The beneficial effects of endurance exercise on cardiovascular health are well documented (17). Individuals who routinely engage in endurance activities (i.e., running) have increased insulin sensitivity, augmented HDL cholesterol levels, and decreased triglyceride concentrations (17). The effects of resistance exercise on vascular health, however, are less certain. Habitual strength training has been shown to favorably alter lipid and carbohydrate metabolism in a way that is protective against CHD (23). In contrast, acute resistance training (i.e., single weight training session) can invoke large increases in arterial pressure that may induce inflammation and vascular damage (14,18). These increases in arterial pressure could lead to abnormal endothelial function marked by reduced vasodilation to increased blood flow (endothelium-dependent flow-mediated dilation; FMD) (9). Decreased FMD is an early hallmark of CHD and is a strong predictor of future vascular events (12). Interestingly, this impairment in endothelial function after a single weight training session occurs only in sedentary individuals and not in trained athletes (14).
Key mediators that may link active lifestyles to improved vascular function are adipose tissue-derived hormones. Adiponectin is a hormone released almost exclusively from adipose tissue that exerts cardioprotective effects and is inversely related to body mass index (BMI) (10). Recent studies indicate that adiponectin protects endothelial function by enhancing production of nitric oxide (NO) in endothelial cells and by decreasing cytokine production from macrophages (10,15). Leptin and resistin, in contrast, are proatherogenic hormones derived from adipocytes that are positively correlated to percent fat mass and waist circumference (20). Leptin receptors are expressed in primary cultures of human endothelial cells, and bioassays have revealed that this hormone demonstrates angiogenic activity (22). As for resistin, recent evidence suggests that this mediator causes endothelial dysfunction by promoting oxidative stress and by down-regulating the production of NO (5,8). The ability of a single weight training session to beneficially modulate adipokine profile in a way that protects against endothelial function has yet to be tested. Moreover, whether these effects differ in trained versus untrained subjects also remains unknown.
Therefore, this study tested the hypothesis that acute resistance training would beneficially modulate adipokine profile (i.e., increase adiponectin and decrease leptin and resistin) in trained individuals but not in sedentary subjects. Furthermore, we hypothesized that these alterations in adipokines in trained individuals would be associated with improved vascular function (i.e., increased FMD) during acute exertion.
Subjects and group assignment.
Male subjects (n = 43) were recruited by advertisements placed in newspapers and community centers. Potential subjects were screened by a medical history questionnaire and a physical examination. Key inclusion criteria were as follows: male, aged 20-40 yr, nonsmoking, free of cardiovascular disease, nondiabetic, BMI between 18.5 and 29.9 kg·m−2, not taking lipid or glucose lowering medications, not taking fish oil supplements, not taking protein (e.g., whey protein) supplements, normotensive- or hypertensive-controlled, and free of other medical conditions that would preclude subjects from participating in an acute weight training session. Women were excluded from participating in the study to avoid the confounding effects of menstrual cycle on FMD (11). Eligible subjects were grouped according to training status (i.e., exercise history) as follows: 1) sedentary (no participation in an exercise program for 12 months before the beginning of the study); 2) conditioned weight trainers (weight training for at least 1 h, three times per week, for 6 months before the study); 3) runners (running at least 15 miles·wk−1 for 6 months before the study); and 4) both weight trainer + runner (weight training for at least 1 h, three times per week, and running 15 miles·wk−1 for 6 months before the study). Nutritional habits of the participants were assessed by a 24-h recall taken the day before the intervention by a registered dietician. Nutrient distribution was analyzed using the Nutrition Data System (NDS, Nutrition Coordinating Center, University of Minnesota). The protocol was approved by the Office for the Protection of Research Subjects at the University of Illinois at Chicago. Before the commencement of the trial, all volunteers gave their written informed consent to participate in the study.
Acute weight training protocol.
