Effects of combined training on interleukin-7 plasma levels in obese middle-aged men

Efeitos do treinamento combinado sobre as concentrações plasmáticas de interleucina-7 em homens obesos de meia-idade

ABSTRACT

Introduction:  There are divergences about the effects of obesity on plasma concentrations of inter-leukin-7 (IL-7) and the role of physical exercise as a metabolic regulator of this cytokine.

Objective:  To compare the plasma concentrations of IL-7 between obese and normal weight individuals, in addition to evaluating the effects of combined training (CT) on concentrations of this cytokine in obese individuals.

Methods:  Initially, obese group (OG, n = 15) and normal weight group (NWG, n = 8) were compared. Subsequently, the obese individuals participated in a pre-post 16-week exper-imental period and were randomly distributed into obese CT group (OT, n = 8) and obese control group (OC, n = 7). Physical fitness, body composition, and IL-7 concentrations evaluations were performed. The CT program consisted of strength training and aerobic training in the same session.

Results:  A significant increase of IL-7 was observed in the OG (27.14 ± 3.64 pg/mL) compared to the NWG (21.26 ± 3.93 pg/mL) (p = 0.01). Although no significant group x time interaction was found, a time effect was observed in the pre-post experimental period on IL-7 concentrations (OC: 18.8%, ES: 1.68; OT: 28.5%, ES: 5.15). In the assessment of the effect size, a greater reduction in OT was observed. Moreover, reductions in weight, body mass index and fat mass were observed in the OT group when compared to CG, accompanied by significant increases in 1 maximum repeti-tion test in the Leg Press and Bench Press, and maximum oxygen consumption.

Conclusion:  Obese individuals have higher circulating concentrations of IL-7, which suggest that elevated body weight and fat are associated with an increase in this cytokine. Although the effect size for IL-7 was larger in the OT group, probabilistic statistics did not show a significant effect.

Keywords:
Combined training; Physical exercise; Interleukin-7; Obesity; Inflammation; Metabolism.

RESUMO

Introdução:  Existem divergências sobre os efeitos da obesidade nas concentrações plasmáticas de interleucina-7 (IL-7) e do papel do exercício físico como regulador metabólico dessa citocina.

Objetivo:  Comparar as concentra-ções plasmáticas de IL-7 entre indivíduos obesos e com peso normal, além de avaliar os efeitos do treinamento combinado (TC) nas concentrações dessa citocina em indivíduos obesos.

Métodos:  Inicialmente, foram compara-dos o grupo obeso (GO, n = 15) e o grupo com peso normal (GNT, n = 8). Posteriormente, os indivíduos obesos participaram de um período experimental de 16 semanas e foram distribuídos aleatoriamente em grupo TC obeso (OT, n = 8) e grupo controle obeso (OC, n = 7). Foram realizadas avaliações de aptidão física, composição corporal e concentrações de IL-7. O programa de TC consistiu em treinamento de força e treinamento aeróbico na mesma sessão.

Resultados:  Um aumento significativo de IL-7 foi observado no GO em comparação ao GNT (p = 0,01). Embora não tenha sido encontrada interação grupo x tempo significativa, foi observado efeito de tempo no período pré-pós experimental sobre as concetrações de IL-7 (OC: 18,8%, ES: 1,68; OT: 28,5%, ES: 5,15). A avaliação do tamanho do efeito, indicou uma maior redução no OT. Além disso, reduções no peso, índice de massa corporal e massa gorda (kg) foram observadas no grupo OT quando comparado ao GC, acompanhadas por aumentos significativos em no teste de uma repetição máxima no Leg Press e no Supino, e no consumo máximo de oxigênio.

Conclusão:  Indivíduos obesos apresentam maiores concentrações circulantes de IL-7, o que sugere que o aumento do peso corporal e da gordura corporal está associado a um aumento dessa citocina. Embora o tamanho do efeito para IL-7 tenha sido maior no grupo OT, a estatística probabilística não mostrou um efeito significativo.

