.7% females and 35.3% males. No statistical differences were detected with healthy controls 41.9±12.3 years with a sex distribution of 70% females and 30% males. Obese patients showed 1436 genes that were differentially expressed compared to control group. Ingenuity Pathway Analysis showed that these genes participated in 13 different categories related to metabolism and cellular functions. In the gene set of cellular function, the most important genes were C-terminal region of Nel-like molecule 1 protein (NELL1) and Pigment epithelium-derived factor (SPEDF), both genes were over-expressed. In the gene set of metabolism, insulin growth factor type 1 (IGF1), ApoA5 (apolipoprotein subtype 5), Foxo4 (Forkhead transcription factor 4), ADIPOR1 (receptor of adiponectin type 1) and AQP7 (aquaporin channel proteins7) were over expressed. Moreover, PIKFYVE (PtdIns(3) P 5-kinase), and ROCK-2 (rho-kinase II) were under expressed. We showed that PBMCs from obese subjects presented significant changes in gene expression, exhibiting 1436 differentially expressed genes compared to PBMCs from non-obese subjects. Furthermore, our data showed a number of genes involved in relevant processes implicated in metabolism, with genes presenting high fold-change values (up-regulation and down regulation) associated with lipid, carbohydrate and protein metabolism.

Abstract P308: Physical Activity is Associated With Lower Atherosclerotic Risk and Arterial Stiffness in Youth

Introduction: The prevalence of cardiovascular (CV) risk factors in young people has increased related to the pediatric obesity epidemic. An association between physical activity (PA) and target organ damage has been firmly established in adults, and such damage confers increased CV event risk. There is an urgent need to implement prevention strategies for CV disease in youth. Promoting PA holds promise in this regard. However, in order to be a useful marker, PA needs to be quantified accurately and feasibly in the clinical setting, and its relationship to preclinical CV disease in youth needs to be understood. Objective: We aimed to 1) examine the relationship between a subjective measure of PA and an objective measure in a young cohort, 2) determine the association of PA and other CV risk factors, and 3) test the hypothesis that PA is an independent determinant of target organ damage. Methods: Adolescents and young adults were recruited from an ongoing study of the effects of risk factors on CV aging. At baseline adolescents with type 2 diabetes mellitus were matched by age, sex, and race to lean and obese control subjects without diabetes. These analyses were performed at 5 years follow-up on 249 subjects (mean age 22 ± 3.9 years). PA was measured with the International Physical Activity Questionnaire (IPAQ) and the Actical accelerometer. Target organ damage was assessed with echocardiography and vascular structure and function testing. Subjects were stratified into tertiles of average PA with the lean group as the standard. Differences in endpoints by PA tertile were tested by analysis of variance and χ2 tests. General linear models were constructed and used to test for independent associations. Results: Responses to the IPAQ differed greatly from objective accelerometry. There was a weak trend toward increased CV risk factors and target organ damage in those with the lowest IPAQ scores. When subjects were stratified into tertiles of by accelerometry the less active subjects had significantly worse CV risk profiles as indicated by higher Pathobiological Determinants of Atherosclerosis in Youth (PDAY) scores, and more signs of target organ damage including stiffer arteries as indicated by greater carotid-femoral pulse wave velocities. These differences did not reach statistical significance when adjusted for metabolic variables. Conclusion: PA is associated with CV risk factor clustering and target organ damage in young people. Measuring PA in this population is feasible, but has limitations. This study confirms the utility of PA in predicting the presence of target organ damage. Our study is the first to demonstrate a negative, cross-sectional relationship between PA and PDAY score. Future opportunities for research include examining the contribution of different levels of PA on CV aging as well as the effect of increasing PA over time.

Rare Loss-of-Function Variants in NPC1 Predispose to Human Obesity.

