Obesity Cardiovascular Disease Research Articles

Cardiac biogenic amine profile and its relationship with parameters of cardiovascular disease in obesity

AimsTo identify the cardiac biogenic amine profile of obese rats and associate these compounds with parameters of cardiovascular disease. Main methodsWistar rats (n = 20) were randomly distributed into two groups: control and obese. Obesity was induced by a high-sugar fat diet. Biochemical parameters were evaluated. Doppler Echocardiography and systolic blood pressure; interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), protein carbonylation, ferric reducing antioxidant power (FRAP), and catalase activity were measured in cardiac tissue. HPLC evaluated the cardiac biogenic profile. Data were compared using the Student's T or Mann-Whitney tests and Spearman's correlation at 5% significance. The principal component analysis (PCA) was performed. Key findingsObesity generated hypertension, cardiac remodeling and dysfunction, and imbalanced all biochemical, inflammatory, and oxidative markers (p < 0.001). Eight biogenic amines were found in cardiac tissue. Obesity increased serotonin and decreased agmatine, putrescine, cadaverine, and spermidine. Serotonin (r = 0.534 to 0.808) was strong and positively correlated with obesity, biochemical parameters, cardiac inflammation, oxidative stress, hypertension, cardiac remodeling, and dysfunction (p < 0.001). Spermidine (r = −0.560 to −0.680), putrescine (r = −0.532 to −0.805), cadaverine (r = −0.534 to −0.860), and agmatine (r = −0.579 to −0.884) were inversely correlated with the same parameters (p < 0.001). PCA allowed for distinguishing the control and obese groups. SignificanceThere are strong correlations between cardiac biogenic amine levels, cardiac remodeling, and dysfunction resulting from obesity. ConclusionThere is an association between cardiac biogenic amines and cardiovascular disease in obesity. In addition, agmatine, putrescine, cadaverine, and, mainly, serotonin may be new biomarkers for cardiovascular health in obesity and help to improve the diagnosis and treatment of CVD resulting or not from obesity. However, more research is needed to support this conclusion.

The Pathophysiological Associations Between Obesity, NAFLD, and Atherosclerotic Cardiovascular Diseases.

Obesity, non-alcoholic fatty liver disease (NAFLD), and atherosclerotic cardiovascular diseases are common and growing public health concerns. Previous epidemiological studies unfolded the robust correlation between obesity, NAFLD, and atherosclerotic cardiovascular diseases. Obesity is a well-known risk factor for NAFLD, and both of them can markedly increase the odds of atherosclerotic cardiovascular diseases. On the other hand, significant weight loss achieved by lifestyle modification, bariatric surgery, or medications, such as semaglutide, can concomitantly improve NAFLD and atherosclerotic cardiovascular diseases. Therefore, certain pathophysiological links are involved in the development of NAFLD in obesity, and atherosclerotic cardiovascular diseases in obesity and NAFLD. Moreover, recent studies indicated that simultaneously targeting several mechanisms by tirzepatide and retatrutide leads to greater weight loss and markedly improves the complications of metabolic syndrome. These findings remind the importance of a mechanistic viewpoint for breaking the association between obesity, NAFLD, and atherosclerotic cardiovascular diseases. In this review article, we mainly focus on shared pathophysiological mechanisms, including insulin resistance, dyslipidemia, GLP1 signaling, inflammation, oxidative stress, mitochondrial dysfunction, gut dysbiosis, renin-angiotensin-aldosterone system (RAAS) overactivity, and endothelial dysfunction. Most of these pathophysiological alterations are primarily initiated by obesity. The development of NAFLD further exacerbates these molecular and cellular alterations, leading to atherosclerotic cardiovascular disease development or progression as the final manifestation of molecular perturbation. A better insight into these mechanisms makes it feasible to develop new multi-target approaches to simultaneously unhinge the deleterious chain of events linking obesity and NAFLD to atherosclerotic cardiovascular diseases.