Palavras-chave
Treinamento combinado; Exercício físico; Interleucina-7; Obesidade; Inflamação; Me-tabolismo

Introduction

Obesity is considered a global pandemic that compromises quality of life and can lead to morbidity and mortality¹. Excess body fat, especially in the visceral region and in ectopic compartments, generates a pro-cess of low-grade chronic inflammation². These factors contribute to the increase in the concentration of cir-culating cytokines and other inflammatory markers, which can develop to diseases such as type 2 diabetes, atherosclerosis, hypertension, and cancers³.

Among the various inflammatory markers, interleu-kin-7 (IL-7) has been gaining prominence for its pleio-tropic effects, because despite to being associated with inflammatory induction, it also presents important an-ti-inflammatory and regulatory effects such as growth, survival, maturation, and development of T cells⁴,⁵.

In studies about obesity, discrepant results have been found in the relationship between plasma IL-7 values and gene expression in adipocytes. While some studies have demonstrated an increase in circulating IL-7 in pre-diabetic obese women⁶ and in gene ex-pression in adipocytes of obese men⁷. Other findings verified the relationship between excess body fat and thymic involution and impaired maturation and conse-quent reduction of T cells, a process in which IL-7 has a significant role⁷,⁸. This divergence of results becomes especially significant after acute administration of ex-ogenous IL-7 was able to prevent the accumulation of body fat, reduce markers associated with inflammation, and protect against glucose intolerance in a model of mice obese by a high-fat diet⁹, showing its therapeutic potential in the management of metabolic complica-tions related to obesity. However, possible differences in circulating IL-7 concentrations in obese men with-out diabetes and other comorbidities compared to nor-mal weight individuals are not well known.

Physical exercise has been shown to be an important anti-inflammatory agent and is considered a non-pharmacological treatment for obesity¹⁰,¹¹. Specif-ically, muscle contraction performed in an acute ses-sion of physical exercise has been shown to promote the survival of naïve T cells¹², as well as increasing cir-culating concentrations of IL-7 in elderly athletes who practice cycling when compared to sedentary elderly people¹³. Additionally, an increase in IL-7 gene expres-sion was observed in the skeletal muscle of obese rats subjected to a combined training (CT) protocol (with the resistance and aerobic exercises in the same train-ing session), which is recommended for the mainte-nance and improvement of health¹⁴. However, it is im-portant to highlight the differences in effects between animal and human models, especially in the context of the time for which effects can be observed. Additional-ly, although there is evidence that physical exercise can interfere with IL-7 secretion¹³, exploration in this context focuses more on acute effects in humans , which raises doubts about the effects of chronic training and its influence on serum levels, especially in a population with excess body fat.

Based on the divergence in circulating concentra-tions of IL-7 according to body weight, and how phys-ical training can interfere in this context, the present study aims to compare the plasma concentrations of IL-7 between obese and normal weight individuals, in addition to evaluating the effects of CT applied to obese individuals on the concentrations of this cyto-kine through a randomized and controlled study.

Methods

Subjects and experimental design

This paper presents the results of IL-7 dosages from the research project “Investigation of the effects of combined training on early immunosenescence asso-ciated with obesity,” which aims to evaluate the re-sponses of CT on cardiovascular, neuromuscular, body composition, biochemical, and molecular variables in obese individuals. The study was approved by the Re-search Ethics Committee of Universidade Estadual de Campinas (CAAE: 16563719.7.0000.5404; Approval number 6.017.319) according to the principles of the Declaration of Helsinki. The volunteers were informed of the purpose of the study and signed the informed consent form.

The inclusion criteria adopted were: men and women in middle age (40 to 60 years) classified as grade 1 obese (body mass index [BMI] between 30.0-35.0 kg/m²) or normal weight (BMI between 18.5-25.0 kg/ m²); have a non-active lifestyle; have not regularly par-ticipated in training programs or undergone any type of systematic diet over the last 12 months prior to the beginning of the experiment. Particularly in the case of women, the volunteers should be in menopause. The exclusion criteria were: volunteers who demonstrated in the anamnesis, or in the clinical evaluation (gener-al physical, cardiological and ergometric examination) and/or laboratory tests any disease (coronary artery disease, severe arterial hypertension, chronic obstruc-tive pulmonary disease, limiting osteoarticular diseases, type 1 and 2 diabetes) that could affect research results or indicate a risk factor or unwillingness to participate in the proposed physical activities; or those who were taking any medication that could affect their physical responses to the tests or exercise, such as anti-inflam-matories; and not having IL-7 data evaluated.