Some Shanghai Clinical Center f a role of Niemann-Pick type C1 (NPC1) for obesity traits. However, whether the loss-of-function mutations in NPC1 cause adiposity in humans remains unknown. We recruited 25 probands with rare autosomal-recessive Niemann-Pick type C (NP-C) disease and their parents in assessment of the effect of heterozygous NPC1 mutations on adiposity. We found that male NPC1+/- carriers had a significantly higher BMI than matched control subjects or the whole population-based control subjects. Consistently, male NPC1+/- mice had increased fat storage while eating a high-fat diet. We further conducted an in-depth assessment of rare variants in the NPC1 gene in young, severely obese subjects and lean control subjects and identified 17 rare nonsynonymous/frameshift variants in NPC1 (minor allele frequency <1%) that were significantly associated with an increased risk of obesity (3.40% vs. 0.73%, respectively, in obese patients and control subjects, P = 0.0008, odds ratio = 4.8, 95% CI 1.7-13.2), indicating that rare NPC1 variants were enriched in young, morbidly obese Chinese subjects. Importantly, participants carrying rare variants with severely damaged cholesterol-transporting ability had more fat accumulation than those with mild/no damage rare variants. In summary, rare loss-of-function NPC1 mutations were identified as being associated with human adiposity with a high penetrance, providing potential therapeutic interventions for obesity in addition to the role of NPC1 in the familial NP-C disease.

Bariatric Surgery Enhances Splanchnic Vascular Responses in Patients With Type 2 Diabetes

Bariatric surgery results in notable weight loss and alleviates hyperglycemia in patients with type 2 diabetes (T2D). We aimed to characterize the vascular effects of a mixed meal and infusion of exogenous glucose-dependent insulinotropic polypeptide (GIP) in the splanchnic region in 10 obese patients with T2D before and after bariatric surgery and in 10 lean control subjects. The experiments were carried out on two separate days. Pancreatic and intestinal blood flow (BF) were measured at baseline, 20 min, and 50 min with 15O-water by using positron emission tomography and MRI. Before surgery, pancreatic and intestinal BF responses to a mixed meal did not differ between obese and lean control subjects. Compared with presurgery, the mixed meal induced a greater increase in plasma glucose, insulin, and GIP concentrations after surgery, which was accompanied by a marked augmentation of pancreatic and intestinal BF responses. GIP infusion decreased pancreatic but increased small intestinal BF similarly in all groups both before and after surgery. Taken together, these results demonstrate that bariatric surgery leads to enhanced splanchnic vascular responses as a likely consequence of rapid glucose appearance and GIP hypersecretion.

Obesity and type 2 diabetes are associated with elevated PCSK9 levels in young women.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of low-density lipoprotein cholesterol and cardiovascular disease risk, and is an emerging therapeutic target. We compared serum PCSK9 levels in young adults, with and without type 2 diabetes. Cross-sectional analysis was conducted in a cohort, aged 15 to 26 years, in Cincinnati, OH, from 2005 to 2010. Serum PCSK9 levels were measured in 94 youth with type 2 diabetes, 93 obese control subjects, and 99 lean control subjects. Correlative analyses were conducted to determine significant covariates of PCSK9 by group and sex, and multivariate linear regression models were used to study the independent determinants of PCSK9. In females, PCSK9 levels were significantly increased in the obese and type 2 diabetes subjects relative to the lean controls (P < .01). Moreover, PCSK9 was positively correlated with multiple metabolic parameters in females: body mass index, systolic blood pressure, fasting glucose, fasting insulin, and C-reactive protein levels (P ≤ .02). In males, PCSK9 levels were decreased overall compared with females (P = .03), and did not differ between the lean, obese, or type 2 diabetes groups. Obesity and type 2 diabetes were associated with significantly higher levels of PCSK9 in young women, but not in young men. These data suggest that sex could modify the effects of obesity and diabetes on PCSK9 in young adults.