PO-03-092 MACHINE LEARNING ANALYSIS OF THE PREDICTORS OF AF RECURRENCE POST-ABLATION IN PATIENTS UNDERGOING PRE-ABLATION MRI

Catheter ablation, a widely performed rhythm control strategy for atrial fibrillation (AF), has variable results in the complete suppression of arrhythmia recurrence, especially in obese patients. Structural remodeling of the left atrium (LA), evidenced by LA enlargement and fibrosis, is a well-known substrate for AF. Epicardial adipose tissue (EAT) is thought to be a crucial factor mediating cardiovascular disease in obesity, it can result in electrical heterogeneity and local conduction block forming a substrate for AF. We aimed to apply a machine learning approach to assess the predictors of AF recurrence following catheter ablation in AF patients undergoing pre-ablation cardiac magnetic resonance (CMR). 101 AF patients underwent CMR prior to catheter ablation. Fibrotic remodeling was assessed using the late gadolinium enhancement sequence. EAT was assessed using the novel fat-water separation 3D Dixon sequence. Panel A shows posterior and anterior views of a representative LA model showing fibrotic remodeling and EAT. Patients were followed for AF recurrence using ambulatory monitoring and 12-lead ECGs. A random forest classifier with 5x stratified cross-validation was trained to predict AF recurrence post-ablation and SHapley Additive exPlanations (SHAP) analysis was used to assess feature importance in the prediction of AF recurrence. During an average follow-up period of 1 year, post-ablation AF recurrence occurred in 31 (30.7%) patients. Patients with AF recurrence post-ablation had higher LA EAT index (20.7 [16.9, 30.4] vs 13.7 [10.5, 20.1] mL/m2, p<0.001), and higher LA volume index (66 [52.6, 77.5] vs 49.9 [37.7, 61.8] mL/m2, p=0.001). There was a trend toward a higher fibrosis burden in patients who had an AF recurrence (18.6% vs 16.1%, p=0.076). The classifier predicted AF recurrence post-ablation with an AUC of 0.67 ± 0.09 (Panel B). SHAP analysis revealed that for the overall population, the three most important features in the prediction of AF recurrence post-ablation were LA volume index, LA EAT index, and LA fibrosis (Panel C). LA enlargement, fibrosis and EAT, markers with clear ties to AF pathophysiology, are predictors of AF recurrence after ablation. Future studies testing the value of an imaging-based ablation failure prediction calculator, as well as studies to elucidate the mechanism of ablation failure, are required.

The frequency of metabolically healthy and unhealthy phenotypes in women aged 25–44 years with different levels of thyroid-stimulating hormone, prolactin, leptin

Reports that the risk of developing cardiovascular diseases in obesity is not the same, led to the allocation of metabolically healthy and unhealthy phenotypes (MHP and MUHP), this concept is based on the ability of adipose tissue to produce a number of adipokines, one of which is leptin. Hormones such as thyroid-stimulating hormone (TSH) and prolactin (PRL) are interesting from the point of view of their effect on metabolism. Aim of the study was to investigate the prevalence of MHP and MUHP in young women with different body mass index (BMI) and hormonal status (TSH, PRL, leptin) in different phenotypes. Material and methods. A group of women (n = 655) was selected from a representative sample of the Novosibirsk population aged 25–44 to study clinical and laboratory parameters. The design is a cross – sectional, observational, single – centre study. IDF, 2005 and NCEP ATP III, 2001 criteria were used to evaluate the MHP and MUHP. Results and discussion. The prevalence of MUHP in young women in Novosibirsk was 22.3 %, MHP – 77.7 % according to IDF, 2005; according to NCEP ATP III, 2001 – 13.1 and 86.9 %, respectively. The prevalence of MUHP increased with increasing BMI from 4.0 to 72.0 % according to IDF, 2005 and from 2.3 to 58.0 % according to NCEP ATP III, 2001, respectively. In obese women, MUHP was detected twice as often as MHP – 72 and 28 % according to IDF, 2005, 58 and 42 % according to NCEP ATP III, 2001. TSH and PRL do not provide information about metabolic health in young women. Leptin content is associated with BMI. The threshold value of the leptin level was 18.3 ng/ml with maximum sensitivity and specificity (Se = 53.3 %, Sp = 81.5 %), 14.5 ng/ml with equal sensitivity and specificity (Se = 65.7 %, Sp = 65.7 %). The area under ROC curve (AUC) for diagnosis of MUHP was 0.727 (SE = 0.029, p &lt; 0.0001). Conclusion. The frequency of MHP in young women decreases with increasing BMI. MUHP is 3.5 times less common than MHP according to IDF criteria, 2005. TSH and PRL are not associated with the metabolic phenotype in young women. A leptin level more than 18.3 ng/ml has been identified as one of the markers for the recognition of MUHP in women aged 25–44 years, regardless of BMI.