The following discontinuation criteria were also ad-opted: a) the volunteer’s lack of motivation or unavail-ability to attend the training sessions and/or tests; b) attendance at training sessions of less than 85% and/ or more than three consecutive absences; c) other risks to the volunteers that could occur even after clinical clearance.

Volunteers were instructed not to change their medications if used (dosage/types) or their eating pat-tern during the experimental period. The control group was not submitted to any training protocol and was followed up on monthly by telephone during the ex-perimental period.

Before the study, all subjects (normal weight group - NWG and obese group - OG) carried out an assess-ment of physical activity levels, anthropometry, body composition, food intake, physical fitness analyses (muscular maximal strength and maximum cardiore-spiratory capacity), and blood collection for plasma IL-7 analysis. After the experimental period, obese subjects were randomized into the obese control (OC) and obese training (OT) groups and repeated the ini-tial assessments (except physical activity levels anal-yses evaluated only in pre moment). In the 8^th week of training, the OT participants performed another cardiorespiratory test to readjust the aerobic training loads. Each assessment was performed in a room with an average temperature of 23°C, with the volunteers breathing spontaneously in atmospheric air. The volun-teers were familiarized with the location, procedures, tests, and equipment used before the study.

Physical activity questionnaire

The Baecke questionnaire was applied to assess the level of physical activity of the subjects. This is a self-report instrument used to measure an individual’s habitual physical activity over the past 12 months. In the period prior to the study, none of the selected volunteers per-formed systematic physical exercises or sports, and did not engage in significant physical activity in the context of leisure and occupational activities. Thus, all subjects were categorized as sedentary/irregularly active¹⁰.

Nutritional assessment

Food intake was monitored before and after the exper-imental period through food records. Volunteers were asked to list all foods and beverages they consumed during the designated days (two non-consecutive weekdays and one weekend day). Total caloric intake, quantity/proportions of macronutrients (carbohydrates, lipids, and proteins) were calculated based on the aver-age of the data from the three FRs, using the Diet Pro Program, Diet Pro, version 5i, Dietpro Store (Viçosa, Minas Gerais, Brazil).

Anthropometry and body composition

To calculate BMI (kg/m²), a scale (FilizolaTM, São Pau-lo, Brazil) was used to obtain body mass data, and a wood-en stadiometer (0.1 cm accuracy) to measure height. The BMI was calculated from these measurements.

To assess body composition data, a whole-body plethysmography system (air displacement plethys-mography (BOD POD - Cosmed, Inc., Concord, United States) was used. The assessment was made according to the criteria discussed in the equipment manual and the criteria normally used in this assess-ment. After determining body density by plethysmog-raphy, body composition was measured from these data based on the Siri equation¹⁵.

Maximum muscle strength and cardiorespiratory assessment

To determine the maximum muscular strength of the upper and lower limbs, the one-repetition maximum (1-RM) test was used in the leg press and bench press exercises. Subjects were required to perform 10 repe-titions at 50% of 1RM estimated (according to each participant’s capacity). After 3 min of rest, subjects were required to perform 3 repetitions at 70% of 1RM estimated. Another 3 min of rest was applied, and then subsequent trials were performed for 1RM with progressively heavier weights until the 1RM was de-termined within three attempts, with 3-5 min of rest between trials. All subjects were tested at baseline by two separate sessions (test-retest) with 48-h rest be-tween them. To determine the results of the 1RM tests at baseline, we used the value of the highest load ob-tained after the test-retest¹⁰.

