EFFECTS OF NONLINEAR RESISTANCE AND AEROBIC INTERVAL TRAINING ON CYTOKINES AND INSULIN RESISTANCE IN SEDENTARY MEN WHO ARE OBESE MAHMOUD NIKSERESHT,1 HAMID AGHA-ALINEJAD,2 MOHAMMAD A. AZARBAYJANI,1 KHOSROW EBRAHIM3
AND
1
Department of Exercise Physiology, Islamic Azad University, Central Tehran Branch, Tehran, Iran; 2Department of Physical Education, Tarbiat Modares University, Tehran, Iran; and 3Department of Sport and Exercise Physiology, Faculty of Physical Education, Shahid Beheshti University, Tehran, Iran ABSTRACT
Nikseresht, M, Agha-Alinejad, H, Azarbayjani, MA, and Ebrahim, K. Effects of nonlinear resistance and aerobic interval training on cytokines and insulin resistance in sedentary men who are obese. J Strength Cond Res 28(9): 2560–2568, 2014—Regular exercise training has been shown to reduce systemic inflammation, but there is limited research directly comparing different types of training. The purpose of this study was to compare the effects of nonlinear resistance training (NRT) and aerobic interval training (AIT) on serum interleukin-10 (IL-10), IL-20, and tumor necrosis factor-a (TNF-a) levels, insulin resistance index (homeostasis model assessment of insulin resistance), and aerobic capacity in middle-aged men who are obese. Sedentary volunteers were assigned to NRT (n = 12), AIT (n = 12), and (CON, n = 10) control groups. The experimental groups performed 3 weekly sessions for 12 weeks, whereas the CON grouped maintained a sedentary lifestyle. Nonlinear resistance training consisted of 40–65 minutes of weight training at different intensities with flexible periodization. Aerobic interval training consisted of running on a treadmill (4 sets of 4 minutes at 80– 90% of maximal heart rate, with 3-minute recovery intervals). Serum IL-10, IL-20, and TNF-a levels did not change significantly in response to training (all p . 0.05), but IL-10:TNF-a ratio increased significantly with AIT compared with CON (2.95 6 0.84 vs. 2.52 6 0.65; p = 0.02). After the training period, maximal oxygen uptake increased significantly in AIT and NRT compared with CON (both p , 0.001; 46.7 6 5.9, 45.1 6 3.2, and 41.1 6 4.7 ml$kg21$min21, respectively) and in AIT than in NRT (p = 0.001). The 2 exercise programs were equally effective at reducing insulin resistance (homeostasis model assessment for insulin resistance) (both p # 0.05; AIT: 0.84 6 0.34, Address correspondence to Mahmoud Nikseresht, Nikserasht@gmail. com. 28(9)/2560–2568 Journal of Strength and Conditioning Research Ó 2014 National Strength and Conditioning Association
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NRT: 0.84 6 0.27, and CON: 1.62 6 0.56) and fasting insulin levels (both p # 0.05; AIT: 3.61 6 1.48, NRT: 3.66 6 0.92, and CON: 6.20 6 2.64 mU$ml21), but the AIT seems to have better anti-inflammatory effects (as indicated by the IL-10:TNF-a ratio) compared with NRT.
KEY WORDS exercise training, IL-10:TNF-a ratio, inflammation, interleukin, obesity INTRODUCTION
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besity is associated with the development of insulin resistance, type 2 diabetes mellitus, and cardiovascular disease (9). Circulating levels of tumor necrosis factor-a (TNF-a) and interleukin-10 (IL-10) are elevated in obese subjects (3,6). It is known that high levels of inflammatory markers are strong predictors of mortality risk in middle-aged people (2). Exercise can impede the accumulation of adipose tissue directly through increasing energy expenditure and can promote cardiovascular health by improving the blood lipid profile, which is presumed to limit the production of atherosclerosis. However, the protective effect of regular exercise training against chronic diseases can be additionally ascribed to the anti-inflammatory effects of exercise (4). But, there are, at present, no known definitive therapies for treating chronic inflammation. Regular exercise training promotes anti-inflammatory effects in skeletal muscles and adipose tissue (38). It has been shown that aerobic exercise training induces suppression of TNF-a and thereby offers protection against TNFa–induced insulin resistance in healthy young sedentary adults (42). In contrast, 16 weeks of endurance training in middle-aged healthy men has not affected TNF-a (31). Also, studies have shown increases in the plasma concentration of IL-10 after aerobic exercise training in overweight people with heart diseases or diabetes (16,24), a response that can contribute to the anti-inflammatory milieu and also be an important mediator of the anti-inflammatory effects of exercise training. Interleukin-10 has been postulated as the main
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in obese women. But to the authors’ knowledge, no previous TABLE 1. Nonlinear resistance training protocol.* study has investigated the response of IL-20 to exercise Exercises Very light Light Moderate Heavy Very heavy training. In general, although Knee extension 40/20 3 1† 60/15 3 2 75/10 3 3 90/4 3 3 95/2 3 4 aerobic exercise training has Bench press 40/20 3 1 75/10 3 3 90/4 3 3 95/2 3 4 demonstrated the ability to Incline bench press 60/15 3 2 reduce chronic inflammation Seated row 40/20 3 1 60/15 3 2 75/10 3 3 90/4 3 3 95/2 3 4 Dead lift 40/20 3 1 60/15 3 2 75/10 3 3 90/4 3 3 95/2 3 4 in a number of populations, Pulley crunches 1 3 20 2 3 20 3 3 15 3 3 18 3 3 20 the capacity of resistance trainLat pull-downs 60/15 3 2 ing (RT) to alter markers of Calf raise 40/20 3 1 60/15 3 2 75/10 3 2 90/4 3 2 inflammation has not been Hamstring curl 40/20 3 1 60/15 3 2 75/10 3 2 90/4 3 2 fully investigated. To summaPress behind neck 40/20 3 1 60/15 3 2 75/10 3 2 90/4 3 2 Upright row 40/20 3 1 60/15 3 2 75/10 3 2 90/4 3 2 rize, there are a few studies that Arm curl 40/20 3 1 60/15 3 2 75/10 3 2 90/4 3 2 have reported no changes in TNF-a responses with RT in *Length of rest period: very light = 1 minutes; light and moderate = 1–2 minutes; heavy = sedentary and healthy men 3–4 minutes; very heavy = 5–7 minutes. †1 set 3 20 repetitions, 40% 1RM. (17,25,31,32,43). Similarly, IL10 concentrations did not change after exercise training (combined aerobic and resismolecule responsible for the initiation of anti-inflammatory tance) in patients with type 2 diabetes mellitus (36,44). reactions, especially the inhibition of the changes mediated Physiological responses to aerobic exercise training, as by TNF-a (35). Interleukin-20 is a pleiotropic cytokine, prefwell as cytokine responses, differ from RT (26). In addition, erentially expressed in monocytes, epithelial cells, and endothe cytokine response may vary according to the type of thelial cells (21), with potent inflammatory, angiogenic, and exercise, intensity, duration, and recovery between exercise chemoattractive effects (45). The amino acid sequences of bouts, and it also depends on the training status (34). DifferIL-20 and IL-10 are 28% identical, and IL-20 was conseent types of RT induce different physiological adaptations. quently classified as a member of the IL-10 family. Although Nonlinear RT (NRT) is a type of RT that produces greater much remains to be explained about the physiological and day-to-day variation in the training stimuli and induces less pathogenic mechanisms of action of IL-20, current data supmuscle damage (28). It is important because the inflammaport its association with several diseases, including psoriasis, tory response to damaging exercise is in addition to the rheumatoid arthritis, and atherosclerosis. Interleukin-20– inflammatory response to exercise without damage. Also, induced accumulation of inflammatory markers in monothe NRT is at least as effective or possibly more effective cytes and endothelial cells could be involved in the onset than the linear periodization for maximal strength gains and progression of atherosclerosis (45). Maiorino et al. (33) (14). No previous study has investigated the effects of this reported that caloric restriction–induced weight loss (more type of training on inflammatory markers. It is hypothesized than 10% of original weight) reduced circulating IL-20 levels that an intervention using NRT will improve markers of inflammation. On the other hand, researchers have demonstrated that high-intensity, but not moderate-intensity, aeroTABLE 2. Mesocycle with emphasis on endurance and general preparation.