The acute resistance training session was performed using a plate-loaded leg press machine (Nautilus XP Plate-loaded Leg Press; Nautilus Inc., Houston, TX). The exercise session was designed to elicit an equivalent blood pressure response between groups with a bilateral leg press thereby limiting differences in blood pressure responses, a key determinant of the cardiovascular response to exercise and a potential confounder of adipokine release between athletic populations. All subjects were fasted (12 h) and asked to refrain from exercise (24 h) before the intervention. All participants performed the acute weight training session between 8:00 and 11:00 a.m. to alleviate the effects of diurnal variations on circulating adipokine concentrations (7). Briefly, subjects sat in the machine with legs superior at approximately a 30° hip angle. Participants who were familiar with the machine (i.e., conditioned weight trainer group and weight trainer + runner group) warmed up using a low weight (approximately 30%-40% reported 1-repetition maximum) for two sets of 8-12 repetitions each and then attempted near-maximal exertion for four more sets of 8-12 repetitions each. Subjects who were not familiar with the machine (i.e., sedentary group and the runner group) warmed up using minimum resistance (two to three plates) for two sets of 8-12 repetitions and then attempted near-maximal exertion for four more sets of 8-12 repetitions each. A 2-min rest interval was allotted between each set, and an isometric hold was performed during the last repetition of each set for blood pressure determination. Weight was subsequently added as tolerated, and the maximum weight lifted was determined by the subject with a total exercise duration of approximately 15 min for each participant.
Body weight was assessed without shoes and in light clothing before the commencement of the acute weight training session. Height was measured using a wall-mounted stadiometer. BMI was calculated as kilograms per squared meter (kg·m−2). Waist circumference was measured midway between the lowest rib and the iliac crest. Percent body fat and fat-free mass were evaluated before the weight training session using dual-energy x-ray absorptiometry (DXA; Model DPXC; Lunar Corp., Madison, WI).
Plasma volume change assessment.
Plasma volume change was determined after exercise from hemoglobin and hematocrit concentrations using the following equation (6):
where "Hb" and "Hct" are hemoglobin and hematocrit values, respectively, before "B" or after "A" the acute exercise session. Hematocrit was determined by the microcapillary tube method (6). Hemoglobin concentration was determined with the Hb Pro hemoglobin analyzer (International Technidyne Corp., Edison, NJ).
Twelve-hour fasting blood samples were collected before and immediately after each weight training session. Blood was centrifuged for 15 min at 520g and 4°C to separate plasma from red blood cell, and was stored at −80°C until analyzed. Circulating concentrations of adiponectin, leptin, and resistin were measured by ELISA (R&D Systems, Inc., Minneapolis, MN), according to the manufacturer's instructions. The intra-assay variances were 3.8% for adiponectin, 3.2% for leptin, and 2.7% for resistin.
Brachial artery measurements of FMD.
Brachial artery FMD was assessed immediately before the intervention and within 15 min after the exercise session. Ultrasound imaging of the brachial artery (Logiq 500 Pro Ultrasound System; General Electric Company, Schenectady, NY) was performed in a longitudinal plane at a site 1-3 cm proximal to the antecubital fossa, with the arm abducted approximately 80° from the body and the forearm supinated. The ultrasound probe (11 MHz) was positioned to visualize the anterior and posterior lumen-intima interfaces to measure diameter or central flow velocity (pulsed Doppler). The probe site was marked for accurate repositioning after exercise. After baseline images were recorded, a blood pressure cuff on the forearm was inflated to 200 mm Hg for 5 min. To assess FMD, 10 s of images were captured at a rate of 10 images per second, 30 s, 1 min, and 2 min after cuff release. This process was repeated immediately after resistance exercise with the same transducer placement. Images were digitally recorded using Brachial Imager (Medical Imaging, Iowa City, IA) at 10 frames per second for 10 s at each time period. Brachial artery diameter was measured from the intimal medial border interface on each frame using the average of 100 distinct evenly spaced longitudinal diameters for each measurement using an automated edge-detection algorithm. The minimum (diastolic) diameters were determined for each cardiac cycle, and these minimum diameters (n = 8-10) were then averaged to obtain one brachial artery diameter at each time point. Percent FMD was calculated using the averaged minimum mean brachial artery diameter at baseline compared with the largest mean values obtained after either release of the forearm occlusion. Percent FMD was calculated using the averaged minimum mean brachial artery diameter at baseline compared with the largest mean values obtained after release of the forearm occlusion.
Plasma CHD risk factors.
