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To examine the influence of moderate-intensity (50% of VO2peak) exercise training (MI) versus high-intensity (75% of VO2peak) exercise training (HI) on regional fat distribution and plasma adiponectin, we randomized 18 overweight (body mass index [BMI]=30±1 kg/m2) elderly (71±1 years) to HI, MI, or a control group (CON). Subjects enrolled in HI or MI completed a 12-week exercise training protocol designed to expend 1000 kcal/week. Body composition testing was completed prior to and following the exercise training using dual energy X-ray absorptiometry and a computed tomography scan. Plasma adiponectin was measured using enzyme-linked immunoassay (ELISA). VO2peak improved in HI and MI, whereas there was no change in VO2peak in CON. No significant change in body weight, BMI, and % fat occurred in MI, HI, or CON. Although there was a significant reduction in visceral fat with HI (−39 cm2), there was no change in the MI or CON groups. In addition, there was a significant increase in thigh muscle attenuation in the HI group. There were no changes in thigh muscle attenuation in the MI and CON groups. Also, there was no change in plasma adiponectin in the MI, HI, or CON groups. In summary, our direct comparison of exercise intensity without weight loss promotes the efficacy of HI in the reduction in visceral fat, even without changes in adiponectin.
The increase in obesity and inactivity with advancing age are directly associated with the pathogenesis of metabolic abnormalities, including hypertension, dyslipidemia, and insulin resistance. This cluster of interrelated conditions, which increases the risk of type 2 diabetes (T2D) and cardiovascular disease (CVD), is known as the metabolic syndrome.1 Prevalence of the metabolic syndrome increases with age and exists in an alarming ~43% of people aged over 60 years.2 Therefore, from a public health standpoint, efficacious strategies must be developed to prevent and/or treat metabolic complications in our aging population.
For health promotion and disease prevention, the Centers for Disease Control and Prevention (CDC) and the American College of Sports Medicine (ACSM) have recommended 30 minutes or more of physical activity on most, preferably all, days of the week.3 In spite of favorable exercise training-induced changes in adipose tissue and glucose metabolism,4–6 training paradigms from these studies used a longer duration and/or a greater exercise intensity beyond the current recommendations for moderate-intensity exercise training.3
In an effort to define the influence of CDC/ACSM recommendations for physical activity on glucose metabolism in elderly, obese individuals, we previously compared the efficacy of 12 weeks of moderate intensity (~50% VO2peak) (MI) or high-intensity (~75% VO2peak) (HI) aerobic exercise training (matched with an equivalent caloric expenditure of 1000 kcal/week) on improvements in insulin-stimulated glucose disposal (ISGD). In these studies, MI or HI did not result in weight loss, and only HI was effective in improving ISGD, which was entirely reliant on increased nonoxidative glucose metabolism.7 Our results were also quite similar to another study comparing the role of exercise intensity in elderly, obese women.8 In addition, O'Leary et al. demonstrated a relationship between exercise training-induced reductions in visceral fat and improvements in glucose metabolism.9 However, the optimal intensity of exercise necessary to promote the reduction of visceral fat has not been evaluated in elderly, obese adults.
It is also interesting to note that excess abdominal fat is negatively associated with adiponectin levels.10 This is important because adiponectin has been shown to improve mitochondrial function11 and potentially reduce the level of insulin resistance.12 Results from exercise training studies have been largely inconclusive, with some supporting the role of exercise training in the modulation of adiponectin13–15 and others finding little evidence for a direct exercise-mediated effect.16,17 Unfortunately, the training regimens from these studies were extremely variable, had a variable influence on body weight, incorporated a wide variety of exercise intensities and modalities, and also employed a wide range of individuals.
Therefore, the purpose of our study was to determine the efficacy of MI versus HI on the reduction of regional fat depots and favorable changes in plasma adiponectin using the minimal ACSM/CDC minimal recommendations in elderly, obese adults.
Men and women aged 65–90 years were recruited from the central Arkansas area using newspaper advertisements. Subjects who reported being overweight or obese (body mass index [BMI]≥26 and <37 kg/m2), nonsmoking, sedentary (≤2 days/week of structured physical activity), weight stable (± ≤5 kg) over the past 6 months, and who were not consuming medications known to influence glucose metabolism were invited to our laboratory for a comprehensive medical screening. As part of our medical screening processing, a complete blood count, an oral glucose tolerance test (OGTT), and electrolyte panel were completed. Exclusion criteria included a creatinine >1.4, and a serum glutamate pyruvate transaminase >2 times normal. All volunteers with a resting blood pressure above 160/90 mmHg were excluded. It is important to realize that obese volunteers often had other medical conditions. Thus, it would have been impractical to exclude all patients taking medications, and we could not ethically discontinue all medications for the duration of the intervention. As a result, we permitted antidepressant selective serotonin reuptake inhibitors and estrogen replacement/oral contraceptives. Subjects that take Gemfibrozil (or other fibrates), niacin, or other pharmaceuticals that have potential effects on lipid metabolism were excluded. We excluded any patient with a chronic rheumatological inflammatory condition or a malignancy, or any patient taking corticosteroids. In addition, volunteers with a history of cardiovascular disease were excluded. Finally, any patient who had a medical condition or was taking a medication that, in the opinion of the study physician, represented an unacceptable risk, was excluded from the study. Our inclusion/exclusion criteria provided us with an opportunity to study the influence of minimal ACSM/CDC recommendations for exercise training under moderate- and high-intensity conditions in elderly, overweight participants under well-controlled conditions without the existence of cardiovascular disease, cancer, or other inflammatory diseases and without the complicating the interpretation of the data through the use of medications/supplements that would impart an independent influence on the regulation of metabolism.