* bic training resulted in a significant reduction in TNF-a in Week healthy and sedentary adults (42). Thus, we also used the 1 2 3 4 5 6 7 8 9 10 11 12 intensive aerobic interval trainWorkout sequence ing (AIT) because it has been Day 1 L L M VL M L VL H L M L VL shown that moderate longDay 2 M VL H H M M M VL L M M H term exercise seems to have Day 3 L H L L L H L M VH VL VL L no effect on adipokine gene *L = light-intensity workout; M = moderate-intensity workout; VL = very light–intensity expression (i.e., TNF-a) or on workout; H = heavy-intensity workout; VH = very heavy–intensity workout. An active rest plasma levels except for leptin day was used after any workout. (40). It is now clear that regular exercise training changes VOLUME 28 | NUMBER 9 | SEPTEMBER 2014 |
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METHODS Experimental Approach to the Problem
0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 7.9 4.0†z§ 5.2†z§ 3.2†z§ 11.0†z§¶ 7.3†z§¶
92.2 28.0 102.2 40.6 52.5 25.3
6 6 6 6 6 6
7.8 3.2 5.7 6.3 8.3 5.9
89.0 24.9 95.4 46.7 53.9 32.5
6 6 6 6 6 6
7.4†z§k 2.9†z§ 4.0†z§ 5.9†z§k 9.2 6.2†z§
This study was undertaken to compare the effects of NRT and AIT on serum cytokine concentrations, insulin resistance, and functional capacity in sedentary and men who are obese. Participants first were matched by age and percent body fat, then randomly assigned to one of the 3 groups, namely, NRT group, AIT group, and control group. To examine a long-term training scenario, we used a period of 12 weeks of training programs under carefully monitored conditions. The volume of training was matched by calorie expenditure using a heart rate monitor (Polar RCX 5 sd Run; Electro Inc., NY, USA), to make sure identical between the 2 training programs. The algorithm used in this software for the calorie expenditure estimation is based on the type of exercise, V_ O2max, activity level, age, gender, and body mass index. However, it is not the best method of determining exercise calorie expenditure. Participants in the control group continued their normal sedentary life. Basal blood samples were collected to determine serum IL-10, IL-20, TNF-a, glucose, and insulin concentrations before and after the 12 weeks of intervention period. Also, the participants were asked to consume a similar diet for at least 48 hours before blood sampling at baseline and after the training period. Subjects *i = intervention; t = time. Data are reported as mean 6 SD. †Significant difference within group (p # 0.05). zSignificant difference between groups (p # 0.05). §Control. ¶Aerobic interval training. kNonlinear resistance training.
6 6 6 6 6 6 Body mass (kg) Fat mass (kg) Waist circumference (cm) V_ O2 max (ml$kg21$min21) 1RM bench press (kg) 1RM knee extension (kg)
94.8 28.2 101.8 41.6 53.9 27.9
Before Variables
5.8 2.6 6.4 4.9 11.3 6.2
95.2 28.7 101.2 41.1 50.5 28.5
6 6 6 6 6 6
5.8 3.0 5.0 4.7 8.3 6.1
88.3 26.5 99.0 42.7 46.7 23.7
6 6 6 6 6 6
7.9 4.3 4.9 4.9 12.0 4.0
87.5 24.0 93.8 45.1 74.5 47.3
6 6 6 6 6 6
Before After Before After
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inflammatory biomarkers, but it is still not clear what type of training is most appropriate. Therefore, the present study was designed to determine and compare the effects of 2 different 12-week exercise training interventions (NRT and AIT) on maximal oxygen uptake, fat mass, waist circumference, selected serum cytokines (TNF-a, IL-10, and IL-20) and insulin resistance in men who are obese.
0.089 0.099 0.082 0.468 0.216 0.018
i3t t After
i
p Aerobic interval training Nonlinear resistance training Control
TABLE 3. Physiological characteristic changes of the participants before and after 12 weeks of aerobic interval training, nonlinear resistance training, and control condition.*
Exercise Training and the IL-10:TNF-a Ratio
Thirty-four otherwise healthy men who are obese (age range, 34–46 years) were randomly assigned to an NRT (age, 40.4 6 5.2 years; n = 12), AIT (age, 39.6 6 3.7 years; n = 12), or CON (age, 38.9 6 4.1 years; n = 10) group. The inclusion criteria were as follows: nonsmokers, no regular exercise for at least the past 6 months, no regular consumption of medication, obese (percent body fat . 25) (19), and no history of any kind of medical condition that would prevent them from participating in the exercise intervention. The experimental protocol was approved by the Research Ethics Committee at the Islamic Azad University, Central Tehran Branch, Tehran, Iran. The risks of the study were explained to the participants before participation, and each participant signed an institutionally approved informed consent document before participation in the investigation. Procedures
All participants were asked to complete a personal health and medical history questionnaire, which served as a screening tool. Participants were familiarized with all testing procedures before the start of the testing. A maximal oxygen uptake (V_ O2max) test, maximal strength and body
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0.650 0.014 0.006 0.084 0.256 0.137 0.020 0.078 0.001 0.001 0.041 0.011 0.025 0.005 0.140 0.012 0.003 0.655 0.134 0.835 0.967 6 6 6 6 6 6 6 *i = intervention; t = time; HOMA-IR = homeostasis model assessment of insulin resistance. Data are reported as mean 6 SD. †Significant difference within group (p # 0.05). zSignificant difference between groups (p # 0.05). §Control.
5.36 3.61 0.84 7.32 20.78 2.60 2.95 0.04 1.72 0.44 0.82 3.21 0.64 0.59 6 6 6 6 6 6 6 5.62 5.52 1.39 6.68 19.33 2.99 2.33 0.07 0.92†z§ 0.27†z§ 0.64† 2.04† 0.53† 0.62† 6 6 6 6 6 6 6 6 6 6 6 6 6 6 5.92 6.60 1.72 7.31 18.66 2.90 2.66
0.05 1.86 0.42 1.06 1.09 0.74 0.75
5.81 6.20 1.62 7.17 19.23 2.96 2.52 6 6 6 6 6 6 6 Glucose (mmol$L21) Insulin (mU$ml21) HOMA-IR IL-10 (pg$ml21) IL-20 (pg$ml21) TNF-a (pg$ml21) IL10:TNF-a (ratio)
0.09 2.64 0.56 0.81 4.07 0.64 0.65
6.21 5.80 1.49 7.06 19.36 3.00 2.40
0.04 1.58 0.47 0.71 2.55 0.46 0.48
5.63 3.66 0.84 7.46 22.55 2.66 2.90 6 6 6 6 6 6 6
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composition assessments, measurement of serum cytokine levels (IL-10, IL-20, and TNF-a), and insulin resistance index were performed before and after the 12 weeks of training period.