The cardiorespiratory assessment was performed by performing an effort protocol on a treadmill (Quinton, model TM55, Seattle, United States), with continu-ous collection of expired gases with each breath (CPX Ultima, Medgraphics, Saint Paul, United States). The protocol had an initial warm-up speed of 4 km/h for 2 minutes, with increases of 0.3 km/h every 30 seconds, and a constant incline of 1% until physical exhaustion. Then there was a 4-minute recovery, with the first min-ute at 5 km/h, decreasing by 1 km/h every minute¹⁰. A Polar® interface recorded heart rate during the execu-tion of this protocol and the subjective perception of effort scale (Borg scale) was applied every minute. The average data from the last 30 seconds of the test, ven-tilation, maximum oxygen consumption (VO₂max.), and speed of physical exhaustion were used to assess cardiorespiratory fitness¹⁰,¹⁶.

Blood collection and biochemical analysis

Blood samples (~20 ml) were collected of the antecu-bital vein in vacuum tubes with anticoagulant (EDTA). The collections were made between 7:00 and 10:00 a.m. All volunteers were instructed: not to perform any activities before collection for 72 hours; fasting for 12 hours; and not to consume alcohol or caffeine 24 hours before collection.

Subsequently, the collected blood samples were subjected to the centrifugation process to separate the blood plasma, which was stored in a freezer at -80° C for later analysis.

Plasma IL-7 concentrations were determined in duplicate using the ELISA (Enzyme-Linked Immu-nosorbent Assay) method, adhering to the recommen-dations and specifications of the high-sensitivity kits (Quantikine HS ELISA kits, Catalog No. HS750, R&D Systems, Minneapolis, United States). The kits have a sensitivity of 0.1 pg/mL and an intraand in-terassay coefficient of variation of 3.3% and 7.8%, re-spectively.

Combined training

Strength training (ST) and aerobic training (AT) were performed in the same session by OT. These training sessions were divided into two stages and performed on 3 alternating days throughout the week (Mondays, Wednesdays, and Fridays). During stage 1, partici-pants performed ST through a linear periodization with knee flexion, knee extension, 45º leg press, high pulldown, barbell curl, bench press, shoulder press, and triceps pulley, performed in all sessions; and calf exten-sion/flexion and upper abdominal exercises performed in one or two sessions per week, with an alternation of these two exercises per session. Strength exercises were performed in 3 sets of 10-12 submaximal repeti-tions (without apparent Valsalva maneuver, apnea, and concentric failure) with a one-minute interval between sets, taking approximately 35 minutes to complete the session. Evaluating the training load in the bench press and leg press with the results of the 1RM test of these exercises, the load was between 65 to 80% of 1RM. During this phase, the ordering of the exercises was alternated by segment. Subsequently, participants performed 36 minutes of walking/running on the treadmill. The AT had variation in intensity, such as: 4 minutes between 50 and 55% of VO₂max; 14 minutes between 55 and 65% of VO₂max; 14 minutes between 65-75% of VO₂max; and 4 minutes between 50 and 55% of VO₂max¹⁴.

In stage 2, ST was maintained as in E1, however, with a decrease in volume and an increase in intensi-ty, being 8-10 submaximal repetitions (70 to 80% of 1RM) and a 1 minute and 15-second rest between sets. Following the same duration of E1 per session. During this phase, the exercises were organized by perform-ing the largest muscle groups and then the smallest. For AT, there was no change in training volume, only a progressive increase in intensity that followed the pat-terns of 4 minutes between 55 and 60% of VO₂max; 14 minutes at 60 and 70% of VO₂max; 14 minutes at 70 and 80% of VO₂max; and 4 minutes between 55 and 60% of VO₂max¹⁴.

To control the intensity of AT, the calculation/ transformation of VO2max values was used as a basis for the heart rate and speed established on the tread-mill. In addition, maximum repetition tests were per-formed in the last session of each week to adjust the ST according to previously adopted procedures¹⁰,¹¹.

Statistical analysis

The Kolmogorov-Smirnov test was applied to identify data normality. To verify possible differences between OG and NWG, the independent Student’s t-test was used. To compare pre-experimental period values and delta percentage change (∆%) of OT and OC the in-dependent Student’s t-test, also was applied.

To compare pre-and post-experimental period ef-fects (OC and OT groups), analysis of variance (ANO-VA) for repeated measures was applied to determine significant differences between time*groups/treatment, followed by Tukey’s post hoc (when applicable).