Bariatric Surgery and the Risk of New-Onset Atrial Fibrillation in Swedish Obese Subjects

BackgroundObesity is a risk factor for atrial fibrillation, which in turn is associated with stroke, heart failure, and increased all-cause mortality. ObjectivesThe authors investigated whether weight loss through bariatric surgery may reduce the risk of new-onset atrial fibrillation. MethodsSOS (Swedish Obese Subjects) is a prospective matched cohort study conducted at 25 surgical departments and 480 primary healthcare centers in Sweden. The cohort was recruited between 1987 and 2001. Among 4,021 obese individuals with sinus rhythm and no history of atrial fibrillation, 2,000 underwent bariatric surgery (surgery group), and 2,021 matched obese control subjects received usual care (control group). The outcome, first-time atrial fibrillation, was ascertained by crosschecking the SOS database with the Swedish National Patient Register on inpatient and outpatient diagnosis codes. ResultsDuring a median follow-up of 19 years, first time atrial fibrillation occurred in 247 patients (12.4%) in the surgical group, and in 340 (16.8%) control subjects. The risk of developing atrial fibrillation was 29% lower in the surgery group versus the control group (hazard ratio: 0.71; 95% confidence interval: 0.60 to 0.83; p < 0.001). Younger individuals benefited more from surgical intervention than those who were older (p value for interaction 0.001). Also, those with a high diastolic blood pressure benefitted more from surgery than did those with a low diastolic blood pressure (p for interaction = 0.028). ConclusionsCompared with usual care, weight loss through bariatric surgery reduced the risk of atrial fibrillation among persons being treated for severe obesity. The risk reduction was more apparent in younger people and in those with higher blood pressure.

Faecalibacterium prausnitzii phylotypes in type two diabetic, obese, and lean control subjects.

Faecalibacterium prausnitzii is one of the main butyrate producers in the healthy human gut. Information on its genetic diversity is lacking, although two genetic phylotypes have been differentiated. In the present study, F. prausnitzii phylotypes were examined in faeces of obese and type two diabetes with similar eating behaviour compared to a lean control group. The purpose of the study was to analyse if an excessive butyrate production induced by different F. prausnitzii phylotypes discriminates between obese developing type two diabetes or not. The faecal samples were analysed for the total abundance of F. prausnitzii 16S rRNA copies, fragment lengths polymorphism, high resolution melt curve analysis (HRM) and the butyryl-CoA:acetate CoA-transferase gene copies and melt curve variances. The diabetic group was found to differ significantly from the lean control group in the results of qPCR, butyryl-CoA:acetyate CoA-transferase gene melt curve, and HRM. F. prausnitzii phylotypes differed in obese with and without developed diabetes type two. Different phylotypes of F. prausnitzii may lead to differences in the inflammatory genesis in the host. F. prausnitzii phylotypes may have an influence on developing type two diabetes and might also act as starting points for prevention and therapy of obesity associated disease.

Mechanism of Gastroesophageal Reflux in Obstructive Sleep Apnea: Airway Obstruction or Obesity?

This is the first study to compare reflux events during wake and sleep in obese and non-obese individuals with obstructive sleep apnea (OSA) and obese individuals without OSA. The primary aim of the study was to investigate any additive effect of OSA on gastroesophageal reflux (GER) above that of obesity. Twenty obese individuals (body mass index, BMI > 30 kg/m(2)), 9 non-obese individuals (BMI < 30 kg/m(2)) with moderate-to-severe OSA, and 17 obese control subjects (BMI > 30 kg/m(2)) underwent high-resolution esophageal manometry, 24-h esophageal pH-impedance monitoring, and in-laboratory polysomnography. Mean body mass index was 40 ± 6 and 27 ± 4 kg/m(2) for the obese and non-obese OSA groups, respectively, and 34 ± 5 kg/m(2) for the obese control group. Apnea-hypopnea index (AHI) was 50 ± 30 and 30 ± 25 per hour for the obese and non-obese OSA groups (p > 0.05), significantly higher than that of the obese control group (3 ± 3 per hour, p < 0.05). The two obese groups did not show any significant differences in the total number of acidic reflux events (41 ± 20 vs 28 ± 16); however, the obese OSA group had a greater number of acidic reflux events compared to the non-obese OSA group (22 ± 12 events, p < 0.05). In multivariate analysis, BMI significantly predicted number of acidic reflux events (r(2) = 0.16, p = 0.01) during the 24-h period; however, AHI showed no significant association with any measure of GER severity. This study confirms an important role for obesity, rather than OSA per se in the relationship between OSA and GER.