0.03 1.48†z§ 0.34†z§ 0.99† 3.34 0.54† 0.84†z§
t i After
i3t p Aerobic interval training Nonlinear resistance training Control
TABLE 4. Serum cytokines levels and insulin resistance changes before and after 12 weeks of aerobic interval training, nonlinear resistance training, and control condition.*
Journal of Strength and Conditioning Research
Maximal Strength and V_ O2max Assessments. After familiarization, participants were asked to report to the laboratory for an additional test session designed to determine 1 repetition maximum (1RM) for the bench press and knee extension. After the warm-up, participants performed the 1RM test using the Brzycki method (28). The warm-up consisted of riding a stationary bicycle for 10 minutes, 2 sets of progressive resistance exercises similar to the actual exercises used in the main experiment, and 3 minutes of rest accompanied by some light stretching exercises. V_ O2max was estimated using the Bruce treadmill protocol (5) 2 days after the maximum strength tests. Anthropometric. Each participant’s body mass was measured while they were wearing underclothes on a balance scale (Seca, 700 Mechanical Column Scales, United Kingdom) calibrated to the nearest 0.1 kg after a 12-hour fast. Each participant’s waist circumference was measured midway between the lowest rib and the iliac crest. Subcutaneous skinfold thickness was measured sequentially, in triplicate, at the chest, abdomen, and thigh using a skinfold caliper (Lange; Country Technology, Gays Mills, WI, USA) and standard technique. The average of 3 measures for each skinfold was used. Percent body fat was estimated using the equation of Jackson and Pollock (22). Then, fat mass was estimated (body mass 3 percent body fat) (28). The same investigator performed all skinfold and girth measurements assessments. Blood Sampling. Blood samples (approximately 10 ml) were obtained from the antecubital vein in the morning (6:00 to 8:00 hours), after a 12-hour overnight fast before and after the training period. Before blood sampling, volunteers were asked to avoid from strenuous physical activity for at least 4 days. Participants were also asked whether they had experienced any symptoms of illness in the past 4 days or had taken any medication in this period. If a participant indicated that this was the case, a new appointment was made 4 days later. Posttraining blood samples from participants in the training groups were obtained 4 days after their last exercise session. Whole blood was centrifuged at 3,000 rpm (48 C) for 15 minutes, and the serum was removed and stored at 2808 C until subsequent analysis. Biochemical Analyses
Cytokines Analysis. The concentrations of IL-10, IL-20, and TNF-a were measured in serum samples in duplicate by enzyme linked immunosorbent assay (ELISA), according to the specifications of the manufacturer (Quantikine High Sensitivity Kit; R&D Systems, Minneapolis, MN, USA). The intraassay and interassay coefficients of variation were 5.0 and 7.3% VOLUME 28 | NUMBER 9 | SEPTEMBER 2014 |
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Exercise Training and the IL-10:TNF-a Ratio 80–90% of maximal heart rate with 3-minute recovery intervals at 55–65% of maximal heart rate, 3 days per week, for 12 weeks. Each training session was started with a general warm-up and finished with a cooldown. The exercise intensity was controlled by the authors, using a heart rate monitor (Polar RCX5sd Run), who ensured the correct exercise heart rates throughout the trial. The training sessions were performed in the university laboratory and were supervised by the researchers. Statistical Analyses
All data analyses were performed using SPSS 16.0 (SPSS, Inc., Chicago, IL, USA). Values are expressed as mean 6 SD. Normality of distribution was tested using the Shapiro–Wilk test. A 2-factor repeatedmeasures analysis of variance Figure 1. Percent changes in cytokines and insulin resistance after 12 weeks of aerobic interval training, nonlinear resistance training, and control condition. #Significant difference between group (P # 0.05). c, control group. (ANOVA) was used to determine the differences between interventions and across time. for IL-10, 6.2 and 9.0% for IL-20, 4.3 and 7.3% for TNF-a, The first factor was “intervention” (between-group factor) respectively. and had 3 levels (AIT, NRT, and CON), and the second factor was “time” (repeated-measures factor) and had 2 levels Insulin Resistance Assay. Serum glucose concentration was (before and after 12 weeks). When the ANOVA detected measured using the glucose oxidase method (glucose B-test; significant interactions among means (intervention 3 time), Wako Pure Chemical, Osaka, Japan). The serum insulin the Bonferroni analysis was used post hoc to identify where concentration was determined in duplicate by ELISA (Q-1 those differences occurred. Statistical power calculations for DIAPLUS kit; DIAPLUS Inc., NY, USA). Both the intrathis study ranged from 0.72 to 0.85. The level of significance assay and interassay coefficients of variation was 5.1%. was set at p # 0.05 for all statistical comparisons. Before and after the intervention, insulin resistance in the fasting state was determined using a homeostasis model RESULTS assessment (HOMA-IR) and was calculated from fasting Participant Physiological Characteristics insulin (IF) and fasting glucose (GF) as follows: HOMA-IR = Physiological characteristics of the participants at baseline (IF 3 GF)/22.5 (1). The units for IF and GF were microunits and after 12 weeks of training are presented in Table 3. After per milliliter and millimoles per liter, respectively. the training period, significant differences in body mass, fat Training Programs mass, waist circumference, V_ O2max, bench press, and knee Nonlinear Resistance Training. The NRT was with emphasis extension maximal strength were detected by ANOVA (all on endurance and general preparation and consisted of 40– p # 0.05). Post hoc tests demonstrated that significant de65 minutes of weight training per day, 3 days per week, for creases were found in the fat mass and waist circumference 12 weeks at different intensities. This training has already for both the experimental groups compared with the CON been proposed by Kraemer and Fleck (28) and the details (all p , 0.01), but no significant difference between the are shown in Tables 1 and 2. both training groups (both p . 0.05). Body mass loss was greater for the AIT group compared with other groups (both p , 0.01). There was significant increases in V_ O2max Aerobic Interval Training. The AIT consisted of running on for both training groups compared with the CON group a treadmill, consisting of 4 sets of 4 minutes at an intensity of
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Journal of Strength and Conditioning Research (both p , 0.01), but the increase was significantly higher with AIT than with NRT (p = 0.001). Maximal strength for bench press and knee extension were significantly increased with NRT compared with other groups (all p , 0.001) and with AIT compared with the CON for knee extension only (p = 0.001). However, after the intervention period, there was no improvement in these variables for the CON. Cytokines and Insulin Resistance
Serum cytokines, insulin, and glucose concentrations of the participants at baseline and after 12 weeks of training are presented in Table 4. There was no significant difference found between the conditions for glucose (Table 4). However, there were significant differences in fasting insulin levels and HOMA-IR detected by ANOVA. Post hoc tests showed that significant decreases in these variables for both the experimental groups (all p # 0.05) compared with the CON, although changes in fasting insulin levels and HOMA-IR were not significantly different between the 2 training groups. There were no significant differences found between the conditions for IL-10, IL-20, and TNF-a by ANOVA (Table 4). There were significant main effects of time (p # 0.05, Table 4), and post hoc paired t-test demonstrated a significant increase in IL-10 (AIT: 10.2%; p = 0.02 and NRT: 6.1%; p = 0.04), decrease in TNF-a (AIT: 11.9%; p = 0.01 and NRT: 10.7%; p = 0.04) after 12 weeks in both training, and increase in IL-20 only with NRT (17.8%; p = 0.001) (Figure 1). There was a significant intervention 3 time interaction for IL-10: TNF-a ratio (p = 0.020; Table 4), and post hoc analysis showed that the ratio in AIT was greater than that in the CON condition after 12 weeks (p = 0.02), but NRT tended to increase (p = 0.07). The ratio was significantly increased in NRT compared with the pretest (p = 0.01). However, after the intervention period, there was no change in these variables for the CON.
DISCUSSION This is the first study to compare the effects of NRT and AIT on inflammatory markers in sedentary men who are obese. In this study, the NRT and AIT programs (with similar calorie expenditure) were equally effective at reducing insulin resistance, fasting insulin levels, fat mass, and waist circumference. There were no significant changes in serum IL-10, IL-20, and TNF-a levels after 12 weeks of NRT and AIT, but the serum IL-10:TNF-a ratio was significantly increased with AIT when compared with the control condition. The positive effects of NRT in this study were demonstrated by a significant increase in muscular strength (as measured by bench press and knee extension 1RM). This improvement in muscular strength with NRT was accompanied by an improvement in V_ O2max and reductions in fat mass and waist circumference. We found a 6.3% improvement in V_ O2max after NRT, which supports the finding of
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Gettman and Pollack (15). They reported that shortduration (8–20 weeks) weight training increased V_ O2max by 4 and 8% in men and women, respectively. In the present study, 12 weeks of NRT and AIT decreased insulin resistance by 48.5 and 40.8%, respectively (Figure 1). These results support the findings of previous studies that reported reductions in insulin resistance after 12 weeks of endurance and RT in sedentary men who are obese (1) and in young recreationally active adult men and women, after a 6week period of aerobic training (18). Several mechanisms have been suggested to be responsible for the decreases in insulin resistance after exercise training, including increased postreceptor insulin signaling (10), increased glucose transporter protein and messenger RNA synthesis (11), and increased activity of glycogen synthase and hexokinase (13). The mechanisms responsible for the effect of RT on glucose homeostasis and insulin resistance are similar to those associated with the adaptation to aerobic exercise training (7). However, the mechanism responsible for the decreases in insulin resistance after training cannot be established from the present study. Although insulin resistance was improved with decreases in fat mass and waist circumference in the experimental groups, changes in insulin resistance were independent of changes in body composition (data not shown), as reported by others (12,39). This suggests that RT and endurance training decrease insulin resistance independent of the alterations in body composition. Twelve weeks of NRT and AIT did not significantly change serum IL-10 and TNF-a levels when compared with the control group. These results were consistent with previous studies, indicating no significant change in TNF-a after 16 weeks of endurance, resistance, and concurrent training in sedentary middle-aged healthy men (31,32). In contrast, some other studies showed that the levels of TNF-a were significantly lower after 12 weeks of exercise training when adjusting for baseline levels (20). For example, Kohut et al. (27) reported a significant reduction in this cytokine after 10 months of aerobic exercise training in older adults. A few studies on exercise training that have investigated changes in IL-10 have also reported conflicting results. Cheema et al. (8) suggested that 12 weeks of RT does not increase circulating IL-10 in kidney patients, whereas Kadoglou et al. (24) reported that plasma levels of IL-10 increased in response to 6 months of aerobic exercise training in overweight patients with type 2 diabetes mellitus. For the most part, intervention studies in participants with elevated inflammation as a result of chronic disease or obesity showed a favorable exercise training effect on specific inflammatory biomarkers. For example, in patients with coronary heart disease participating in cardiac rehabilitation, 12 weeks of aerobic exercise training resulted in increases in IL-10 (16). Similarly, 12 weeks of aerobic exercise training reduced TNF-a levels in patients with chronic heart failure (30). Recently, Santos et al. (41) reported that the levels of TNF-a and the ratio of TNF-a to IL-10 were decreased, whereas IL-10 levels VOLUME 28 | NUMBER 9 | SEPTEMBER 2014 |
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Exercise Training and the IL-10:TNF-a Ratio increased after moderate exercise training in sedentary healthy elderly men. These discrepant results may be attributed to diversity in the initial values of cytokines, differences in the timing of blood sampling, variation in the exercise protocols, and differences in subject populations. It seems that long-duration (more than 6 months) exercise training has more potential to decrease inflammation. Also, it is possible that a reduced proinflammatory cytokine response to exercise training is easier to achieve in elderly people and patients compared with healthy young individuals. Factors such as aging and the most important cardiovascular disease and type 2 diabetes mellitus have increased the levels of these inflammatory markers. Therefore, it is possible that regular exercise training is most effective at reducing the levels of these inflammatory markers in individuals with elevated levels to begin with. In addition, the results of randomized controlled trials have shown that chronic exercise training can reduce inflammation in people with higher baseline levels and those who exhibited weight loss after exercise training, whereas high levels of physical activity have little or no effect on inflammatory markers in healthy subjects (4). Further studies are needed to understand the anti-inflammatory effects of exercise training. It has been adopted that the IL-10:TNF-a ratio is an indicator of inflammatory status and disease-associated morbidity, with lower values being related to poorer prognosis. We demonstrated that even in healthy men who are obese, the AIT is able to increase the IL-10:TNF-a ratio compared with the CON (Figure 1). These finding suggest that the antiinflammatory effects of AIT are greater than those of NRT. The increase in the IL-10:TNF-a ratio with AIT may be attributed to the high intensity of training in this group. Peake et al. (37) reported that higher exercise intensity has a greater effect on IL-10 and IL-1ra responses to downhill running in well-trained runners. As an explanation of their findings, the authors suggest that higher exercise intensity could increase stress hormones and IL-6, leading to higher antiinflammatory cytokine responses (37). The mechanism responsible for the effects of the AIT on the levels of IL-10: TNF-a ratio in this study might be because of the reduction in body mass or an increase in V_ O2max or a combination of both in this training group. Studies report that an inverse relationship exists between biomarkers of inflammation and direct measurement of V_ O2max assessed during an exercise test (23,29). In this study, V_ O2max was significantly increased in both AIT and NRT (albeit less in NRT), but the IL-10: TNF-a ratio was significantly increased only in AIT. Thus, it can be suggested that perhaps a greater increase in V_ O2max with NRT (equal to AIT) can lead to similar effects. After the training period, there was no difference between training and control groups for IL-20 (further highlighted by the lack of difference between groups in percentage change shown in Figure 1). A significant decrease in circulating IL-20 levels from 152 (range, 112–184 pg$ml21) to 134 (range, 125–153 pg$ml21) pg$ml21 was observed after a 6-month
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diet-induced weight loss program in obese women (33). As an explanation for this result, we suggest that baseline levels of data should be considered because the initial level of serum IL-20 levels in the present study was 19.3 6 3.2 pg$ml21, which is less than the values reported in the study of Maiorino et al. (33). In addition, these conflicting results may be the results of differences in the type of intervention (exercise vs. diet) and differences in participants (men vs. women). Also, in this study, it was found that the initial concentrations of these cytokines is within the normal range based on the values defined by the manufacturer Kits with nonobese and healthy individuals. Thus, it seems that regular exercise training has less potential to significant changes in the normal concentration of these cytokines. A limitation of the present study is that other cytokines and inflammatory biomarkers, such as adiponectin, C-reactive protein, and IL-6, were not measured because it is possible that the NRT or AIT may have improved the activity of these. Hence, future studies should further investigate this issue.
PRACTICAL APPLICATIONS In summary, despite improvements in insulin resistance, fat _ O2max, 12 weeks of AIT and mass, waist circumference, and V NRT had no effect on serum IL-10, IL-20, and TNF-a levels. However, the serum IL-10:TNF-a ratio was increased after AIT compared with the control group. It seems that the antiinflammatory effect (for this measure at least) of AIT is better than that of NRT in otherwise healthy men who are obese. _ O2max This improvement is probably because of the higher V and lower body mass after the AIT. Collectively, these data suggest that the AIT could be a good therapy to reduce risk factors associated with type 2 diabetes mellitus and cardiovascular diseases in middle-aged men who are obese through the modification of the serum IL-10:TNF-a ratio. Also, it seems like both types of training are beneficial overall (e.g., all improvements listed above), but AIT is the only one that had some effects on one (but not all) of the anti-inflammatory markers. These findings do not support the idea that an NRT regimen with emphasis on endurance and general preparation decreases systemic inflammation in healthy middleaged men who are obese. We recommend that this issue be investigated further in future studies.
ACKNOWLEDGMENTS The authors wish to thank the volunteers for their enthusiastic participation in this study and also would like to thank Prof. Michael Gleeson and Dr. Glen Davison for reading the manuscript.