Biomarkers of Oxidative Stress Tethered to Cardiovascular Diseases.

Cardiovascular disease (CVD) is a broad term that incorporated a group of conditions that affect the blood vessels and the heart. CVD is a foremost cause of fatalities around the world. Multiple pathophysiological mechanisms are involved in CVD; however, oxidative stress plays a vital role in generating reactive oxygen species (ROS). Oxidative stress occurs when the concentration of oxidants exceeds the potency of antioxidants within the body while producing reactive nitrogen species (RNS). ROS generated by oxidative stress disrupts cell signaling, DNA damage, lipids, and proteins, thereby resulting in inflammation and apoptosis. Mitochondria is the primary source of ROS production within cells. Increased ROS production reduces nitric oxide (NO) bioavailability, which elevates vasoconstriction within the arteries and contributes to the development of hypertension. ROS production has also been linked to the development of atherosclerotic plaque. Antioxidants can decrease oxidative stress in the body; however, various therapeutic drugs have been designed to treat oxidative stress damage due to CVD. The present review provides a detailed narrative of the oxidative stress and ROS generation with a primary focus on the oxidative stress biomarker and its association with CVD. We have also discussed the complex relationship between inflammation and endothelial dysfunction in CVD as well as oxidative stress-induced obesity in CVD. Finally, we discussed the role of antioxidants in reducing oxidative stress in CVD.

ACUTE PANCREATITIS IN CHILDREN AND MULTISYSTEMIC INFLAMMATORY SYNDROME POST COVID INFECTION 19

During the SARSCoV2 pandemic children appear less likely to develop severe form Compared to adult subjects with higher contagiousness and mortality, especially in those at risk (age over 65 obesity cardiovascular disease diabetes). However a new multisystemic inflammatory syndrome associated with SARSCoV2 has been identified in the child associated with a cascade of inflammatory response responsible for clinical symptoms (prolonged high fever digestive disorders rash cheilite conjunctivit) and a highly disturbed inflammatory biological profile (high CRP accelerated sedimentation rate hyperferritinemia) mimicking an atypical post covid 19 Kawasaki syndrome in children as was recently published in the literature. Our case will illustrate an unusual presentation of post covid 19 multisystemic inflammatory Syndrome acute pancreatitis in a 9-year old with favorable clinical and biological development.

Obesity Duration, Severity, and Distribution Trajectories and Cardiovascular Disease Risk in the Atherosclerosis Risk in Communities Study.

BackgroundResearch examining the role of obesity in cardiovascular disease (CVD) often fails to adequately consider heterogeneity in obesity severity, distribution, and duration.Methods and ResultsWe here use multivariate latent class mixed models in the biracial Atherosclerosis Risk in Communities study (N=14 514; mean age=54 years; 55% female) to associate obesity subclasses (derived from body mass index, waist circumference, self‐reported weight at age 25, tricep skinfold, and calf circumference across up to four triennial visits) with total mortality, incident CVD, and CVD risk factors. We identified four obesity subclasses, summarized by their body mass index and waist circumference slope as decline (4.1%), stable/slow decline (67.8%), moderate increase (24.6%), and rapid increase (3.6%) subclasses. Compared with participants in the stable/slow decline subclass, the decline subclass was associated with elevated mortality (hazard ratio [HR] 1.45, 95% CI 1.31, 1.60, P<0.0001) and with heart failure (HR 1.41, 95% CI 1.22, 1.63, P<0.0001), stroke (HR 1.53, 95% CI 1.22, 1.92, P=0.0002), and coronary heart disease (HR 1.36, 95% CI 1.14, 1.63, P=0.0008), adjusting for baseline body mass index and CVD risk factor profile. The moderate increase latent class was not associated with any significant differences in CVD risk as compared to the stable/slow decline latent class and was associated with a lower overall risk of mortality (HR 0.85, 95% CI 0.80, 0.90, P<0.0001), despite higher body mass index at baseline. The rapid increase latent class was associated with a higher risk of heart failure versus the stable/slow decline latent class (HR 1.34, 95% CI 1.10, 1.62, P=0.004).ConclusionsConsideration of heterogeneity and longitudinal changes in obesity measures is needed in clinical care for a more precision‐oriented view of CVD risk.

Cardiovascular Diseases in Obesity: What is the Role of Magnesium?

An excess of adipose tissue, a characteristic of obesity, has been associated with endocrine-metabolic alterations that contribute to dyslipidemias, which are characterized by an increase in the plasma concentrations of triacylglycerols, total cholesterol, and LDL-c along with a reduction in HDL-c. Some nutrients such as the mineral magnesium play important roles in lipid metabolism. Magnesium regulates the activity of HMG-CoA reductase, increasing the activity of lipoprotein lipase and lecithin-cholesterol acyltransferase. The objective of this review is to present important aspects about the contribution of obesity to the manifestation of cardiovascular risk, to bring the main physiological functions of magnesium, as well as the role of the nutrient in the protection against cardiovascular diseases. Studies have shown that individuals with obesity have low intracellular concentrations of magnesium, which can compromise the nutrient's physiological functions. Thus, this mineral appears to play an important role in protecting against cardiovascular diseases; however, changes in the nutrient metabolism in obesity may compromise the functions of this element. Further studies are needed to clarify this.

Prevention of Diabetes and Cardiovascular Disease in Obesity.

Obesity is one of the major risk factors for the development of both impaired glucose tolerance (IGT, or prediabetes) and type 2 diabetes (T2D), and its prevalence worldwide drives toward an increased rate of cardiovascular morbidity and mortality. Given the estimations of the World Health Organization (WHO) and the recommendation of the Diabetes Prevention Program (DPP), where IGT and diabetes are considered as risk factors for the development of cardiovascular complications and obesity, the development of diabetes should be treated because of its potential reversibility. In this view, several interventions such as diet, lifestyle changes, and pharmacological treatment are effective, including bariatric metabolic surgery (BMS), which is the most incisive way to efficiently lower body weight. In this review, we sought to summarize some of the major aspects linked to diabetes prevention in overweight/obesity, focusing on the use of surgery; we also attempted to elucidate molecular pathways involved in a variety of obesity-induced processes able to favor the progression of chronic diseases, such as diabetes and its complications.

Is the Retinol-Binding Protein 4 a Possible Risk Factor for Cardiovascular Diseases in Obesity?

Although many preventive and treatment approaches have been proposed, cardiovascular disease (CVD) remains one of the leading causes of deaths worldwide. Current epidemiological data require the specification of new causative factors, as well as the development of improved diagnostic tools to provide better cardiovascular management. Excessive accumulation of adipose tissue among patients suffering from obesity not only constitutes one of the main risk factors of CVD development but also alters adipokines. Increased attention is devoted to bioactive adipokines, which are also produced by the adipose tissue. The retinol-binding protein 4 (RBP4) has been associated with numerous CVDs and is presumably associated with an increased cardiovascular risk. With this in mind, exploring the role of RBP4, particularly among patients with obesity, could be a promising direction and could lead to better CVD prevention and management in this patient group. In our review, we summarized the current knowledge about RBP4 and its association with essential aspects of cardiovascular disease—lipid profile, intima-media thickness, atherosclerotic process, and diet. We also discussed the RBP4 gene polymorphisms essential from a cardiovascular perspective.

Non-Systematic Review of Diet and Nutritional Risk Factors of Cardiovascular Disease in Obesity.

Although cardiovascular disease and its risk factors have been widely studied and new methods of diagnosis and treatment have been developed and implemented, the morbidity and mortality levels are still rising—cardiovascular disease is responsible for more than four million deaths each year in Europe alone. Even though nutrition is classified as one of the main and changeable risk factors, the quality of the diet in the majority of people does not follow the recommendations essential for prevention of obesity and cardiovascular disease. It demonstrates the need for better nutritional education in cardiovascular disease prevention and treatment, and the need to emphasize dietary components most relevant in cardiovascular disease. In our non-systematic review, we summarize the most recent knowledge about nutritional risk and prevention in cardiovascular disease and obesity.

Endothelial Dysfunction in Obesity-Induced Inflammation: Molecular Mechanisms and Clinical Implications.