Pearson’s correlation coefficient tests were per-formed to evaluate the correlation of plasma IL-7 (baseline NWG and OG, and ∆% of OT group) with anthropometric, body composition, physical fitness, and nutritional variables. Finally, we also calculated the “d” effect size for IL-7 (in cross-sectional and experimental period). Data are presented as mean ± standard devia-tion, and the significance level used was p ≤ 0.05. All analyses were performed using Statistica 6.0 software.

Results

Cross-sectional results (NWG vs. OG)

A total of 23 volunteers completed the cross-sectional study. In the baseline comparison, 8 subjects composed the NWG; (2 women and 6 men), and 15 the OG (4 women and 11 men).

The characterization and comparison data of NWG and OG are presented in Tables 1 and Figure 1. The NWG shows lower weight, BMI, fat mass (kg and %), lean mass (kg), and lipid intake. The NWG also pres-ents a higher protein consumption and lean mass per-centage when compared to the OG (Table 1).

Table 1
Characterization of the groups at the pre-intervention stage

Variable	Normal weight group (n = 8)	Obese group (n = 15)	p value
Age (years)	52.25 ± 4.20	51.66 ± 4.35	0.75
Weight (kg)	67.81 ± 8.51	94.80 ± 14.32 *	< 0.001
Height (meters)	1.70 ± 0.06	1.69 ± 0.12	0.91
Body mass index (m/kg2)	23.38 ± 1.53	32.85 ± 1.62 *	< 0.001
Carbohydrate intake (g/day)	45.46 ± 2.07	42.99 ± 6.51	0.38
Lipid intake (g/day)	27.97 ± 4.06	35.42 ± 4.54 *	< 0.001
Protein intake (g/day)	26.56 ± 4.14	21.51 ± 5.54 *	0.05
Total calorie intake (kcal/day)	1669.24 ± 333.97	1760.87 ± 539.18	0.66
1 Repetition Maximum Leg Press (kg)	191.25 ± 36.42	226.00 ± 58.92	0.14
1 Repetition Maximum Bench Press (kg)	31.00 ± 12.56	35.83 ± 12.30	0.38
Maximum oxygen consumption (ml/kg/min)	30.50 ± 4.70	25.77 ± 5.20 *	0.04
Lean mass (kg)	51.72 ± 8.19	59.02 ± 10.67 *	< 0.01
Lean mass (%)	74.82 ± 6.93	62.37 ± 6.01 *	< 0.001
Fat mass (kg)	17.28 ± 4.84	35.39 ± 7.42 *	< 0.001
Fat mass (%)	25.17 ± 6.93	37.68 ± 5.90*	< 0.001

• Normal weight Group n = 8. Obese Group n = 15. Values presented as Mean ± Standard deviation.
• ^*
  = p ≤ 0.05

Figure 1
Comparison of plasma interleukin-7 between normal weight and obese groups

Regarding the plasma concentrations of IL-7 be-tween the NWG and OG, higher levels were observed in IL-7 levels of obese (NWG = 21.26 ± 3.93 pg/mL; OG = 27.14 ± 3.64 pg/mL; p = 0.01) (Figure 1). The effect size of this difference between groups was ES = 1.54, which shows a large magnitude of difference between the groups.

Experimental períod results - Obese Combined Training Group (OT) vs. Obese Group (OG)

After baseline comparisons, the OG was divided for the experimental period into an OT (n = 8; 2 women and 6 men) and an OC (n = 7; 2 women and 5 men).

The pre and post-clinical data of the OT and OC groups are presented in Table 2 and Figure 2. The OT group presented an increase in 1RM Leg Press (Tukey p< 0.001), 1 RM Bench Press (Tukey p< 0.001), and VO₂max (Tukey p< 0.02). The OT also showed a ten-dency to decrease weight (Tukey p = 0.07) and BMI (Tukey p = 0.06). When comparing the ∆% of OC and OT, differences were observed in weight (OC = 0.73% vs. OT = -2.22%, p = 0.02), BMI (OC = 0.73% vs. OT = -2.22%, p = 0.02), fat mass (OC = -0.68% vs. OT = -11.10%, p = 0.04), 1RM leg press (OC = 6.67% vs. OT = 37.88%, p = 0.001), 1 RM bench press (OC = 1.43% vs. OT = 35.17%, p = 0.0001) and VO₂ (OC = -11.76% vs. OT = 16.07%, p = 0.0001).

Table 2
Pre and post values of anthropometric variables, body composition, physical fitness and eating behavior of the obese control and training groups

training groups
Variable	Obese Training Group (n = 8) Pre Post		∆%	Obese Control Group (n = 7) Pre Post		∆%	ANOVA group* time
Age (years) Height (meters) Weight (kg)	51.94 ± 2.84 1.69 ± 0.08 98.12 ± 16.33	- - 95.90 ± 16.01	- - -2.2 ± 2.7 &	52.00 ± 4.93 1.67 ± 0.12 91.01 ± 11.65	- - 91.60 ± 11.09	- - 0.7 ± 1.3	- - 0.03
Body mass index (m/kg2)	33.14 ± 1.67	32.40 ± 1.78	-2.2 ± 2.7 &	32.53 ± 1.62	32.76 ± 1.59	0.7 ± 1.3	0.02
Carbohydrate intake (g/day)	43.79 ± 7.35	46.03 ± 10.79	4.8 ± 4.8	42.06 ± 6.60	47.68 ± 7.27	7.4 ± 15.8	0.80
Lipid intake (g/day)	35.13 ± 5.07	34.88 ± 8.06	-0.2 ± 19.8	35.90 ± 4.79	31.25 ± 5.11	-12.4 ± 14.9	0.35
Protein intake (g/day)	21.06 ± 5.97	19.07 ± 4.38	-6.5 ± 18.1	22.04 ± 6.17	21.05 ± 6.00	-8.6 ± 44.1	0.78
Total calorie intake (kcal/day)	1720.00 ± 656.83	1776.76 ± 513.89	6.9 ± 18.0	1808.66 ± 467.63	1731.72 ± 288.21	-5.8 ± 18.2	0.29
1 Repetition maximum Leg Press (kg)	223.75 ± 46.88	306.87 ± 61.92 *	37.9 ± 15.6 &	228.57 ± 74.31	243.57 ± 86.92	6.7 ± 15.0	0.001
1 Repetition maximum Bench Press (kg)	35.10 ± 12.97	47.70 ± 16.84*	35.2 ± 18.0 &	36.78 ± 12.44	37.42 ± 13.61	1.4 ± 7.9	0.001
Maximum oxygen consumption (ml/kg/min)	25.34 ± 4.17	29.04 ± 2.90*	16.1 ± 12.0 &	26.27 ± 6.50	22.67 ± 4.24	-11.8 ± 11.9	< 0.001
Lean mass (kg)	59.32 ± 10.82	61.38 ± 11.82	3.5 ± 9.2	58.67 ± 11.36	58.92 ± 11.09	0.5 ± 3.6	0.42
Lean mass (%)	60.71 ± 6.81	64.07 ± 10.02	5.4 ± 9.3	64.27 ± 4.72	64.45 ± 5.10	0.3 ± 2.3	0.20
Fat mass (kg)	38.42 ± 9.23	34.58 ± 11.61	-11.1 ± 17.4&	31.93 ± 1.76	31.75 ± 2.76	-0.7 ± 3.6	0.10
Fat mass (%)	39.26 ± 6.81	35.78 ± 9.99	-9.5 ± 17.6	35.87 ± 4.48	35.54 ± 5.10	-1.0 ± 4.6	0.13

• Values presented as Mean ± Standard deviation.
• ^*
  p ≤ 0.05 in the comparison between the pre and post moments by the Tukey post hoc.

Figure 2
Behavior of plasma interleukin-7 in the pre and post-experimental period of the obese control group and obese training group groups A- Pre-post results. B- ∆% results. OT: Obese training group n = 8. OC: Obese control group n = 7. Values presented as Mean ± Standard deviation.