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Exercise Training and the IL-10:TNF-a Ratio 39. Poehlman, ET, Dvorak, RV, Denio, WF, Brochu, M, and Ades, PA. Effects of resistance training and endurance training on insulin sensitivity in non obese, young women. A controlled randomized trail. J Clin Endocrinol Metab 85: 2463–2468, 2000. 40. Polak, J, Klimcakova, E, Moro, C, Viguerie, N, Berlan, M, Hejnova, J, Richterova, B, Kraus, I, Langin, D, and Stich, V. Effect of aerobic training on plasma levels and subcutaneous abdominal adipose tissue gene expression of adiponectin, leptin, interleukin 6, and tumor necrosis factor alpha in obese women. Metabolism 55: 1375– 1381, 2006. 41. Santos, RV, Viana, VA, Boscolo, RA, Marques, VG, Santana, MG, Lira, FS, Tufik, S, and de Mello, MT. Moderate exercise training modulates cytokine profile and sleep in elderly people. Cytokine 60: 731–735, 2012.
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AND
1
Department of Exercise Physiology, Islamic Azad University, Central Tehran Branch, Tehran, Iran; 2Department of Physical Education, Tarbiat Modares University, Tehran, Iran; and 3Department of Sport and Exercise Physiology, Faculty of Physical Education, Shahid Beheshti University, Tehran, Iran ABSTRACT
Nikseresht, M, Agha-Alinejad, H, Azarbayjani, MA, and Ebrahim, K. Effects of nonlinear resistance and aerobic interval training on cytokines and insulin resistance in sedentary men who are obese. J Strength Cond Res 28(9): 2560–2568, 2014—Regular exercise training has been shown to reduce systemic inflammation, but there is limited research directly comparing different types of training. The purpose of this study was to compare the effects of nonlinear resistance training (NRT) and aerobic interval training (AIT) on serum interleukin-10 (IL-10), IL-20, and tumor necrosis factor-a (TNF-a) levels, insulin resistance index (homeostasis model assessment of insulin resistance), and aerobic capacity in middle-aged men who are obese. Sedentary volunteers were assigned to NRT (n = 12), AIT (n = 12), and (CON, n = 10) control groups. The experimental groups performed 3 weekly sessions for 12 weeks, whereas the CON grouped maintained a sedentary lifestyle. Nonlinear resistance training consisted of 40–65 minutes of weight training at different intensities with flexible periodization. Aerobic interval training consisted of running on a treadmill (4 sets of 4 minutes at 80– 90% of maximal heart rate, with 3-minute recovery intervals). Serum IL-10, IL-20, and TNF-a levels did not change significantly in response to training (all p . 0.05), but IL-10:TNF-a ratio increased significantly with AIT compared with CON (2.95 6 0.84 vs. 2.52 6 0.65; p = 0.02). After the training period, maximal oxygen uptake increased significantly in AIT and NRT compared with CON (both p , 0.001; 46.7 6 5.9, 45.1 6 3.2, and 41.1 6 4.7 ml$kg21$min21, respectively) and in AIT than in NRT (p = 0.001). The 2 exercise programs were equally effective at reducing insulin resistance (homeostasis model assessment for insulin resistance) (both p # 0.05; AIT: 0.84 6 0.34, Address correspondence to Mahmoud Nikseresht, Nikserasht@gmail. com. 28(9)/2560–2568 Journal of Strength and Conditioning Research Ó 2014 National Strength and Conditioning Association
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NRT: 0.84 6 0.27, and CON: 1.62 6 0.56) and fasting insulin levels (both p # 0.05; AIT: 3.61 6 1.48, NRT: 3.66 6 0.92, and CON: 6.20 6 2.64 mU$ml21), but the AIT seems to have better anti-inflammatory effects (as indicated by the IL-10:TNF-a ratio) compared with NRT.
KEY WORDS exercise training, IL-10:TNF-a ratio, inflammation, interleukin, obesity INTRODUCTION
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besity is associated with the development of insulin resistance, type 2 diabetes mellitus, and cardiovascular disease (9). Circulating levels of tumor necrosis factor-a (TNF-a) and interleukin-10 (IL-10) are elevated in obese subjects (3,6). It is known that high levels of inflammatory markers are strong predictors of mortality risk in middle-aged people (2). Exercise can impede the accumulation of adipose tissue directly through increasing energy expenditure and can promote cardiovascular health by improving the blood lipid profile, which is presumed to limit the production of atherosclerosis. However, the protective effect of regular exercise training against chronic diseases can be additionally ascribed to the anti-inflammatory effects of exercise (4). But, there are, at present, no known definitive therapies for treating chronic inflammation. Regular exercise training promotes anti-inflammatory effects in skeletal muscles and adipose tissue (38). It has been shown that aerobic exercise training induces suppression of TNF-a and thereby offers protection against TNFa–induced insulin resistance in healthy young sedentary adults (42). In contrast, 16 weeks of endurance training in middle-aged healthy men has not affected TNF-a (31). Also, studies have shown increases in the plasma concentration of IL-10 after aerobic exercise training in overweight people with heart diseases or diabetes (16,24), a response that can contribute to the anti-inflammatory milieu and also be an important mediator of the anti-inflammatory effects of exercise training. Interleukin-10 has been postulated as the main
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in obese women. But to the authors’ knowledge, no previous TABLE 1. Nonlinear resistance training protocol.* study has investigated the response of IL-20 to exercise Exercises Very light Light Moderate Heavy Very heavy training. In general, although Knee extension 40/20 3 1† 60/15 3 2 75/10 3 3 90/4 3 3 95/2 3 4 aerobic exercise training has Bench press 40/20 3 1 75/10 3 3 90/4 3 3 95/2 3 4 demonstrated the ability to Incline bench press 60/15 3 2 reduce chronic inflammation Seated row 40/20 3 1 60/15 3 2 75/10 3 3 90/4 3 3 95/2 3 4 Dead lift 40/20 3 1 60/15 3 2 75/10 3 3 90/4 3 3 95/2 3 4 in a number of populations, Pulley crunches 1 3 20 2 3 20 3 3 15 3 3 18 3 3 20 the capacity of resistance trainLat pull-downs 60/15 3 2 ing (RT) to alter markers of Calf raise 40/20 3 1 60/15 3 2 75/10 3 2 90/4 3 2 inflammation has not been Hamstring curl 40/20 3 1 60/15 3 2 75/10 3 2 90/4 3 2 fully investigated. To summaPress behind neck 40/20 3 1 60/15 3 2 75/10 3 2 90/4 3 2 Upright row 40/20 3 1 60/15 3 2 75/10 3 2 90/4 3 2 rize, there are a few studies that Arm curl 40/20 3 1 60/15 3 2 75/10 3 2 90/4 3 2 have reported no changes in TNF-a responses with RT in *Length of rest period: very light = 1 minutes; light and moderate = 1–2 minutes; heavy = sedentary and healthy men 3–4 minutes; very heavy = 5–7 minutes. †1 set 3 20 repetitions, 40% 1RM. (17,25,31,32,43). Similarly, IL10 concentrations did not change after exercise training (combined aerobic and resismolecule responsible for the initiation of anti-inflammatory tance) in patients with type 2 diabetes mellitus (36,44). reactions, especially the inhibition of the changes mediated Physiological responses to aerobic exercise training, as by TNF-a (35). Interleukin-20 is a pleiotropic cytokine, prefwell as cytokine responses, differ from RT (26). In addition, erentially expressed in monocytes, epithelial cells, and endothe cytokine response may vary according to the type of thelial cells (21), with potent inflammatory, angiogenic, and exercise, intensity, duration, and recovery between exercise chemoattractive effects (45). The amino acid sequences of bouts, and it also depends on the training status (34). DifferIL-20 and IL-10 are 28% identical, and IL-20 