Clinical trial NCT05490862: Inflammatory Status of Monocytes in Obesity
Official title: Inflammatory Status of Monocytes in Obesity: Association With Atherosclerosis Indicators and the Effectiveness of Weight Loss
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Obesity
Cardiovascular Diseases
Keywords: obesity
Cardiovascular risk factors
atherosclerosis
Inflammation
Monocytes
Cytokines
Lead sponsor: Federal State Budgetary Scientific Institution "Federal Research Centre of Nutrition, Biotechnology
Sponsor class: OTHER
Collaborators: name: Petrovsky National Research Centre of Surgery
First posted: 2022-08-08
Enrollment: 100
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Match pairs Parallel group Double-control design
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Changes of pro-inflammatory macrophages activation
timeFrame: Twice: Baseline, treatment week 12
measure: Mitochondrial genome mutations
timeFrame: One time measurement (baseline)
Secondary outcomes:
measure: Changes of body mass
timeFrame: Twice: Baseline, treatment week 12
measure: Changes of body fat mass
timeFrame: Twice: Baseline, treatment week 12
measure: Changes of skeletal muscle mass
timeFrame: Twice: Baseline, treatment week 12
measure: Changes of Serum Cholesterol levels
timeFrame: Twice: Baseline, treatment week 12
measure: Framingham Risk Score
timeFrame: Twice: Baseline, treatment week 12
measure: Intima-media thickness
timeFrame: One time measurement (baseline)
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Department of Cardiovascular Pathology and Diet
Study officials:
affiliation: Federal State Budgetary Scientific Institution "Federal Research Centre of Nutrition, Biotechnology
name: Yurgita R Varaeva, MD, MRes
role: PRINCIPAL_INVESTIGATOR
References: