The Association of Resistance Exercise With the Inflammasome Activation in Obesity Subjects

Study Overview
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Brief Summary
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The intervention study consist in 3 months of follow up to evaluate the effect of resistance exercise on NLRP3 and interleukin-18 (IL-18) gene expression, and IL-18 and IL-1b cytokines levels in obese subjects, due to, the current evidence has been suggested that aerobic physical exercise could reduce the low-grade chronic inflammation through the downregulation of the NLRP3 inflammasome in obesity subjects, however, there are not enough evidence with resistance protocol. The investigator randomized into two intervention groups: a) group with resistance exercise training plus hypocaloric diet, and b) group with hypocaloric diet. The blood sample was taken fasting at baseline and final intervention (3rd month). The serum was separated for biochemical analyzes and the quantification of cytokines levels. The RNA was obtained from leukocytes to expression assay.

Detailed Description
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Obesity is a metabolic condition with a high worldwide prevalence. It is characterized by low-grade chronic inflammation and high cytokines level as consequence of the excessive accumulation of adipose tissue. The NLRP3 protein is part of the NLRP3 inflammasome, a multiprotein complex related to inflammation and the risk of developing metabolic disorders. In this sense, the evidence has been suggested that physical exercise could reduce the inflammation through the downregulation of the NLRP3 inflammasome. The aim of this study is evaluate the effect of resistance exercise on NLRP3 and IL-18 gene expression and and IL-18 and IL-1b cytokines levels in obese subjects. This is an experimental study with 3 months of follow up. Participants were randomized into two intervention groups: a) group with resistance exercise plus hypocaloric diet, and b) group with hypocaloric diet. The exercise program was design by certified personal trained, and consisted in 3 phases: conditioning, development and maintenance. Dietary information was collect by validated retrospective questionnaires (24-hour record and 3-days dietary diary) and analyzed in Nutritionist Pro software. Body composition was evaluated by bioimpedance. The biochemical analyzes were performed on serum sample using spectrophotometry equipment. RNA was obtained from leukocytes from peripheral blood, cDNA synthesis was performed with a ThermoFisher kit, and the expression assay was performed by real-time polymerase chain reaction (PCR) using Taqman probes with the 2-ΔΔcq relative quantification method. Cytokines quantification were perform using a commercial ELISA kit. Statistical analysis will be using the Statistical Package for Social Sciences (SPSS v.25) software and a value of p<0.05 will be considered statistically significant.

Official Title
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The Potential Role of Resistance Exercise on Inflammasome Activation and Cytokines Levels in Obese Subjects

Conditions
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Physical Activity, Resistance Exercise, Inflammation, Obesity

Intervention / Treatment
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* Behavioral: Resistance exercise training plus hypocaloric diet
* Behavioral: Hypocaloric diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Both sex Older than 25 years old Women with waist circumference ≥ 80cm and men with ≥ 90cm Subjects with BMI between 30 and 40 kg/m2 Exclusion Criteria: Subjects with diagnosis of metabolic alterations Subjects with chronic pharmacological treatment Subjects with anti-inflammatories drugs prescription

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Experimental
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Resistance exercise training plus hypocaloric diet<br>The participants received a caloric restriction of 20% of total energy estimated with Mifflin formula plus a structured, planned, and controlled resistance exercise program by a personal trained. The participant received the exercise program instructions every week and they performed by the own, and record the heart rate of each session on a paper format. All the appointment were once a month by trained nutritionists, and all the participants received a nutritional recommendation for the obesity management and a balanced food plan. | Behavioral: Resistance exercise training plus hypocaloric diet<br>* The exercise program included 3 phases of progressive intervention: 1) Adaptation which included 3-4 days per week at 60% of maximum heart rate, 2) Development phase which included 5 days per week at 75-85% of maximum heart rate and the last one, 3) Maintenance phase which included 5 days per week at 75-90% of maximum heart rate. The control and follow up will be through text message exchanges at least once a week or as many as necessary. On the other hand, the diet intervention consisted a caloric restriction of 20% of total energy estimated with Mifflin formula. The nutrients distributions are 50% for carbohydrates, 20% for protein and 30% for lipids, ensuring a sufficient intake of fiber (>25g per day).<br>|
| Active Comparator: Hypocaloric diet<br>The participants received a caloric restriction of 20% of total energy estimated with Mifflin formula. All the appointment were once a month by trained nutritionists, and all the subjects received a nutritional recommendation for the obesity management and a balanced food plan. | Behavioral: Hypocaloric diet<br>* The diet intervention consisted a caloric restriction of 20% of total energy estimated with Mifflin formula. The nutrients distributions are 50% for carbohydrates, 20% for protein and 30% for lipids, ensuring a sufficient intake of fiber (>25g per day).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NLRP3 gene expression | Assay expression will be performed by real-time PCR using Taqman probes with the 2-ΔΔcq relative quantification method | Change from baseline NLRP3 gene expression at 3 months | 
| IL-18 gene expression | Assay expression will be performed by real-time PCR using Taqman probes with the 2-ΔΔcq relative quantification method | Change from baseline IL-18 gene expression at 3 months | 
| IL-18 cytokine | commercial ELISA kit | Change from baseline IL-18 cytokine at 3 months | 
| IL-1b cytokine | commercial ELISA kit | Change from baseline IL-1b cytokine at 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight | Weighing machine using bioimpedance technology | Change from baseline weight at 3 months | 
| Body fat mass | Weighing machine using bioimpedance technology | Change from baseline body fat mass at 3 months | 
| Serum triglycerides | Liquid chemistry using spectrum equipment | Change from baseline serum triglycerides at 3 months | 
| Serum cholesterol | Liquid chemistry using spectrum equipment | Change from baseline serum cholesterol at 3 months | 
| Serum glucose | Liquid chemistry using spectrum equipment | Change from baseline serum glucose at 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Resistance training, inflammasome, Obesity