was conseent types of RT induce different physiological adaptations. quently classified as a member of the IL-10 family. Although Nonlinear RT (NRT) is a type of RT that produces greater much remains to be explained about the physiological and day-to-day variation in the training stimuli and induces less pathogenic mechanisms of action of IL-20, current data supmuscle damage (28). It is important because the inflammaport its association with several diseases, including psoriasis, tory response to damaging exercise is in addition to the rheumatoid arthritis, and atherosclerosis. Interleukin-20– inflammatory response to exercise without damage. Also, induced accumulation of inflammatory markers in monothe NRT is at least as effective or possibly more effective cytes and endothelial cells could be involved in the onset than the linear periodization for maximal strength gains and progression of atherosclerosis (45). Maiorino et al. (33) (14). No previous study has investigated the effects of this reported that caloric restriction–induced weight loss (more type of training on inflammatory markers. It is hypothesized than 10% of original weight) reduced circulating IL-20 levels that an intervention using NRT will improve markers of inflammation. On the other hand, researchers have demonstrated that high-intensity, but not moderate-intensity, aeroTABLE 2. Mesocycle with emphasis on endurance and general preparation.* bic training resulted in a significant reduction in TNF-a in Week healthy and sedentary adults (42). Thus, we also used the 1 2 3 4 5 6 7 8 9 10 11 12 intensive aerobic interval trainWorkout sequence ing (AIT) because it has been Day 1 L L M VL M L VL H L M L VL shown that moderate longDay 2 M VL H H M M M VL L M M H term exercise seems to have Day 3 L H L L L H L M VH VL VL L no effect on adipokine gene *L = light-intensity workout; M = moderate-intensity workout; VL = very light–intensity expression (i.e., TNF-a) or on workout; H = heavy-intensity workout; VH = very heavy–intensity workout. An active rest plasma levels except for leptin day was used after any workout. (40). It is now clear that regular exercise training changes VOLUME 28 | NUMBER 9 | SEPTEMBER 2014 |
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METHODS Experimental Approach to the Problem
0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 7.9 4.0†z§ 5.2†z§ 3.2†z§ 11.0†z§¶ 7.3†z§¶
92.2 28.0 102.2 40.6 52.5 25.3
6 6 6 6 6 6
7.8 3.2 5.7 6.3 8.3 5.9
89.0 24.9 95.4 46.7 53.9 32.5
6 6 6 6 6 6
7.4†z§k 2.9†z§ 4.0†z§ 5.9†z§k 9.2 6.2†z§
This study was undertaken to compare the effects of NRT and AIT on serum cytokine concentrations, insulin resistance, and functional capacity in sedentary and men who are obese. Participants first were matched by age and percent body fat, then randomly assigned to one of the 3 groups, namely, NRT group, AIT group, and control group. To examine a long-term training scenario, we used a period of 12 weeks of training programs under carefully monitored conditions. The volume of training was matched by calorie expenditure using a heart rate monitor (Polar RCX 5 sd Run; Electro Inc., NY, USA), to make sure identical between the 2 training programs. The algorithm used in this software for the calorie expenditure estimation is based on the type of exercise, V_ O2max, activity level, age, gender, and body mass index. However, it is not the best method of determining exercise calorie expenditure. Participants in the control group continued their normal sedentary life. Basal blood samples were collected to determine serum IL-10, IL-20, TNF-a, glucose, and insulin concentrations before and after the 12 weeks of intervention period. Also, the participants were asked to consume a similar diet for at least 48 hours before blood sampling at baseline and after the training period. Subjects *i = intervention; t = time. Data are reported as mean 6 SD. †Significant difference within group (p # 0.05). zSignificant difference between groups (p # 0.05). §Control. ¶Aerobic interval training. kNonlinear resistance training.
6 6 6 6 6 6 Body mass (kg) Fat mass (kg) Waist circumference (cm) V_ O2 max (ml$kg21$min21) 1RM bench press (kg) 1RM knee extension (kg)
94.8 28.2 101.8 41.6 53.9 27.9
Before Variables
5.8 2.6 6.4 4.9 11.3 6.2
95.2 28.7 101.2 41.1 50.5 28.5
6 6 6 6 6 6
5.8 3.0 5.0 4.7 8.3 6.1
88.3 26.5 99.0 42.7 46.7 23.7
6 6 6 6 6 6
7.9 4.3 4.9 4.9 12.0 4.0
87.5 24.0 93.8 45.1 74.5 47.3
6 6 6 6 6 6
Before After Before After
the
inflammatory biomarkers, but it is still not clear what type of training is most appropriate. Therefore, the present study was designed to determine and compare the effects of 2 different 12-week exercise training interventions (NRT and AIT) on maximal oxygen uptake, fat mass, waist circumference, selected serum cytokines (TNF-a, IL-10, and IL-20) and insulin resistance in men who are obese.
0.089 0.099 0.082 0.468 0.216 0.018
i3t t After
i
p Aerobic interval training Nonlinear resistance training Control
TABLE 3. Physiological characteristic changes of the participants before and after 12 weeks of aerobic interval training, nonlinear resistance training, and control condition.*
Exercise Training and the IL-10:TNF-a Ratio
Thirty-four otherwise healthy men who are obese (age range, 34–46 years) were randomly assigned to an NRT (age, 40.4 6 5.2 years; n = 12), AIT (age, 39.6 6 3.7 years; n = 12), or CON (age, 38.9 6 4.1 years; n = 10) group. The inclusion criteria were as follows: nonsmokers, no regular exercise for at least the past 6 months, no regular consumption of medication, obese (percent body fat . 25) (19), and no history of any kind of medical condition that would prevent them from participating in the exercise intervention. The experimental protocol was approved by the Research Ethics Committee at the Islamic Azad University, Central Tehran Branch, Tehran, Iran. The risks of the study were explained to the participants before participation, and each participant signed an institutionally approved informed consent document before participation in the investigation. Procedures
All participants were asked to complete a personal health and medical history questionnaire, which served as a screening tool. Participants were familiarized with all testing procedures before the start of the testing. A maximal oxygen uptake (V_ O2max) test, maximal strength and body
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0.650 0.014 0.006 0.084 0.256 0.137 0.020 0.078 0.001 0.001 0.041 0.011 0.025 0.005 0.140 0.012 0.003 0.655 0.134 0.835 0.967 6 6 6 6 6 6 6 *i = intervention; t = time; HOMA-IR = homeostasis model assessment of insulin resistance. Data are reported as mean 6 SD. †Significant difference within group (p # 0.05). zSignificant difference between groups (p # 0.05). §Control.
5.36 3.61 0.84 7.32 20.78 2.60 2.95 0.04 1.72 0.44 0.82 3.21 0.64 0.59 6 6 6 6 6 6 6 5.62 5.52 1.39 6.68 19.33 2.99 2.33 0.07 0.92†z§ 0.27†z§ 0.64† 2.04† 0.53† 0.62† 6 6 6 6 6 6 6 6 6 6 6 6 6 6 5.92 6.60 1.72 7.31 18.66 2.90 2.66
0.05 1.86 0.42 1.06 1.09 0.74 0.75
5.81 6.20 1.62 7.17 19.23 2.96 2.52 6 6 6 6 6 6 6 Glucose (mmol$L21) Insulin (mU$ml21) HOMA-IR IL-10 (pg$ml21) IL-20 (pg$ml21) TNF-a (pg$ml21) IL10:TNF-a (ratio)
0.09 2.64 0.56 0.81 4.07 0.64 0.65
6.21 5.80 1.49 7.06 19.36 3.00 2.40
0.04 1.58 0.47 0.71 2.55 0.46 0.48
5.63 3.66 0.84 7.46 22.55 2.66 2.90 6 6 6 6 6 6 6
Before After Before After Before Variables
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composition assessments, measurement of serum cytokine levels (IL-10, IL-20, and TNF-a), and insulin resistance index were performed before and after the 12 weeks of training period.