Systemic inflammation and higher perception of dyspnea mimicking asthma in obese subjects

There are a variable number of obese subjects with self-reported diagnosis of asthma but without current or previous evidence of airflow limitation, bronchial reversibility, or airway hyperresponsiveness (misdiagnosed asthma). However, the mechanisms of asthma-like symptoms in obesity remain unclear. We sought to evaluate the perception of dyspnea during bronchial challenge and exercise testing in obese patients with asthma and misdiagnosed asthma compared with obese control subjects to identify the mechanisms of asthma-like symptoms in obesity. In a cross-sectional study we included obese subjects with asthma (n = 25), misdiagnosed asthma (n = 23), and no asthma or respiratory symptoms (n = 27). Spirometry, lung volumes, exhaled nitric oxide levels, and systemic biomarker levels were measured. Dyspnea scores during adenosine bronchial challenge and incremental exercise testing were obtained. During bronchial challenge, patients with asthma or misdiagnosed asthma reached a higher Borg-FEV1 slope than control subjects. Moreover, maximum dyspnea and the Borg-oxygen uptake (V'O2) slope were significantly greater during exercise in subjects with asthma or misdiagnosed asthma than in control subjects. The maximum dyspnea achieved during bronchial challenge correlated with IL-1β levels, whereas peak respiratory frequency, ventilatory equivalent for CO2, and IL-6 and IL-1β levels were independent predictors of the Borg-V'O2 slope during exercise (r(2) = 0.853, P < .001). A false diagnosis of asthma (misdiagnosed asthma) in obese subjects is attributable to an increased perception of dyspnea, which, during exercise, is mainly associated with systemic inflammation and excessive ventilation for metabolic demands.

Obesity and Insulin Resistance Are the Main Determinants of Postprandial Lipoprotein Dysmetabolism in Polycystic Ovary Syndrome.

Postprandial dyslipidaemia may be a plausible mechanism by which polycystic ovary syndrome (PCOS) increases cardiovascular risk. We sought to investigate whether the postprandial glucose and insulin and lipid and lipoprotein responses, including that of apolipoprotein B-48 (apoB-48) containing chylomicrons, to a mixed meal are different in obese PCOS women when compared to obese control subjects and whether differences, if any, are related to obesity, insulin resistance (IR), hyperandrogenaemia, or PCOS status. 26 women with PCOS (age 30.4 ± 1.2 years (mean ± SEM), body mass index (BMI) 36.8 ± 1.5 kg/m2) and 26 non-PCOS subjects (age 34.1 ± 0.9 years, BMI 31.5 ± 1.0 kg/m2) were studied before and up to 8 hours following a standard mixed meal. AUC-triglyceride (AUC-TG) was higher and AUC-high-density lipoprotein (AUC-HDL) lower in PCOS women. These differences were not apparent when BMI was accounted for. Insulin sensitivity (S I), AUC-apoB-48, and AUC-apolipoprotein B (AUC-apoB) were found to be independent predictors of AUC-TG, accounting for 55% of the variance. Only AUC-insulin remained significantly elevated following adjustment for BMI. Obesity related IR explains postprandial hypertriglyceridaemia and hyperinsulinaemic responses. Management of obesity in premenopausal women with PCOS is likely to reduce their cardiovascular risk burden.

