Mechanisms of endothelial dysfunction in obesity-associated hypertension

Obesity is strongly associated with high blood pressure, dyslipidemia, and type 2 diabetes. These conditions synergistically increase the risk of cardiovascular events. A number of central and peripheral abnormalities can explain the development or maintenance of high blood pressure in obesity. Of great interest is endothelial dysfunction, considered to be a primary risk factor in the development of hypertension. Additional mechanisms also related to endothelial dysfunction have been proposed to mediate the development of hypertension in obese individuals. These include: increase in both peripheral vasoconstriction and renal tubular sodium reabsorption, increased sympathetic activity and overactivation of both the renin-angiotensin system and the endocannabinoid system and insulin resistance. The discovery of new mechanisms regulating metabolic and vascular function and a better understanding of how vascular function can be influenced by these systems would facilitate the development of new therapies for treatment of obesity-associated hypertension.

Prevalence of overweight and obesity in elderly people from Vitória-ES, Brazil

The scope of this study was to estimate the prevalence of overweight and obesity and its association with socio-economic status in a sample of non-institutionalized elderly people from Vitória-ES, Brazil. This was a cross-sectional survey with a sample of 882 elderly people aged 60 and over. Obesity and overweight were assessed using the body mass index (BMI) and waist circumference (WC). All subjects answered a personal and socio-demographic questionnaire in relation to age, gender, marital status, physical activity, number of children, chronic diseases and smoking. Associations between categorical variables were tested using chi-square analysis with a 5% significance level. The prevalence of overweight and obesity was high (41.8% and 23.4%, respectively) and 50.7% of the elderly had a substantially increased waist circumference. About 4.3% of the individuals had diabetes, 50.4% had hypertension and 14.9% were found to have both diseases. It was observed that both the BMI and WC were significant associated (p<0.05) with sex, marital status, the presence of diseases and with cigarette smoking.

Metformin attenuates the exacerbation of the allergic eosinophilic inflammation in high fat-diet-induced obesity in mice

A positive relationship between obesity and asthma has been well documented. The AMP-activated protein kinase (AMPK) activator metformin reverses obesity-associated insulin resistance (IR) and inhibits different types of inflammatory responses. This study aimed to evaluate the effects of metformin on the exacerbation of allergic eosinophilic inflammation in obese mice. Male C57BL6/J mice were fed for 10 weeks with high-fat diet (HFD) to induce obesity. The cell infiltration and inflammatory markers in bronchoalveolar lavage (BAL) fluid and lung tissue were evaluated at 48 h after ovalbumin (OVA) challenge. HFD obese mice displayed peripheral IR that was fully reversed by metformin (300 mg/kg/day, two weeks). OVA-challenge resulted in higher influx of total cell and eosinophils in lung tissue of obese mice compared with lean group. As opposed, the cell number in BAL fluid of obese mice was reduced compared with lean group. Metformin significantly reduced the tissue eosinophil infiltration and prevented the reduction of cell counts in BAL fluid. In obese mice, greater levels of eotaxin, TNF-α and NOx, together with increased iNOS protein expression were observed, all of which were normalized by metformin. In addition, metformin nearly abrogated the binding of NF-κB subunit p65 to the iNOS promoter gene in lung tissue of obese mice. Lower levels of phosphorylated AMPK and its downstream target acetyl CoA carboxylase (ACC) were found in lung tissue of obese mice, which were restored by metformin. In separate experiments, the selective iNOS inhibitor aminoguanidine (20 mg/kg, 3 weeks) and the anti-TNF-α mAb (2 mg/kg) significantly attenuated the aggravation of eosinophilic inflammation in obese mice. In conclusion, metformin inhibits the TNF-α-induced inflammatory signaling and NF-κB-mediated iNOS expression in lung tissue of obese mice. Metformin may be a good pharmacological strategy to control the asthma exacerbation in obese individuals.