0.03 1.48†z§ 0.34†z§ 0.99† 3.34 0.54† 0.84†z§
t i After
i3t p Aerobic interval training Nonlinear resistance training Control
TABLE 4. Serum cytokines levels and insulin resistance changes before and after 12 weeks of aerobic interval training, nonlinear resistance training, and control condition.*
Journal of Strength and Conditioning Research
Maximal Strength and V_ O2max Assessments. After familiarization, participants were asked to report to the laboratory for an additional test session designed to determine 1 repetition maximum (1RM) for the bench press and knee extension. After the warm-up, participants performed the 1RM test using the Brzycki method (28). The warm-up consisted of riding a stationary bicycle for 10 minutes, 2 sets of progressive resistance exercises similar to the actual exercises used in the main experiment, and 3 minutes of rest accompanied by some light stretching exercises. V_ O2max was estimated using the Bruce treadmill protocol (5) 2 days after the maximum strength tests. Anthropometric. Each participant’s body mass was measured while they were wearing underclothes on a balance scale (Seca, 700 Mechanical Column Scales, United Kingdom) calibrated to the nearest 0.1 kg after a 12-hour fast. Each participant’s waist circumference was measured midway between the lowest rib and the iliac crest. Subcutaneous skinfold thickness was measured sequentially, in triplicate, at the chest, abdomen, and thigh using a skinfold caliper (Lange; Country Technology, Gays Mills, WI, USA) and standard technique. The average of 3 measures for each skinfold was used. Percent body fat was estimated using the equation of Jackson and Pollock (22). Then, fat mass was estimated (body mass 3 percent body fat) (28). The same investigator performed all skinfold and girth measurements assessments. Blood Sampling. Blood samples (approximately 10 ml) were obtained from the antecubital vein in the morning (6:00 to 8:00 hours), after a 12-hour overnight fast before and after the training period. Before blood sampling, volunteers were asked to avoid from strenuous physical activity for at least 4 days. Participants were also asked whether they had experienced any symptoms of illness in the past 4 days or had taken any medication in this period. If a participant indicated that this was the case, a new appointment was made 4 days later. Posttraining blood samples from participants in the training groups were obtained 4 days after their last exercise session. Whole blood was centrifuged at 3,000 rpm (48 C) for 15 minutes, and the serum was removed and stored at 2808 C until subsequent analysis. Biochemical Analyses
Cytokines Analysis. The concentrations of IL-10, IL-20, and TNF-a were measured in serum samples in duplicate by enzyme linked immunosorbent assay (ELISA), according to the specifications of the manufacturer (Quantikine High Sensitivity Kit; R&D Systems, Minneapolis, MN, USA). The intraassay and interassay coefficients of variation were 5.0 and 7.3% VOLUME 28 | NUMBER 9 | SEPTEMBER 2014 |
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Exercise Training and the IL-10:TNF-a Ratio 80–90% of maximal heart rate with 3-minute recovery intervals at 55–65% of maximal heart rate, 3 days per week, for 12 weeks. Each training session was started with a general warm-up and finished with a cooldown. The exercise intensity was controlled by the authors, using a heart rate monitor (Polar RCX5sd Run), who ensured the correct exercise heart rates throughout the trial. The training sessions were performed in the university laboratory and were supervised by the researchers. Statistical Analyses
All data analyses were performed using SPSS 16.0 (SPSS, Inc., Chicago, IL, USA). Values are expressed as mean 6 SD. Normality of distribution was tested using the Shapiro–Wilk test. A 2-factor repeatedmeasures analysis of variance Figure 1. Percent changes in cytokines and insulin resistance after 12 weeks of aerobic interval training, nonlinear resistance training, and control condition. #Significant difference between group (P # 0.05). c, control group. (ANOVA) was used to determine the differences between interventions and across time. for IL-10, 6.2 and 9.0% for IL-20, 4.3 and 7.3% for TNF-a, The first factor was “intervention” (between-group factor) respectively. and had 3 levels (AIT, NRT, and CON), and the second factor was “time” (repeated-measures factor) and had 2 levels Insulin Resistance Assay. Serum glucose concentration was (before and after 12 weeks). When the ANOVA detected measured using the glucose oxidase method (glucose B-test; significant interactions among means (intervention 3 time), Wako Pure Chemical, Osaka, Japan). The serum insulin the Bonferroni analysis was used post hoc to identify where concentration was determined in duplicate by ELISA (Q-1 those differences occurred. Statistical power calculations for DIAPLUS kit; DIAPLUS Inc., NY, USA). Both the intrathis study ranged from 0.72 to 0.85. The level of significance assay and interassay coefficients of variation was 5.1%. was set at p # 0.05 for all statistical comparisons. Before and after the intervention, insulin resistance in the fasting state was determined using a homeostasis model RESULTS assessment (HOMA-IR) and was calculated from fasting Participant Physiological Characteristics insulin (IF) and fasting glucose (GF) as follows: HOMA-IR = Physiological characteristics of the participants at baseline (IF 3 GF)/22.5 (1). The units for IF and GF were microunits and after 12 weeks of training are presented in Table 3. After per milliliter and millimoles per liter, respectively. the training period, significant differences in body mass, fat Training Programs mass, waist circumference, V_ O2max, bench press, and knee Nonlinear Resistance Training. The NRT was with emphasis extension maximal strength were detected by ANOVA (all on endurance and general preparation and consisted of 40– p # 0.05). Post hoc tests demonstrated that significant de65 minutes of weight training per day, 3 days per week, for creases were found in the fat mass and waist circumference 12 weeks at different intensities. This training has already for both the experimental groups compared with the CON been proposed by Kraemer and Fleck (28) and the details (all p , 0.01), but no significant difference between the are shown in Tables 1 and 2. both training groups (both p . 0.05). Body mass loss was greater for the AIT group compared with other groups (both p , 0.01). There was significant increases in V_ O2max Aerobic Interval Training. The AIT consisted of running on for both training groups compared with the CON group a treadmill, consisting of 4 sets of 4 minutes at an intensity of
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Journal of Strength and Conditioning Research (both p , 0.01), but the increase was significantly higher with AIT than with NRT (p = 0.001). Maximal strength for bench press and knee extension were significantly increased with NRT compared with other groups (all p , 0.001) and with AIT compared with the CON for knee extension only (p = 0.001). However, after the intervention period, there was no improvement in these variables for the CON. Cytokines and Insulin Resistance
Serum cytokines, insulin, and glucose concentrations of the participants at baseline and after 12 weeks of training are presented in Table 4. There was no significant difference found between the conditions for glucose (Table 4). However, there were significant differences in fasting insulin levels and HOMA-IR detected by ANOVA. Post hoc tests showed that significant decreases in these variables for both the experimental groups (all p # 0.05) compared with the CON, although changes in fasting insulin levels and HOMA-IR were not significantly different between the 2 training groups. There were no significant differences found between the conditions for IL-10, IL-20, and TNF-a by ANOVA (Table 4). There were significant main effects of time (p # 0.05, Table 4), and post hoc paired t-test demonstrated a significant increase in IL-10 (AIT: 10.2%; p = 0.02 and NRT: 6.1%; p = 0.04), decrease in TNF-a (AIT: 11.9%; p = 0.01 and NRT: 10.7%; p = 0.04) after 12 weeks in both training, and increase in IL-20 only with NRT (17.8%; p = 0.001) (Figure 1). There was a significant intervention 3 time interaction for IL-10: TNF-a ratio (p = 0.020; Table 4), and post hoc analysis showed that the ratio in AIT was greater than that in the CON condition after 12 weeks (p = 0.02), but NRT tended to increase (p = 0.07). The ratio was significantly increased in NRT compared with the pretest (p = 0.01). However, after the intervention period, there was no change in these variables for the CON.