Total cholesterol, direct LDL cholesterol, HDL cholesterol, and triglyceride concentrations were measured using enzymatic kits (Roche Diagnostics, Indianapolis, IN). The intra-assay variances for total cholesterol, direct LDL cholesterol, HDL cholesterol, and triglyceride were 4.2%, 3.9%, 2.5%, and 1.9%, respectively. C-reactive protein (CRP) was measured by ELISA, (R&D Systems, Inc.), with an intra-assay variance of 2.3%.
Results are presented as means ± SEM. All data were tested for normal distribution with the Shapiro-Wilk test for normality. ANOVA was used to evaluate differences for each variable between groups at baseline (before the acute weight training session) and after weight training. Post hoc comparisons between groups were performed using Tukey test. Paired-samples t-tests were used to determine whether statistically significant within-group differences existed for adipokine concentrations, FMD values, and CHD risk parameters before and after the weight training session. Pearson correlations were used to evaluate how adipokine concentrations relate to anthropometric, FMD, and CHD risk parameters. A level of statistical significance at P < 0.05 was used in all analyses. Data were analyzed using SPSS software (version 17.0; SPSS Inc., Chicago, IL).
Subject diet and anthropometric measures.
A total of 43 males were recruited to participate in the study. The number of participants in each group was as follows: n = 10 sedentary, n = 10 conditioned weight trainers, n = 12 runners, and n = 11 conditioned weight trainer + runners. There were no differences in mean energy intake (day before the acute intervention) between the sedentary (2932 ± 86 kcal), conditioned weight trainer (2800 ± 133 kcal), runner (3102 ± 140 kcal), and conditioned weight trainer + runner groups (2945 ± 80 kcal). Total fat and protein intake also did not differ between sedentary (113 ± 4 g; 117 ± 4 g), conditioned weight trainer (102 ± 4 g; 103 ± 3 g), runner (120 ± 5 g; 123 ± 3 g), and conditioned weight trainer + runner groups (108 ± 3 g; 118 ± 5 g). Anthropometric characteristics of the subjects are presented in Table 1. There were no differences between groups for age, body weight, height, BMI, waist circumference, percent body fat, or fat-free mass. Subjects in each group were healthy, young (26-28 yr), lean (waist circumference, 79-81 cm; percent body fat, 17%-22%) males.
Plasma volume change after acute weight training.
Changes in plasma volume, along with hematocrit and hemoglobin values, are presented in Table 2. Immediately after the exercise, there was a decrease in plasma volume in all groups (−17.7 ± 0.3). There were no significant differences between groups for plasma volume, hematocrit, or hemoglobin.
Plasma adipokines at baseline in sedentary versus trained men.
Circulating adipokine concentrations in each group are displayed in Figure 1. Levels of the proatherogenic hormone, leptin, were approximately 50% lower (P < 0.05) in all trained groups (conditioned weight trainers, runners, or conditioned weight trainer + runners) when compared with the sedentary group at baseline. Lower leptin levels at baseline in all trained groups were related to smaller waist circumference (r = 0.71, P = 0.02) and lower percent body fat (r = 0.81, P = 0.005). In contrast, there were no differences in circulating levels of adiponectin and resistin between sedentary and trained individuals at baseline. Moreover, adiponectin and resistin were not correlated to any of the tested body composition parameters in the sedentary or trained groups at baseline.
Changes in plasma adipokines after acute weight training.
Levels of the cardioprotective hormone, adiponectin, increased (P < 0.05) by 30 ± 7% and 37 ± 9% in response to acute weight training in the conditioned weight trainer group and in the weight trainer + runner group, respectively (Fig. 1). These increases in adiponectin were not observed in the sedentary group or runner group after training. Similarly, plasma resistin concentrations decreased (P < 0.05) by 35 ± 9% and 34 ± 8% in the weight trainers and weight trainer + runners, respectively, after the acute weight training. These beneficial modulations in resistin were not noted in either the sedentary or the runner group in response to weight training. Leptin levels were not affected by the acute weight training session for any group.
Relationship between plasma adipokines and brachial FMD.