Obesity is characterized by the excessive deposition of fat that may interfere with the normal metabolic process of the body. It is a chronic condition associated with various metabolic syndromes, whose prevalence is grossly increasing, and affects both children and adults. Accumulation of excessive macronutrients on the adipose tissues promotes the secretion and release of inflammatory mediators, including interleukin-6 (IL-6), interleukin 1β, tumor necrotic factor-α (TNF-α), leptin, and stimulation of monocyte chemoattractant protein-1 (MCP-1), which subsequently reduce the production of adiponectin thereby initiating a proinflammatory state. During obesity, adipose tissue synthesizes and releases a large number of hormones and cytokines that alter the metabolic processes, with a profound influence on endothelial dysfunction, a situation associated with the formation of atherosclerotic plaque. Endothelial cells respond to inflammation and stimulation of MCP-1, which is described as the activation of adhesion molecules leading to proliferation and transmigration of leukocytes, which facilitates their increase in atherogenic and thromboembolic potentials. Endothelial dysfunction forms the cornerstone of this discussion, as it has been considered as the initiator in the progression of cardiovascular diseases in obesity. Overexpression of proinflammatory cytokines with subsequent reduction of anti-inflammatory markers in obesity, is considered to be the link between obesity-induced inflammation and endothelial dysfunction. Inhibition of inflammatory mechanisms and management and control of obesity can assist in reducing the risks associated with cardiovascular complications.

2162Neurofibromin 2 (NF2) drives obesity-related endothelial dysfunction by targeting Caveolin-1: a study in mice and humans

Abstract Introduction Endothelial dysfunction (ED) is a key underpinning of cardiovascular disease in obesity, but the underlying molecular mechanisms remain elusive. Neurofibromin 2 (NF2) is a scaffold-like protein implicated in various cellular processes, namely growth, differentiation and survival. NF2 is inactivated by Akt-dependent phosphorylation at Ser518, whereas its dephosphorylation by the myosin phosphatase target subunit 1 (MYPT-1) leads to an active conformation. The role of NF2 in obesity-related alterations of endothelial phenotype remains elusive. Purpose To investigate whether NF2 participates to ED in obesity. Methods Human aortic endothelial cells (HAECs) were exposed to palmitic acid (PA, 200 uM) or vehicle for 48 hours. Gene silencing of NF2 was performed by small interfering RNA (siRNA). Protein expression was assessed by Western blot. Nitric oxide (NO) levels were measured by using a colorimetric assay. The interaction of NF2 with endothelial proteins was investigated by co-immunoprecipitation. To specifically determine NF2 role in the endothelium, we generated mice with endothelium-specific deletion of NF2 (NF2 ECKO) by crossing NF2flox/flox mice with tamoxifen-inducible endothelial-specific cre mice [Cdh5(PAC)-CreERT2]. Endothelium-dependent relaxations to acetylcholine (Ach, 10–9 to 10–5 mol/L) were assessed in aortas isolated from male NF2 ECKO and wild type littermates, fed a control (10 kcal% fat) and a high fat diet (60 kcal% fat) for 20 weeks. NF2 signalling and endothelial function were also assessed in small visceral fat arteries (VFA) isolated from 18 obese and 18 age-matched healthy subjects undergoing bariatric surgery and cholecystectomy, respectively. Results Exposure of HAECs to PA decreased NF2 phosphorylation at Ser518, thus leading to an active protein conformation. Blunted NF2 phosphorylation was explained by a reduction of Akt phosphorylation at Ser473 and a concomitant increase of MYPT-1 phosphorylation at Thr696. Pull-down experiments revealed that NF2 binds and activates Caveolin 1 (Cav-1), a pivotal repressor of endothelial NO synthase (eNOS). NF2 knockdown in PA-treated HAECs prevented eNOS–Cav-1 interaction, thus preserving eNOS activity and NO levels. In aortas from obese mice, we found that NF2-Cav-1 interaction was responsible for impaired eNOS activity, reduced NO levels and endothelial dysfunction. By contrast, Ach-dependent vasorelaxation were preserved in obese mice with endothelium-specific deletion of NF2. Moreover, we found that NF2 is activated in VFA from obese patients as compared to healthy controls, and its activity negatively correlated with Ach-dependent vasorelaxation of isolated VFA, as assessed by organ chamber experiments. Conclusions The present findings – obtained in human endothelial cells, conditional mouse models and visceral fat arteries from obese patients – suggest that targeting NF2 may represent a potential therapeutic strategy to prevent ED in patients with obesity.