The plasma concentrations of IL-7 in the preand post-intervention moments of the OT and OC groups are shown in Figure 2-A. Although no significant group x time interaction was found in the ANOVA (p = 0.67), a time effect was observed in the pre-post experimental period on IL-7 concentrations (OC = pre 25.95 ± 4.45, post 20.52 ± 1.02 pg/mL; OT= pre 27.41 ± 1.93, post 19.90 ± 0.72 pg/mL; p< 0.0001). In the effect size of the pre-post values of each group, the OT presents an ES = 5.15 and the OC an ES = 1.68. No significant differences were observed between the ∆% of the groups (OC = -18.82% vs OT = -28.50%, p = 0.12) (Figure 2-B). In the effect size of the percentage deltas, an ES = 0.77 was observed, which is considered a medium/large magnitude of difference.

Regarding the analysis of correlations in premo-ment with all subjects together, a positive correlation was found between IL-7 with body weight (r = 0.66; p = 0.01; figure 3-A), BMI (r = 0.65; p = 0.01; figure 3-B), and fat mass (r = 0.48; p = 0.03; figure 3-C). No significant correlations were observed between the ∆% of the OT.

Figure 3
Significant correlation.

Discussion

The main findings show that obese individuals have higher plasma concentrations of IL-7 when compared to normal weight individuals of similar ages, which, to-gether with the observed correlations and baseline differences between OG and NWG, suggest that excess body fat is associated with increased plasma concentrations of this cytokine. Additionally, CT can improve body com-position and physical fitness in middle-aged obese indi-viduals, although it is not possible to state that it induced decreases in plasma IL-7 concentrations by probabilistic statistics. However, the effect size analysis suggests that CT tends to induce a threefold greater magnitude of IL-7 decrease in OT when compared to OG.

The behavior of IL-7 has been shown to be quite complex in research with humans. Some studies that compared obese and eutrophic individuals observed that this cytokine was increased in the circulation of individuals with morbid obesity¹⁷-¹⁹. These findings are similar to the present results of higher circulating concentrations of IL-7 in obese individuals, reinforcing the hypothesis that obesity may have an influence on increasing this cytokine in an attempt to reestablish ho-meostasis and counterbalance the inflammation generated by excess body fat. Furthermore, we observed pos-itive correlations between IL-7 and body weight, BMI, and fat mass, which shows the importance and influ-ence of the relationship between weight control and body composition on the concentration of this cytokine.

However, other studies observe different results, with a decrease in circulating IL-7 in a group of obese elderly diabetics when compared to a eutrophic middle-aged group²⁰, and in young obese women without comorbid-ities when evaluated with middle-aged eutrophic wom-en²¹. Certain studies have not yet observed differences between middle-aged women with metabolic syndrome compared to healthy overweight women²² and among overweight and normal weight young women²³. Differ-ences between populations may have influenced these results, such as the discrepant ages of obese diabetic el-derly individuals when compared to a eutrophic mid-dle-aged group²⁰, or even high adiposity in both groups in the case of women with metabolic syndrome compared to women without metabolic syndrome, with both groups being characterized as overweight²².

Regarding the results of the experimental period, in the present study, we observed the effectiveness of CT in improving several components of physical fit-ness and body composition that are normally observed through the practice of this type of training¹⁰,²⁴,²⁵. For plasma concentrations of IL-7, although a reduction of almost 30% was observed in OT, it is not possible to state that this reduction occurred exclusively due to training, since in the OC group we also observed reductions in this cytokine. This decrease in IL-7 oc-curring in OC may be explained by the influence of several other factors that can influence inflammato-ry and immunological responses, such as the seasons, sleep quality and stress control. Improved sleep and reduced stress are factors that beneficially influence the neuroendocrine system, energy expenditure, appetite/ hunger, and consequently, metabolism and the immune system¹,². Since these factors were not controlled in the study due to its experimental and longitudinal nature, their influence on the results cannot be ruled out. However, the effect size results show that OT shows a greater effect on IL-7, which, together with other ben-efits influenced by CT, encourages us to speculate that this reduction observed in the OT group is associated with body composition and especially with physical fit-ness improvements. However, effect size complements, but does not replace, inferential results, and such find-ings should be interpreted as indicative or exploratory.

Studies that evaluated the effects of physical exer-cise on the expression of muscle IL-7 observed that both in mice of both sexes that underwent 12 weeks of CT²⁶, as young men who performed 11 weeks of strenght training⁴ showed an increase in the muscular expression of this cytokine, which may characterize it as a myokine. These results of increased expression of muscle IL-7 differ from the indication of a decrease in the average in the OT group, probably due to the fact that we analyzed the concentrations of IL-7 in plasma, and blood factors are affected by various tissues, as well as obesity and low-grade inflammation². Additionally, circulating factors induced by physical exercise, such as myokines, tend to increase during or shortly after the training session². This fact is corroborated by the results of increased IL-7 in the blood of young people after 30 minutes of the last section of 12 weeks of strength training²⁷. Since we collected samples 48 hours after the last session of the CT program, a time when there is normally no longer an acute influence of exercise on the secretion of products into the bloodstream, this would explain why our results were divergent.

One result that draws attention when comparing NWG and OG is that we saw no differences in carbo-hydrate intake and total calories between the groups. However, the anthropometric and body composition differences observed between NWG and OG may be partly justified by the higher lipid consumption of obese individuals. A higher consumption of fat, especially saturated fat, is already well established as an inflammatory inducer. The type of carbohydrate consumption, which, depending on the type has large amounts of fiber, for example, could also influence the intestinal microbiota, inflammation, and body weight²⁸. Additionally, the sample size and the way the diet was analyzed in a semi-quantitative manner (although val-idated and widely used, may present problems) may have influenced the results.

The present study also presents as a limitation the low number of subjects analyzed; however, our cross-sec-tional results still converge with some of the studies that show lower plasma IL-7 in some populations. Experi-mental studies with a larger number of subjects analyzed should be carried out to confirm the findings in relation to IL-7. Another limiting factor is that the sample con-sisted of both men and women, with an imbalance in the number of subjects of each sex within each group. But the fact that the women were in menopause may have minimized these gender differences.

In summary, the results of this study indicate that middle-aged obese insufficiently active individuals have higher circulating concentrations of IL-7 when compared with subjects of normal weight and the same age, suggesting that elevated body weight and fat are associated with an increase in this cytokine. Further-more, 16 weeks of CT improves cardiorespiratory fit-ness and maximum strength, as well as reducing weight and body fat. Although the effect size for IL-7 was larger in the OT group, probabilistic statistics did not show a significant effect. Further studies with a larger number of participants should be conducted to evaluate the effects of CT and other types of training on IL-7.

• Funding
  The study was supported by São Paulo State Research Support Foundation (Fundação de Amparo à Pesquisa do Estado de São Pau-lo - FAPESP) - São Paulo/Brazil - Regular Research Grants - Process: 2016/08751-3 and 2017/06643-1; Coordination for the Improvement of Higher Education Personnel (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES) - Bra-zil - Financing Code 001; National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvi-mento Científico e Tecnológico - CNPQ) - Brazil - Financing Code 303571/2018-7 and 307985/2022-9.

Declaration regarding the use of artificial intelligence tools in the article writing process

The authors did not use artificial intelligence tools for preparation of the manuscript.

Acknowledgments

The authors thank the participants and the funding agencies.

Availability of research data and other materials

After publication the data will be available on demand to authors

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Edited by

• Editor in Chief
  Raphael Ritti-Dias
  Nove de Julho University. São Paulo, São Paulo, Brazil.

• Section editor
  Breno Quintella Farah https://orcid.org/0000-0003-2286-5892
  Federal Rural University of Pernambuco, Recife, Pernambuco, Brazil

Reviewers’ assessment

The authors and/or reviewers did not authorize the publication of either of the two reviews.

• peer review recommendation:

History

• reviwed
  15 Oct 2025

Publication Dates

• Publication in this collection
  06 July 2026
• Date of issue
  2026

History

• Received
  03 Oct 2025
• reviwed
  15 Oct 2025
• Accepted
  17 Dec 2025