At baseline, brachial artery FMD was similar between sedentary individuals (6.7 ± 0.6%), weight trainers (5.7 ± 0.9%), runners (5.7 ± 0.5%), and weight trainer + runners (4.7 ± 0.5%). Likewise, immediately after the training session (i.e., measurement taken within 15 min), FMD values did not differ between exercise groups (5.6 ± 0.4%), weight trainers (7.6 ± 0.8%), runners (8.1 ± 0.7%), and weight trainer + runners (5.7 ± 0.9%). However, when postintervention values were compared with baseline, brachial artery FMD was shown to be impaired (P < 0.05) in the sedentary group (i.e., decrease in FMD of 1.1 ± 0.3%). No such impairments were noted in the trained groups, as FMD increased (P < 0.05) by 1.9 ± 0.6%, 2.4 ± 0.4%, and 1.5 ± 0.7% in the weight trainers, runners, and weight trainer + runners, respectively, after the intervention. Improvements in FMD were related to increases in adiponectin (r = 0.61, P = 0.01) and decreases in resistin (r = −0.56, P = 0.01) in the weight trainers and weight trainer + runner groups only.
Changes in CHD risk after acute weight training and relation to plasma adipokines.
The effects of acute weight training on key CHD risk parameters are displayed in Table 3. There were no differences at baseline between groups for total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, CRP concentrations, and systolic or diastolic blood pressure. Moreover, there were no differences after intervention between groups for these variables. Likewise, vascular disease risk indicators did not change as a result of the acute weight training intervention within group (comparing before to after values). In the conditioned weight training group and the weight trainer + runner group, increased adiponectin was related to higher levels of HDL cholesterol after intervention (r = 0.71, P = 0.001). In these two groups, it was also observed that decreased resistin concentrations were related to the slight declines in triglyceride levels after resistance training (r = 0.73, P = 0.03). These relationships between adipokines and lipid levels were not demonstrated in the sedentary and runner groups. Postintervention leptin levels were not related to any CHD risk parameter for any group.
This study tested the hypothesis that a single weight training session would beneficially modulate adipokine profile in a way that would exert protection against endothelial dysfunction in trained but not sedentary subjects. Results reveal that acute strength training increased levels of adiponectin while concomitantly lowering levels of resistin but only in those who were habitual weight trainers (weight trainers and weight trainer + runner groups). These beneficial adipokine modulations did not occur in runners or sedentary individuals. In addition, these increases in adiponectin, and decreases in resistin, were associated with improvements in FMD in habitual weight trainers but not in sedentary subjects or runners. Leptin levels showed no response to acute weight training for any group and were not related to changes in FMD.
The role of exercise in modulating adiponectin.
Adiponectin is secreted almost exclusively from adipose tissue (10) and plays a protective role against the development of CHD by inhibiting monocyte adhesion to endothelial cells and macrophage-to-foam-cell formation in vitro (10,15). Circulating levels of adiponectin have been shown to increase with weight loss and be negatively correlated to increases in BMI and waist-hip circumference (10). As such, lifestyle interventions that induce weight loss, such as diet and exercise programs, are often implemented to increase circulating levels of this cardioprotective adipokine (3,10). In the present study, we demonstrate that adiponectin is very responsive to acute strength training (30%-37% increases from baseline) but only in those who habitually lift weights (weight trainer and weight trainer + runner groups). We also show that these increases in adiponectin may protect habitual weight trainers from the endothelial dysfunction that occurs with acute exertion (i.e., increased adiponectin was associated with augmented FMD). Although the possible mechanisms linking adiponectin to improved endothelial function are still not clear, we speculate that modulations in NO by adiponectin may be involved. Nitric oxide, released from the endothelium, is important in regulating vascular tone, inhibiting platelet aggregation, and suppressing smooth muscle cell proliferation (4). Plasma adiponectin stimulates the release of NO resulting in endothelial vasodilation. Thus, individuals who routinely engage in resistance exercise may have higher adiponectin with enhanced endothelial function. Nevertheless, it is still unclear why these beneficial shifts in adiponectin only occurred in weight trainers and not in runners. We also show here that baseline levels of adiponectin do not differ between trained or sedentary individuals matched for BMI. These findings are complementary to those of Perseghin et al. (19), who found no significant difference in plasma adiponectin between marathon runners and lean sedentary control subjects. In this study, we also examined the effect of acute exertion on other CHD risk indicators and how changes in these parameters may relate to modulations in adipokines. Results reveal that increases in adiponectin were related to higher levels of HDL after intervention. Similar relationships between adiponectin and HDL have been demonstrated after acute endurance exercise (2). Future studies in this area should investigate the time course effects of weight training on HDL in relation to changes in adiponectin. Taken together, these results suggest that a single session of weight training can induce multiple cardioprotective effects that may be mediated by elevations in adiponectin.
The role of exercise in modulating leptin.
Accumulating evidence suggests that leptin may play an important role in the development of CHD (1). Leptin exerts many atherogenic effects that oppose NO including induction of endothelial dysfunction, platelet aggregation, and proliferation of vascular smooth muscle cells (1). Thus, lifestyle interventions, such as resistance training, that decrease circulating levels of leptin are considered cardioprotective (3,20). In the present study, we demonstrate that baseline concentrations of leptin are approximately 50% lower in those subjects who routinely participate in endurance or resistance training compared with sedentary individuals. This is consistent with reports of reduced leptin in marathon runners versus sedentary individuals (19). Although we matched subjects in each group for BMI, the waist circumference and percent body fat in weight trainer, runner, and weight trainer + runner groups were smaller than those of the sedentary group. Thus, this reduced level of adiposity may explain why leptin levels were lower in trained subjects relative to the sedentary subjects. In acute resistance exercise effects, there was no change in leptin after intervention for any group. These findings are complementary to previous reports showing that leptin concentrations are not altered by acute (<60 min) endurance activity in healthy males and females (16). A reduction in fat mass by exercise is most likely required to modulate leptin levels (16). Because the acute resistance training protocol implemented in this study had no effect on fat mass, this may explain why leptin concentrations were unaltered after exercise.
The role of exercise in modulating resistin.
In humans, resistin is expressed primarily in leukocytes and adipocytes. Resistin exhibits several proatherogenic properties, such as promoting carotid wall thickness and impairing endothelium-dependent vasodilation (5,8,21). In the present study, we show that a single weight training session may decrease plasma resistin but only in those who regularly engage in strength training. We also show that these reductions in plasma resistin are related to increased brachial artery FMD. As with adiponectin, we speculate that the mechanism linking decreased resistin to increased FMD may involve changes in the production of NO (5,8). Resistin has been shown to blunt NO production (5,8). As such, it can be hypothesized that since resistin was significantly decreased after exertion, there would be less resistin in the circulation to inhibit NO. Thus, more NO may be produced, thereby allowing for an enhancement in endothelium-dependent vasodilation after intervention. The reason why this response only occurred in weight trainers, and not in runners, is not known. Recent evidence suggests that resistin is not readily affected by acute bouts (45 min) of endurance exercise (13). Coupled with the observation that adiponectin is increased after acute resistance training in conditioned weight trainers, these data may suggest a preferential effect of weight training over other modes of exercise on fat cell metabolism, skeletal muscle, and adipokines. However, further studies evaluating the relationships among exercise, adipokines, and cardiovascular health are needed.
This study has several limitations. First, blood samples were only taken directly before and after (i.e., within 15 min) the intervention. Drawing blood at 5-min intervals during and after the session would have yielded interesting data on time course changes in adipokine levels in response to weight training. Second, neither aerobic power nor energy expenditure was measured during the intervention. Because leptin levels may be affected by total exercise energy expenditure from increased metabolism during exercise (16), assessing energy expenditure may have helped to further explain our leptin data. Third, the generalizability of these findings is limited in that these effects may only occur in young, lean, males and that this adipokine response may only occur in response to this specific single progressive leg press weight training protocol.
In sum, these findings suggest that habitual resistance training may modulate adipokine profiles in a way that is protective against the endothelial dysfunction that occurs with acute exertion. These data further support the role of weight training in improving cardiovascular health. Further evaluation of resistance and endurance exercise on adipokines and the link to cardiovascular disease appears warranted.
This work was supported by the National Institutes of Health (grant no. K23HL85614, 2008). The authors thank the help of Melissa Gove during the analysis phase of the trial.
The authors have no conflicts of interest to report. The results of the present study do not constitute endorsement by the American College of Sports Medicine.