Overweight and obesity in relation to socio-economic status, tobacco smoking and plant food supplements usage

Programa de doctorado: Salud Pública (Epidemiología, Planificación y Nutrición)

An interdisciplinary analysis of obesity: theory and empirical evidence

The dissertation is structured in three parts. The first part compares US and EU agricultural policies since the end of WWII. There is not enough evidence for claiming that agricultural support has a negative impact on obesity trends. I discuss the possibility of an exchange in best practices to fight obesity. There are relevant economic, societal and legal differences between the US and the EU. However, partnerships against obesity are welcomed. The second part presents a socio-ecological model of the determinants of obesity. I employ an interdisciplinary model because it captures the simultaneous influence of several variables. Obesity is an interaction of pre-birth, primary and secondary socialization factors. To test the significance of each factor, I use data from the National Longitudinal Survey of Adolescent Health. I compare the average body mass index across different populations. Differences in means are statistically significant. In the last part I use the National Survey of Children Health. I analyze the effect that family characteristics, built environment, cultural norms and individual factors have on the body mass index (BMI). I use Ordered Probit models and I calculate the marginal effects. I use State and ethnicity fixed effects to control for unobserved heterogeneity. I find that southern US States tend have on average a higher probability of being obese. On the ethnicity side, White Americans have a lower BMI respect to Black Americans, Hispanics and American Indians Native Islanders; being Asian is associated with a lower probability of being obese. In neighborhoods where trust level and safety perception are higher, children are less overweight and obese. Similar results are shown for higher level of parental income and education. Breastfeeding has a negative impact. Higher values of measures of behavioral disorders have a positive and significant impact on obesity, as predicted by the theory.

Regulation of wake-sleep states and state-dependent cardiovascular function in diet-induced obesity rats

Obesity often predisposes to coronary heart disease, heart failure, and sudden death. Also, several studies suggest a reciprocal enhancing interaction between obesity and sleep curtailment. Aim of the present study was to go deeper in the understanding of sleep and cardiovascular regulation in an animal model of diet-induced obesity (DIO). According to this, Wake-Sleep (W-S) regulation, and W-S dependent regulation of cardiovascular and metabolic/thermoregulatory function was studied in DIO rats, under normal laboratory conditions and during sleep deprivation and the following recovery period, enhancing either wake or sleep, respectively. After 8 weeks of the delivery of a hypercaloric (HC) diet, treated animals were heavier than those fed a normocaloric (NC) diet (NC: 441 ±17g; HC: 557±17g). HC rats slept more than NC ones during the activity period (Dark) of the normal 12h:12h light-dark (LD) cycle (Wake: 67.3±1.2% and 57.2 ±1.6%; NREM sleep (NREMS): 26.8±1.0% and 34.0±1.4%; REM sleep (REMS): 5.7±0. 6% and 8.6±0.7%; for NC and HC, respectively; p<0.05 for all). HC rats were hypertensive throughout the W-S states, as shown by the mean arterial blood pressure values across the 24-h period (Wake: 90.0±5.3 and 97.3±1.3; NREMS: 85.1±5.5 and 92.2±1.2; REMS: 87.2±4.5 and 96.5±1.1, mmHg for NC and HC, respectively; p<0.05 for all). Also, HC rats appeared to be slightly bradycardic compared to NC ones (Wake: 359.8±9.3 and 352.4±7.7; NREMS: 332.5±10.1 and 328.9±5.4; REMS: 338.5±9.3 and 334.4±5.8; bpm for NC and HC, respectively; p<0.05 for Wake). In HC animals, sleep regulation was not apparently altered during the sleep rebound observed in the recovery period following sleep deprivation, although REMS rebound appeared to be quicker in NC animals. In conclusion, these results indicate that in the rat obesity interfere with W-S and cardiovascular regulation and that DIO rats are suitable for further studies aimed at a better understanding of obesity comorbidities.

Impact of obesity on venous hemodynamics of the lower limbs

Obesity is a risk factor for chronic venous insufficiency and venous thromboembolism. The aim of this study was to compare venous flow parameters of the lower limbs assessed by duplex ultrasound scanning in obese and nonobese individuals according to body mass index (BMI).

Obesity, age, sex, diagnosis, and fixation mode differently affect early cup failure in total hip arthroplasty: a matched case-control study of 4420 patients

Studies about the influence of patient characteristics on mechanical failure of cups in total hip replacement have applied different methodologies and revealed inconclusive results. The fixation mode has rarely been investigated. Therefore, we conducted a detailed analysis of the influence of patient characteristics and fixation mode on cup failure risks.

Overweight and obesity in children: known facts and new trends

The prevalence of overweight and obesity in children is increasing. A growing number of children are thus suffering from complications of obesity. Contributing factors can be found on an individual level as well as in the familial and social environment of affected children. Currently there is no single evidence-based treatment strategy available. Studies from family practice are scarce. Multimodal, long-term, easily accessible treatments as offered in family practice are promising and likely to be cost-effective. The sustainability of these changes in behavior still needs to be demonstrated.