DISCUSSION This is the first study to compare the effects of NRT and AIT on inflammatory markers in sedentary men who are obese. In this study, the NRT and AIT programs (with similar calorie expenditure) were equally effective at reducing insulin resistance, fasting insulin levels, fat mass, and waist circumference. There were no significant changes in serum IL-10, IL-20, and TNF-a levels after 12 weeks of NRT and AIT, but the serum IL-10:TNF-a ratio was significantly increased with AIT when compared with the control condition. The positive effects of NRT in this study were demonstrated by a significant increase in muscular strength (as measured by bench press and knee extension 1RM). This improvement in muscular strength with NRT was accompanied by an improvement in V_ O2max and reductions in fat mass and waist circumference. We found a 6.3% improvement in V_ O2max after NRT, which supports the finding of
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Gettman and Pollack (15). They reported that shortduration (8–20 weeks) weight training increased V_ O2max by 4 and 8% in men and women, respectively. In the present study, 12 weeks of NRT and AIT decreased insulin resistance by 48.5 and 40.8%, respectively (Figure 1). These results support the findings of previous studies that reported reductions in insulin resistance after 12 weeks of endurance and RT in sedentary men who are obese (1) and in young recreationally active adult men and women, after a 6week period of aerobic training (18). Several mechanisms have been suggested to be responsible for the decreases in insulin resistance after exercise training, including increased postreceptor insulin signaling (10), increased glucose transporter protein and messenger RNA synthesis (11), and increased activity of glycogen synthase and hexokinase (13). The mechanisms responsible for the effect of RT on glucose homeostasis and insulin resistance are similar to those associated with the adaptation to aerobic exercise training (7). However, the mechanism responsible for the decreases in insulin resistance after training cannot be established from the present study. Although insulin resistance was improved with decreases in fat mass and waist circumference in the experimental groups, changes in insulin resistance were independent of changes in body composition (data not shown), as reported by others (12,39). This suggests that RT and endurance training decrease insulin resistance independent of the alterations in body composition. Twelve weeks of NRT and AIT did not significantly change serum IL-10 and TNF-a levels when compared with the control group. These results were consistent with previous studies, indicating no significant change in TNF-a after 16 weeks of endurance, resistance, and concurrent training in sedentary middle-aged healthy men (31,32). In contrast, some other studies showed that the levels of TNF-a were significantly lower after 12 weeks of exercise training when adjusting for baseline levels (20). For example, Kohut et al. (27) reported a significant reduction in this cytokine after 10 months of aerobic exercise training in older adults. A few studies on exercise training that have investigated changes in IL-10 have also reported conflicting results. Cheema et al. (8) suggested that 12 weeks of RT does not increase circulating IL-10 in kidney patients, whereas Kadoglou et al. (24) reported that plasma levels of IL-10 increased in response to 6 months of aerobic exercise training in overweight patients with type 2 diabetes mellitus. For the most part, intervention studies in participants with elevated inflammation as a result of chronic disease or obesity showed a favorable exercise training effect on specific inflammatory biomarkers. For example, in patients with coronary heart disease participating in cardiac rehabilitation, 12 weeks of aerobic exercise training resulted in increases in IL-10 (16). Similarly, 12 weeks of aerobic exercise training reduced TNF-a levels in patients with chronic heart failure (30). Recently, Santos et al. (41) reported that the levels of TNF-a and the ratio of TNF-a to IL-10 were decreased, whereas IL-10 levels VOLUME 28 | NUMBER 9 | SEPTEMBER 2014 |
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Exercise Training and the IL-10:TNF-a Ratio increased after moderate exercise training in sedentary healthy elderly men. These discrepant results may be attributed to diversity in the initial values of cytokines, differences in the timing of blood sampling, variation in the exercise protocols, and differences in subject populations. It seems that long-duration (more than 6 months) exercise training has more potential to decrease inflammation. Also, it is possible that a reduced proinflammatory cytokine response to exercise training is easier to achieve in elderly people and patients compared with healthy young individuals. Factors such as aging and the most important cardiovascular disease and type 2 diabetes mellitus have increased the levels of these inflammatory markers. Therefore, it is possible that regular exercise training is most effective at reducing the levels of these inflammatory markers in individuals with elevated levels to begin with. In addition, the results of randomized controlled trials have shown that chronic exercise training can reduce inflammation in people with higher baseline levels and those who exhibited weight loss after exercise training, whereas high levels of physical activity have little or no effect on inflammatory markers in healthy subjects (4). Further studies are needed to understand the anti-inflammatory effects of exercise training. It has been adopted that the IL-10:TNF-a ratio is an indicator of inflammatory status and disease-associated morbidity, with lower values being related to poorer prognosis. We demonstrated that even in healthy men who are obese, the AIT is able to increase the IL-10:TNF-a ratio compared with the CON (Figure 1). These finding suggest that the antiinflammatory effects of AIT are greater than those of NRT. The increase in the IL-10:TNF-a ratio with AIT may be attributed to the high intensity of training in this group. Peake et al. (37) reported that higher exercise intensity has a greater effect on IL-10 and IL-1ra responses to downhill running in well-trained runners. As an explanation of their findings, the authors suggest that higher exercise intensity could increase stress hormones and IL-6, leading to higher antiinflammatory cytokine responses (37). The mechanism responsible for the effects of the AIT on the levels of IL-10: TNF-a ratio in this study might be because of the reduction in body mass or an increase in V_ O2max or a combination of both in this training group. Studies report that an inverse relationship exists between biomarkers of inflammation and direct measurement of V_ O2max assessed during an exercise test (23,29). In this study, V_ O2max was significantly increased in both AIT and NRT (albeit less in NRT), but the IL-10: TNF-a ratio was significantly increased only in AIT. Thus, it can be suggested that perhaps a greater increase in V_ O2max with NRT (equal to AIT) can lead to similar effects. After the training period, there was no difference between training and control groups for IL-20 (further highlighted by the lack of difference between groups in percentage change shown in Figure 1). A significant decrease in circulating IL-20 levels from 152 (range, 112–184 pg$ml21) to 134 (range, 125–153 pg$ml21) pg$ml21 was observed after a 6-month
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diet-induced weight loss program in obese women (33). As an explanation for this result, we suggest that baseline levels of data should be considered because the initial level of serum IL-20 levels in the present study was 19.3 6 3.2 pg$ml21, which is less than the values reported in the study of Maiorino et al. (33). In addition, these conflicting results may be the results of differences in the type of intervention (exercise vs. diet) and differences in participants (men vs. women). Also, in this study, it was found that the initial concentrations of these cytokines is within the normal range based on the values defined by the manufacturer Kits with nonobese and healthy individuals. Thus, it seems that regular exercise training has less potential to significant changes in the normal concentration of these cytokines. A limitation of the present study is that other cytokines and inflammatory biomarkers, such as adiponectin, C-reactive protein, and IL-6, were not measured because it is possible that the NRT or AIT may have improved the activity of these. Hence, future studies should further investigate this issue.
PRACTICAL APPLICATIONS In summary, despite improvements in insulin resistance, fat _ O2max, 12 weeks of AIT and mass, waist circumference, and V NRT had no effect on serum IL-10, IL-20, and TNF-a levels. However, the serum IL-10:TNF-a ratio was increased after AIT compared with the control group. It seems that the antiinflammatory effect (for this measure at least) of AIT is better than that of NRT in otherwise healthy men who are obese. _ O2max This improvement is probably because of the higher V and lower body mass after the AIT. Collectively, these data suggest that the AIT could be a good therapy to reduce risk factors associated with type 2 diabetes mellitus and cardiovascular diseases in middle-aged men who are obese through the modification of the serum IL-10:TNF-a ratio. Also, it seems like both types of training are beneficial overall (e.g., all improvements listed above), but AIT is the only one that had some effects on one (but not all) of the anti-inflammatory markers. These findings do not support the idea that an NRT regimen with emphasis on endurance and general preparation decreases systemic inflammation in healthy middleaged men who are obese. We recommend that this issue be investigated further in future studies.
ACKNOWLEDGMENTS The authors wish to thank the volunteers for their enthusiastic participation in this study and also would like to thank Prof. Michael Gleeson and Dr. Glen Davison for reading the manuscript.
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