1. Beltowski J. Leptin
and atherosclerosis. Atherosclerosis
2. Bobbert T, Wegewitz U, Brechtel L, et al. Adiponectin
oligomers in human serum during acute and chronic exercise: relation to lipid metabolism and insulin sensitivity. Int J Sports Med
3. Bouassida A, Chamari K, Zaouali M, Feki Y, Zbidi A, Tabka Z. Review on leptin
responses and adaptations to acute and chronic exercise. Br J Sports Med
. 2008 Oct 16. [Epub ahead of print].
4. Chen H, Montagnani M, Funahashi T, Shimomura I, Quon MJ. Adiponectin
stimulates production of nitric oxide in vascular endothelial cells. J Biol Chem
5. Dick GM, Katz PS, Farias M 3rd, et al. Resistin
impairs endothelium-dependent dilation to bradykinin, but not acetylcholine, in the coronary circulation. Am J Physiol Heart Circ Physiol
6. Dill DB, Costill DL. Calculation of percentage changes in volumes of blood, plasma, and red cells in dehydration. J Appl Physiol
7. Gavrila A, Peng CK, Chan JL, Mietus JE, Goldberger AL, Mantzoros CS. Diurnal and ultradian dynamics of serum adiponectin
in healthy men: comparison with leptin
, circulating soluble leptin
receptor, and cortisol patterns. J Clin Endocrinol Metab
8. Gentile MT, Vecchione C, Marino G, et al. Resistin
impairs insulin-evoked vasodilation. Diabetes
9. Gokce N, Keaney JF Jr, Hunter LM, Watkins MT, Menzoian JO, Vita JA. Risk stratification for postoperative cardiovascular events via noninvasive assessment of endothelial function: a prospective study. Circulation
10. Han SH, Quon MJ, Kim JA, Koh KK. Adiponectin
and cardiovascular disease: response to therapeutic interventions. J Am Coll Cardiol
11. Hashimoto M, Akishita M, Eto M, et al. Modulation of endothelium-dependent flow-mediated dilatation of the brachial artery by sex and menstrual cycle. Circulation
12. Jambrik Z, Venneri L, Varga A, Rigo F, Borges A, Picano E. Peripheral vascular endothelial function testing for the diagnosis of coronary artery disease. Am Heart J
13. Jamurtas AZ, Theocharis V, Koukoulis G, et al. The effects of acute exercise on serum adiponectin
levels and their relation to insulin sensitivity in overweight males. Eur J Appl Physiol
14. Jurva JW, Phillips SA, Syed AQ, et al. The effect of exertional hypertension evoked by weight lifting on vascular endothelial function. J Am Coll Cardiol
15. Kobayashi H, Ouchi N, Kihara S, et al. Selective suppression of endothelial cell apoptosis by the high molecular weight form of adiponectin
. Circ Res
16. Kraemer RR, Chu H, Castracane VD. Leptin
and exercise. Exp Biol Med (Maywood)
17. Lavie CJ, Thomas RJ, Squires RW, Allison TG, Milani RV. Exercise training and cardiac rehabilitation in primary and secondary prevention of coronary heart disease. Mayo Clin Proc
18. MacDougall JD, Tuxen D, Sale DG, Moroz JR, Sutton JR. Arterial blood pressure response to heavy resistance exercise. J Appl Physiol
19. Perseghin G, Burska A, Lattuada G, et al. Increased serum resistin
in elite endurance athletes with high insulin sensitivity. Diabetologia
20. Sattar N, Wannamethee G, Sarwar N, et al. Leptin
and coronary heart disease: prospective study and systematic review. J Am Coll Cardiol
21. Shin HJ, Park S, Yoon SJ, et al. Association between serum resistin
and carotid intima media thickness in hypertension patients. Int J Cardiol
22. Sierra-Honigmann MR, Nath AK, Murakami C, et al. Biological action of leptin
as an angiogenic factor. Science
23. Williams MA, Haskell WL, Ades PA, et al. Resistance exercise in individuals with and without cardiovascular disease: 2007 update: a scientific statement from the American Heart Association Council on Clinical Cardiology and Council on Nutrition, Physical Activity, and Metabolism. Circulation