Tackling of unhealthy diets, physical inactivity, and obesity: health effects and cost-effectiveness

The obesity epidemic is spreading to low-income and middle-income countries as a result of new dietary habits and sedentary ways of life, fuelling chronic diseases and premature mortality. In this report we present an assessment of public health strategies designed to tackle behavioural risk factors for chronic diseases that are closely linked with obesity, including aspects of diet and physical inactivity, in Brazil, China, India, Mexico, Russia, and South Africa. England was included for comparative purposes. Several population-based prevention policies can be expected to generate substantial health gains while entirely or largely paying for themselves through future reductions of health-care expenditures. These strategies include health information and communication strategies that improve population awareness about the benefits of healthy eating and physical activity; fiscal measures that increase the price of unhealthy food content or reduce the cost of healthy foods rich in fibre; and regulatory measures that improve nutritional information or restrict the marketing of unhealthy foods to children. A package of measures for the prevention of chronic diseases would deliver substantial health gains, with a very favourable cost-effectiveness profile.

The Influence of Abdominal Pressure on Lower Extremity Venous Pressure and Hemodynamics: A Human In-vivo Model Simulating the Effect of Abdominal Obesity

To demonstrate that abdominal pressure impacts venous flow and pressure characteristics.

Impact of obesity on stroke outcome after intravenous thrombolysis

Obesity is an established risk factor for stroke and has reached epidemic proportions. However, its impact on intravenous thrombolysis applied for acute ischemic stroke is not well known. We aimed to compare the clinical outcome and safety after intravenous thrombolysis in obese (body mass index ≥30 kg/m²) and nonobese (body mass index <30 kg/m²) patients with ischemic stroke.

A multifactorial analysis of obesity as CVD risk factor: use of neural network based methods in a nutrigenetics context

Obesity is a multifactorial trait, which comprises an independent risk factor for cardiovascular disease (CVD). The aim of the current work is to study the complex etiology beneath obesity and identify genetic variations and/or factors related to nutrition that contribute to its variability. To this end, a set of more than 2300 white subjects who participated in a nutrigenetics study was used. For each subject a total of 63 factors describing genetic variants related to CVD (24 in total), gender, and nutrition (38 in total), e.g. average daily intake in calories and cholesterol, were measured. Each subject was categorized according to body mass index (BMI) as normal (BMI ≤ 25) or overweight (BMI > 25). Two artificial neural network (ANN) based methods were designed and used towards the analysis of the available data. These corresponded to i) a multi-layer feed-forward ANN combined with a parameter decreasing method (PDM-ANN), and ii) a multi-layer feed-forward ANN trained by a hybrid method (GA-ANN) which combines genetic algorithms and the popular back-propagation training algorithm.

Burden of abdominal obesity in cardiac rehabilitation patients: Results from the Swiss CaRe study

BACKGROUND: The burden of abdominal obesity (AO) and its association with other cardiovascular risk factors is not known in coronary artery disease (CAD) patients attending cardiac rehabilitation (CR). The aim of this study was, therefore, to investigate the prevalence of AO and differences in cardiovascular risk factors between AO and non-AO patients. METHODS: 415 consecutive male CAD patients (mean age 58 ± 11 years) attending a three-month outpatient CR programme were assessed. Differences in cardiovascular risk profile, including blood lipids, psychosocial and socioeconomic status and exercise capacity, were compared in relation to AO and corrected for obesity measured by body-mass index (BMI) in a multivariate analysis. RESULTS: Mean waist circumference was 102 ± 11 cm. Patients of lower educational level had a higher prevalence of AO (p = 0.021) than patients with a higher educational level. AO was significantly associated with diabetes (p = 0.003) and hypertension (p <0.001). In AO patients, HDL-C levels were lower (p <0.001) and triglyceride levels higher (p = 0.006) than in non-AO patients. There was no difference in exercise capacity between AO and non-AO patients, but AO patients had a higher resting heart rate (p = 0.021). CONCLUSION: AO is highly prevalent in CAD patients attending CR. AO is, independently of BMI, associated with metabolic lipid disorders and autonomic cardiovascular dysregulation, suggesting an increased cardiovascular risk. AO patients therefore need particular attention during CR and follow-up care.