Inflammatory Status of Monocytes in Obesity

Inflammatory Status of Monocytes in Obesity: Association With Atherosclerosis Indicators and the Effectiveness of Weight Loss

The study of the pro-inflammatory activation of circulating monocytes/macrophages in obesity is the main problem of this project. The investigation of pro-inflammatory activation of monocytes and determination of the level of mitochondrial genome mutations, assessment of traditional CVD risk factors and the degree of cardiovascular risk and atherosclerosis indicators and their association will be investigated in dynamics on 12-weeks weight loss.

Obesity is one of the main risk factors for cardiovascular disease (CVD), which occupy the first place in the overall structure of mortality in developed countries, and therefore it is a serious medical and social problem and an urgent research topic in modern science. Inflammation is one of the key factors in the development of cardiovascular complications of obesity, in particular atherogenesis. Currently, the mechanisms of inflammation in obesity are widely studied, in experimental studies, special attention is paid to the study of macrophages of adipose tissue, their inflammatory activation and their role in the development of obesity-associated pathological conditions. Circulating monocytes in dense tissue differentiate into macrophages and play an important role in the pathogenesis of chronic inflammation. Increased pro-inflammatory activation of macrophages in the focus of inflammation can cause chronic inflammation and contribute to the development of atherosclerotic lesions in the vascular wall. Mitochondrial dysfunction may play a special role in the proinflammatory activation of monocytes since it leads to the accumulation of oxygen radicals and activates the excessive secretion of inflammatory mediators. Mitochondrial genome mutations are one of the possible mechanisms leading to the development of mitochondrial dysfunction. Previously, atherosclerosis-associated mutations of the mitochondrial genome were identified, however, in obesity, the level of mitochondrial heteroplasmy has not been studied. Weight loss is associated with a decrease in cardiovascular risk; however, the mechanisms of the cardioprotective effects of weight loss are not fully understood. The anti-inflammatory effects of vigorous exercise in obesity are being actively studied. The study of the pro-inflammatory activation of circulating monocytes/macrophages in obesity is the main problem of this project. The following tasks will be solved within the framework of the project: 1. Investigation of pro-inflammatory activation of monocytes and determination of the level of mitochondrial genome mutations in obese individuals. 2. Comprehensive assessment of the association of monocyte activation, mitochondrial genome mutations and traditional CVD risk factors and the degree of cardiovascular risk and atherosclerosis indicators in obese individuals. 3. Study on the effect of weight loss after a 3-month course of body weight loss, consisting of a set of physical exercises in combination with a low-calorie diet on the inflammatory status of monocytes in obese individuals. As a result of the project, data on the inflammatory status of monocytes in obesity will be obtained and published, the effect of pro-inflammatory activation of monocytes, mitochondrial genome mutations in combination with traditional CVD risk factors on indicators of atherosclerosis and cardiovascular risk in obese individuals will be investigated. Data on the effect of a weight loss intervention (a combination of exercise complex and low-calorie diet) on the inflammatory status of monocytes will be obtained and published. The study of cellular markers of inflammation and the identification of mitochondrial genome mutations in obese individuals will deepen the understanding of the mechanisms of chronic inflammation in obesity and obesity-associated cardiovascular complications. The study of the effect of weight loss on the inflammatory status of monocytes - key cells in the development of chronic inflammation - may become a promising direction for the development of approaches for personalized pathogenetic therapy of obesity and prevention of obesity-associated cardiovascular complications.

Low-calorie diet and regular physical trainings will be administered to obese participants (BMI >30kg/m^2).

An individualized low-calorie diet is characterized by sugars and starchy food intake restriction, 500 kcal daily energy deficit for 12 weeks (3 months). Regular physical activity is represented by individualized 30 minutes trainings on an anti-gravity treadmill 3 workouts per week for 12 weeks with individual targets of stepping activity, which will be evaluated according to personal fitness monitoring data

The measurement of basal and lipopolysaccharide-induced tumor necrosis factor-α and interleukin-1β levels in the culture of cluster differentiation 14+ cells obtained from participants blood samples

The assessment of mtDNA mutation heteroplasmy m.652delG, m.1555A>G, m.3336T>C, m.3256C>T, m.5178C>A, m.12315G>A, m.13513G>A, m.14459G>A , m.14846G>A и m.15059G>A by real-time polymerase chain reaction

Includes repeated assessment of body fat mass (%) by bio-impedancemetry body composition analysis and calculation of fat mass loss.

Includes repeated assessment of skeletal muscle mass (%) by bio-impedancemetry body composition analysis and calculation of muscle mass changes (positivo or negative).

The measurement of serum total cholesterol and cholesterol sbgroups levels by standard laboratory procedures. The decrease of cholesterol levels is considereed as positeve effect.

The assessment of estimated 10-year cardiovascular risk (%) according to the Framingham Risk Score that varies from less than 10% (low risk) to more than 20% (high risk). The reduction od risk will be considered as positive effect of intervention.

The assessment of intima-media thickness of common carotid artery evaluated by B-mode ultrasound imagining.

Obese Weight Loss and Control groups Inclusion Criteria: • BMI ≥30 kg/m2 Lean Control group Inclusion Criteria: • BMI <25 kg/m2 Exclusion Criteria: Diabetes Mellitus Cancer Uncontrolled Hypertension Decompensated liver or kidney disease III-IV classes of Chronic Heart Failure Other chronic diseases (except CVDs) on permanent treatment.