SAT-253 Association between TSH and Cardiovascular Risk Parameters in Obese Children and Adolescents

Introduction: Hyperthyrotropinemia is common in overweight and obese patients and has been hypothesized that high TSH, even within the normal limits, could be associated with an adverse metabolic profile. Objective: Aim of the study was to evaluate the association between TSH and cardiovascular risk parameters in a large group of obese children and adolescents. Patients and Methods: 1402 obese patients (median age 9.7 (2.2-17.8) y, 646 boys) were included in this retrospective analysis. All patients were euthyroid or had mild isolated hyperthyrotropinemia with TSH <10 µU/ml and normal fT4. Waist circumference (WC), systolic and diastolic blood pressure (SP and DP), fasting glycemia, insulin and lipids were measured in all subjects. An Oral Glucose Tolerance Test (OGTT) was also performed (glucose load of 1.75 g/kg of ideal body weight, max 75 g). Insulin resistance was evaluated by Homeostatic Model Assessment (HOMA index, glycemia (mmol/L) x insulin (mU/L) / 22.5). Patients were subdivided into 3 groups according to their TSH level: normal-low TSH (group A, 930 patients, TSH: ≥0,5 - <2.5 µU/ml), normal-high TSH (group B, 432 patients, TSH: ≥2,5 - <4.5µU/ml), mild isolated hyperthyrotropinemia (group C, 40 patients, TSH: ≥4.5 - <10 µU/ml). Results: Median BMI, WC, and fT4 were similar between the 3 groups. The prevalence of patients with high SP, hypertension (high SP and/or DP), and abnormal LDL was higher in patients with hyperthyrotropinemia versus euthyroid patients (p≤0.01), but no differences were found between normal-low and normal-high TSH patients (abnormal SP prevalence: group A 12.6%, group B 14.7%, group C 30.1%; hypertension: group A 14.3%, group B 18.1%, group C 36.1%; abnormal LDL prevalence: group A 14.6%, group B 16.3%, group C 37.5%). Median insulin and HOMA and the prevalence of patients with abnormal HOMA were higher in group C (17 mU/ml, 3,87, and 65%, respectively) than in group A (12.4 mU/ml, 2.64, 39,6%, p≤0.007), and were higher in group B (14 mU/ml, 3,07, 49%, respectively) than in group A (p≤0.001). DP, basal and post-OGTT glycemia, total cholesterol, HDL and triglycerides were not different between the three groups. Conclusions: In our large cohort of obese children and adolescents, increasing TSH was associated with hypertension, insulin resistance and increased LDL, regardless of BMI and fT4 level. These results confirm that TSH, even if in the normal range, could be associated with an adverse metabolic profile. Further studies are needed to define if TSH could be involved in the pathogenesis of cardiovascular diseases in obesity.

Sympathetic nervous system as a target for aging and obesity-related cardiovascular diseases.

Chronic sympathetic nervous system overactivity is a hallmark of aging and obesity and contributes to the development of cardiovascular diseases including hypertension and heart failure. The cause of this chronic sympathoexcitation in aging and obesity is multifactorial and centrally mediated. In this mini-review, we have provided an overview of the key and emerging central mechanisms contributing to the pathogenesis of sympathoexcitation in obesity and healthy aging, specifically focusing on hypertension. A clear understanding of these mechanisms will pave way for targeting the sympathetic nervous system for the treatment of cardiovascular diseases in obesity and aging.

Leptin and Aldosterone.

The prominence of obesity in the clinical population as well as the strong association of cardiovascular risk factors with obesity has prompted the investigation of the adipose tissue and its physiological contribution to cardiovascular health. A notable finding in these investigations was the discovery of the adipocyte-derived hormone leptin. Leptin is secreted from the adipose tissue, increases in linear fashion in the circulation with increased body mass and is implicated in the development of cardiovascular disease in obesity, notably via pro-hypertensive mechanisms. Leptin stimulates the activation of the sympathetic nervous system in male patients and mice, which has been implicated as the pro-hypertensive pathway for leptin in obesity. However, obese premenopausal females do not exhibit increased sympathetic activation in response to hyperleptinemia in obesity, indicating a sex-discrepancy in mechanisms of obesity-associated hypertension. Our lab recently demonstrated that leptin also induces the adrenal production of aldosterone in a direct fashion and that this pathway leads to the hyperaldosteronemia that is characteristic of obesity. We have also published data that indicate that the implications of leptin-induced aldosterone are of particular impact in obese females. Leptin-mediated hypertension and endothelial dysfunction, a significant predictor of hypertension clinically, require activation of the mineralocorticoid receptor in female mice. The clinical potential of this pathway remains under investigation; however, existing data indicate that a sex discrepancy exists in mechanisms of leptin-mediated hypertension between males and females and that leptin-stimulated aldosterone plays a significant role in females.