Nocturnal Hypoxemia Severity and Renin–Angiotensin System Activity in Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) and nocturnal hypoxemia are associated with chronic kidney disease and up-regulation of the renin-angiotensin system (RAS), which is deleterious to renal function. The extent to which the magnitude of RAS activation is influenced by the severity of nocturnal hypoxemia and comorbid obesity has not been determined. To determine the association between the severity of nocturnal hypoxemia and RAS activity and whether this is independent of obesity in patients with OSA. Effective renal plasma flow (ERPF) response to angiotensin II (AngII) challenge, a marker of renal RAS activity, was measured by paraaminohippurate clearance technique in 31 OSA subjects (respiratory disturbance index, 51 ± 25 h(-1)), stratified according to nocturnal hypoxemia status (mean nocturnal SaO2, ≥90% [moderate hypoxemia] or <90% [severe hypoxemia]) and 13 obese control subjects. Compared with control subjects, OSA subjects demonstrated decreased renovascular sensitivity (ERPF, -153 ± 79 vs. -283 ± 31 ml/min; P = 0.004) (filtration fraction, 5.4 ± 3.8 vs. 7.1 ± 2.6%; P = 0.0025) in response to 60 minutes of AngII challenge (mean ± SD; all P values OSA vs. control). The fall in ERPF in response to AngII was less in patients with severe hypoxemia compared with those with moderate hypoxemia (P = 0.001) and obese control subjects after 30 minutes (P < 0.001) and 60 minutes (P < 0.001) of AngII challenge, reflecting more augmented renal RAS activity. Severity of hypoxemia was not associated with the blood pressure or the systemic circulating RAS component response to AngII. The severity of nocturnal hypoxemia influences the magnitude of renal, but not the systemic, RAS activation independently of obesity in patients with OSA.

Inflammatory metabolites in exhaled breath condensate characterize the obese respiratory phenotype

In humans, obesity plays a critical role in pulmonary inflammation, and is an important risk factor for the development of several inflammatory respiratory diseases. Therefore, understanding the mechanisms that generate mediators in the setting of obesity may help to recognize the link between obesity and chronic respiratory diseases, like the increased incidence and severity of asthma in obese individuals. NMR spectroscopy of exhaled breath condensate (EBC, a non-invasive matrix to access the lung epithelial lining fluid) can unambiguously identify biomarkers characterizing different pulmonary physiopathological states. In this study we aimed at verifying if NMR-based metabolomics of EBC, combined with orthogonal projections to latent structures-discriminant analysis, could possibly recognize specific biomarkers to map the obese metabolic respiratory phenotype. Obese and lean control subjects could be distinguished in a statistical model presenting high quality parameters (R2 = 0.904 and Q2 = 0.871). Identified airway metabolites linked to the inflammation processes demonstrate that obesity constitutes a specific inflammatory metabolic phenotype (metabotype). It is concluded that the noninvasive EBC matrix is suitable to selectively investigate the obesity-related lung inflammation.

Low Serum Vitamin D Levels Are Associated With Increased Arterial Stiffness in Youth With Type 2 Diabetes

OBJECTIVEAdult studies demonstrate that low vitamin D (25[OH]D) is an independent risk factor for arterial stiffness. Similar studies have not been conducted in youth with type 2 diabetes mellitus (T2DM). The objective was to elicit the association between 25[OH]D and arterial stiffness in obese youth with and without T2DM. We hypothesized that 25[OH]D would be inversely correlated with arterial stiffness indices, including pulse wave velocity (PWV), augmentation index (AIx), and brachial distensibility (BrachD).RESEARCH DESIGN AND METHODSCross-sectional analysis was conducted in Cincinnati, OH, from 2004 to 2010. 25[OH]D, PWV, AIx, and BrachD were measured in 190 youth with T2DM, 190 obese control subjects without T2DM, and 190 lean control subjects without T2DM. Multivariate analyses were conducted to elicit the independent association between 25[OH]D and arterial stiffness indices by group.RESULTSThe mean age was 17.9 ± 3.4 years, 55% were African American, and 34% were male. The mean 25[OH]D levels were 21.27, 14.29, and 14.13 ng/mL in lean individuals, obese individuals, and obese individuals with T2DM, respectively (P < 0.01). PWV, AIx, and BrachD worsened from lean to obese to T2DM (P < 0.01). General linear models found that 25[OH]D level was independently associated with PWV in lean individuals and with AIx in the group with T2DM such that a 3 ng/mL increase in 25[OH]D was associated with an AIx decrease of 1% (baseline AIx = 5.7 ± 12.0%).CONCLUSIONS25[OH]D is inversely associated with some measures of arterial stiffness in lean adolescents and obese adolescents with T2DM but not in obese normoglycemic adolescents. Future studies are needed to determine if supplemental 25[OH]D is important for cardiovascular health.

