Clinical trial NCT05482178: The Association of Resistance Exercise With the Inflammasome Activation in Obesity Subjects
Official title: The Potential Role of Resistance Exercise on Inflammasome Activation and Cytokines Levels in Obese Subjects
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Physical Activity
Resistance Exercise
Inflammation
Obesity
Keywords: Resistance training
inflammasome
Obesity
Lead sponsor: Universidad Autónoma de Sinaloa
Sponsor class: OTHER
First posted: 2022-08-01
Enrollment: 20
Sex: ALL
Minimum age (years): 25
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Experimental
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: NLRP3 gene expression
timeFrame: Change from baseline NLRP3 gene expression at 3 months
measure: IL-18 gene expression
timeFrame: Change from baseline IL-18 gene expression at 3 months
measure: IL-18 cytokine
timeFrame: Change from baseline IL-18 cytokine at 3 months
measure: IL-1b cytokine
timeFrame: Change from baseline IL-1b cytokine at 3 months
Secondary outcomes:
measure: Weight
timeFrame: Change from baseline weight at 3 months
measure: Body fat mass
timeFrame: Change from baseline body fat mass at 3 months
measure: Serum triglycerides
timeFrame: Change from baseline serum triglycerides at 3 months
measure: Serum cholesterol
timeFrame: Change from baseline serum cholesterol at 3 months
measure: Serum glucose
timeFrame: Change from baseline serum glucose at 3 months
Other outcomes:
Locations:
city: Culiacán
country: Mexico
facility: Autonomous University of Sinaloa
state: Sinaloa
Study officials:
affiliation: Autonomous University of Sinaloa
name: Elisa Barron, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Metsios GS, Moe RH, Kitas GD. Exercise and inflammation. Best Pract Res Clin Rheumatol. 2020 Apr;34(2):101504. doi: 10.1016/j.berh.2020.101504. Epub 2020 Apr 2.
citation: Izaola O, de Luis D, Sajoux I, Domingo JC, Vidal M. [Inflammation and obesity (lipoinflammation)]. Nutr Hosp. 2015 Jun 1;31(6):2352-8. doi: 10.3305/nh.2015.31.6.8829. Spanish.
citation: Ozaki E, Campbell M, Doyle SL. Targeting the NLRP3 inflammasome in chronic inflammatory diseases: current perspectives. J Inflamm Res. 2015 Jan 16;8:15-27. doi: 10.2147/JIR.S51250. eCollection 2015.
citation: You T, Berman DM, Ryan AS, Nicklas BJ. Effects of hypocaloric diet and exercise training on inflammation and adipocyte lipolysis in obese postmenopausal women. J Clin Endocrinol Metab. 2004 Apr;89(4):1739-46. doi: 10.1210/jc.2003-031310.
citation: Barron-Cabrera E, Gonzalez-Becerra K, Rosales-Chavez G, Mora-Jimenez A, Hernandez-Canaveral I, Martinez-Lopez E. Low-grade chronic inflammation is attenuated by exercise training in obese adults through down-regulation of ASC gene in peripheral blood: a pilot study. Genes Nutr. 2020 Aug 27;15(1):15. doi: 10.1186/s12263-020-00674-0.
citation: Butts B, Butler J, Dunbar SB, Corwin E, Gary RA. Effects of Exercise on ASC Methylation and IL-1 Cytokines in Heart Failure. Med Sci Sports Exerc. 2018 Sep;50(9):1757-1766. doi: 10.1249/MSS.0000000000001641.
citation: Nakajima K, Takeoka M, Mori M, Hashimoto S, Sakurai A, Nose H, Higuchi K, Itano N, Shiohara M, Oh T, Taniguchi S. Exercise effects on methylation of ASC gene. Int J Sports Med. 2010 Sep;31(9):671-5. doi: 10.1055/s-0029-1246140. Epub 2010 Mar 3.