Relationship among obesity, blood lipids and insulin resistance in Bangladeshi adults

IntroductionInsulin resistance (IR) and abnormal lipid profiles are the risk factors for cardiovascular diseases in obesity. To clarify the relationship of the changes in insulin resistance, body weight and lipid profile, the present study was performed on Bangladeshi adults, total of 1500 individuals at the time of their general health examination in the hospital. MethodsAfter exclusion of other endocrine diseases, the remaining 772 patients were classified as IR ≥ 2 and IR < 2 based on the homeostatic model assessment-estimated insulin resistance (HOMA-IR) index. The endocrine disease free subjects were further clustered based on age, gender and obesity. The anthropometric and biochemical profiles were statistically analyzed and correlated with IR ≥ 2 and IR<2 groups as well as other clusters of the subjects. Apart from some disparities, notable differences were observed in all anthropometric data. ResultsTotal cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and serum insulin levels were significantly higher in IR ≥ 2 group in comparison with IR<2 group. Obesity and dyslipidemia were associated as prevalent components of IR. Generalized linear model revealed that TC: LDL and TG: HDL had significant effect on IR. Age group II (41–60 years old) subjects had significantly higher lipid profile compared to age group I (20–40 years old) and age group III (61–80 years old). ConclusionsResults reported herein support the notion that lipoprotein ratios might be the reliable biomarkers to evaluate IR.

Relationship among Obesity, Blood Lipids and Insulin Resistance in Bangladeshi Adults

Introduction: Insulin resistance (IR) and abnormal lipid profiles are the risk factors for cardiovascular diseases in obesity. To clarify the relationship of the changes in insulin resistance, body weight and lipid profile, the present study was performed on Bangladeshi adults, total of 1500 individuals at the time of their general health examination in the hospital.Methods: After exclusion of other endocrine diseases, the remaining 772 patients were classified as IR ≥ 2 and IR<2 based on the homeostatic model assessment-estimated insulin resistance (HOMA-IR) index. The endocrine disease free subjects were further clustered based on age, gender and obesity. The anthropometric and biochemical profiles were statistically analyzed and correlated with IR ≥ 2 and IR˂2 groups as well as other clusters of the subjects. Apart from some disparities, notable differences were observed in all anthropometric data.Results: Total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and serum insulin levels were significantly higher in IR ≥ 2 group in comparison with IR˂2 group. Obesity and dyslipidemia were associated as prevalent components of IR. Generalized linear model revealed that TC: LDL and TG: HDL had significant effect on IR. Age group II (41-60 years old) subjects had significantly higher lipid profile compared to age group I (20-40 years old) and age group III (61-80 years old).Conclusions: Results reported herein support the notion that lipoprotein ratios might be the reliable biomarkers to evaluate IR.

The role of leptin signalling in the development of cardiovascular diseases in obesity

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Does fitness improve the cardiovascular risk profile in obese subjects?

Background and aimsGood cardiorespiratory fitness has been suggested to reduce the risk of cardiovascular disease in obesity. We explored the association of fitness with the prevalences of major cardiovascular risk factor like hypertension (HT), diabetes and metabolic syndrome (MetS) in overweight and obese subjects. Methods and resultsClinical data from 491 participants in the FAT associated CardiOvasculaR dysfunction (FATCOR) study were analyzed. Physical fitness was assessed by ergospirometry, and subjects with at least good level of performance for age and sex were classified as fit. HT subtypes were identified from clinic and 24-h ambulatory blood pressure in combination. Diabetes was diagnosed by oral glucose tolerance test. MetS was defined by the American Heart Association and National Heart, Lung and Blood Institute criteria. The participants were on average 48 years old (60% women), and mean body mass index (BMI) was 32 kg/m2. 28% of study participants were classified as fit. Fitness was not associated with lower prevalences of HT or HT subtypes, diabetes, MetS or individual MetS components (all p > 0.05). In multivariable regression analysis, being fit was characterized by lower waist circumference, BMI < 30 kg/m2, non-smoking and a higher muscle mass (all p < 0.05). ConclusionIn the FATCOR population, fitness was not associated with a lower prevalence of major cardiovascular risk factors like HT, diabetes or MetS. Given the strong association of cardiovascular risk factor burden with risk of clinical cardiovascular disease, these findings challenge the notion that fitness alone is associated with lower risk of cardiovascular disease in obesity.