Chitinase 3-like-1 regulates both visceral fat accumulation and asthma-like Th2 inflammation.

Obesity, especially truncal obesity, is a risk factor for asthma incidence, prevalence, and severity. Chitinase 3-like-1 (Chi3l1) is an evolutionarily conserved moiety that plays a critical role in antipathogen and Th2 responses. However, the mechanisms that underlie the association between asthma and obesity and the role(s) of Chi3l1 in fat accumulation have not been defined. To determine whether Chi3l1 is regulated by a high-fat diet (HFD) and simultaneously plays an important role(s) in the pathogenesis of asthma and obesity. We evaluated the regulation of Chi3l1 by an HFD and Th2 inflammation. We also used genetically modified mice to define the roles of Chi3l1 in white adipose tissue (WAT) accumulation and Th2 inflammation and blockers of sirtuin 1 (Sirt1) to define its roles in these responses. Finally, the human relevance of these findings was assessed with a case-control study involving obese and lean control subjects and those with asthma. These studies demonstrate that an HFD and aeroallergen challenge augment the expression of WAT and pulmonary Chi3l1. Chi3l1 also played a critical role in WAT accumulation and lung Th2 inflammation. In addition, Chi3l1 inhibited Sirt1 expression, and the deficient visceral fat and Th2 responses in Chi3l1 null mice were reversed by Sirt1 inhibition. Finally, serum and sputum Chi3l1 were positively associated with truncal adiposity, and serum Chi3l1 was associated with persistent asthma and low lung function in obese subjects with asthma. Chi3l1 is induced by an HFD and Th2 inflammation, and simultaneously contributes to the genesis of obesity and asthma.

"Role of the adipocyte hormone leptin in cardiovascular diseases - a study from Chennai based Population".

BackgroundObesity is currently regarded as a pro-inflammatory condition during which leptin (Ob gene product) might act as a risk factor for Cardiovascular Diseases (CVD) including Acute Myocardial Infarction (AMI). There is a marked increase in circulating leptin concentrations and inflammatory markers such as Tumor Necrosis Factor-α (TNF-α) in AMI patients but still the association of leptin with inflammation during AMI is not known. The present study suggest that elevated levels of leptin might elicit the risk for CVD by signaling for the secretion of inflammatory cytokines especially, TNF-α.MethodsBlood samples were collected from 100 CVD subjects diagnosed for AMI immediately after their admission to the hospital and serum leptin, insulin, glucose, lipids and inflammatory marker such as TNF-α were measured. 5 ml random (non-fasting) blood was collected from 100 non-CVD (control) subjects and the results obtained in case of AMI subjects were compared with that of the control subjects. The subjects under study included both men and women belonging to the age group of 35 – 75 and they were classified based on their BMI as normal weight, overweight and obese.ResultsCirculating levels of leptin are found to be elevated in obese control subjects and in patients with AMI irrespective of their Body Mass Index (BMI). In addition, leptin is also found to be positively correlated to serum triglycerides, insulin and TNF-α in AMI subjects. MANOVA analysis suggests that leptin might influence the synthesis of insulin and TNF-α. This is the first report relating leptin to TNF-α in Chennai based population, India.ConclusionsHyperleptinemia might act as a risk marker for AMI. The present study suggests that at elevated levels, leptin may favor atherosclerosis by promoting the synthesis of TNF-α and insulin. However, our report warrants further investigation both in vitro and in vivo to determine the exact mechanism behind the pro-atherogenic role of leptin. The observed positive correlation between leptin and BMI in both AMI and control subjects suggests that obese subjects manifest leptin resistance and hence, they possess a greater risk for the incidence of CVD.