Subjects with a plasma glucose concentration of 100–199 mg/dL 2 hours following the consumption of a 75-gram oral glucose load, but who were otherwise healthy, were eligible for study participation. Each subject provided written informed consent prior to screening and study participation, and all study procedures were approved by the Institutional Review Board of the University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System Research and Development Committee.
Following completion of screening visit and eligibility evaluation, subjects were randomly assigned to moderate exercise training (MI; n=6), high-intensity exercise training (HI; n=6), or a control (CON) group (n=6). To standardize dietary intake as part of the accurate assessment of peripheral insulin sensitivity (glucose metabolism data has been previously published),7 maintain body weight, and prevent differences in dietary intake, each subject was provided a mixed diet (35% fat, 20% protein, 45% carbohydrate) during 4 days of controlled feeding prior to baseline (week 2) and postintervention (week 14) testing period.18 Subjects were instructed to eat only the food prepared by our metabolic kitchen and to consume them completely.
Subjects who were randomized to one of the exercise training groups were trained 4–5 days a week for 12 weeks at either 50% (MI) or 75% (HI) of their VO2peak, and caloric expenditure was matched at 1000 kcal/week for each group. Subjects randomized to the control group completed only the screening process and the testing procedures. All subjects were trained under supervision at the Donald W. Reynolds Institute on Aging using a cycle ergometer (Model 818E, Monarch, Varberg, Sweden) as previously described.7 Nonexercising subjects were instructed to maintain their habitual physical activity.
Body mass, height, and body composition testing were measured at week 2 and week 14. Fat mass and lean tissue mass were measured by dual-energy X-ray absorptiometry using a Hologic QDR 2000 densitometer (DXA). Images from the computed tomography (CT) scans were completed using a GE High-Speed Advantage (GE Medical Systems, Milwaukee, WI) at 120 kV, 280 mA, a 512×512 matrix, and a scanning duration of 1 second. All volunteers rested for 1 hour before each scan to minimize muscle size changes due to posturally related fluid shifts.19 For the measurement of visceral adipose tissue, a lateral scout was used to identify a 10-mm scan at the L4-L5 vertebral disc space. Abdominal subcutaneous adipose tissue cross-sectional area was determined by highlighting the area between the skin and the external-most aspect of the abdominal muscle wall. A CT of the thigh was also obtained to examine changes in adipose tissue cross-sectional area. A scout image was used to acquire an orientation of skeletal muscle landmarks. Subsequently, a single 10-mm slice was obtained at a midpoint between the right iliac crest and the patella of the dominant leg. All computed tomographic images were stored on magnetic tape, transferred to a personal computer, and analyzed using medical imaging software (SliceO-Matic version 4.2; Tomovision, Montreal Quebec). The attenuation ranges were −25 to 145 Hounsfield units for muscle, −250 to −40 Hounsfield units for fat, and >150 Hounsfield units for bone. The coefficient of variation for this technique is 1.0–1.5% in our laboratory.
Fasting blood samples were collected for analysis of plasma adiponectin prior to and 48–72 hours following the last exercise training session. These blood samples were centrifuged at 4°C, and the plasma was immediately stored at −70°C. Upon completion of the study and using a single assay, all samples were measured in duplicate using enzyme-linked immunoassay (ELISA; Linco Research, Inc., St Charles, MO).
To compare changes in regional fat distribution and plasma adiponectin, a repeated-measures analysis of variance (ANOVA) was used. All data were analyzed using Prism 4 for Macintosh (GraphPad software, Inc., San Diego, CA). Data are reported as means±standard of the mean (SEM).
Eighteen elderly, obese volunteers successfully finished the entire study paradigm. The overall mean age of our volunteers for this study was 71±1 years (see Table 1 for clinical characteristics and Table 2 for a description of maximum work output for the volunteers in this study).
Although there was a significant increase in VO2peak in the HI (1.4±0.1 to 1.7±0.2 mL×kg−1×min−1) and MI (1.3±0.1 to 1.7±0.1 mL×kg−1×min−1), there was no significant change in VO2peak in the control group. Also, there was a consistent, significant increase in maximum work output in the HI (positive Δ of 38±11 watts) and MI (positive Δ of 44±14 watts) groups. Maximum work output was not increased in the control group.
While abdominal visceral fat decreased (P=0.03) in the HI group (Δ of −39±11 cm2) (Fig. 1), there was no change in abdominal visceral fat in the MI or control group. There was no change in abdominal subcutaneous fat in HI (Δ of −12±4 cm2), MI (Δ of −13±4 cm2) on the control group (Δ of +10±6 cm2). There was a trend toward reduced thigh fat in HI (Δ of −18±10 cm2), but it was not significant.
Although plasma adiponectin increased in an absolute sense in the HI (Δ of + 2.5±1.5 ng/mL) and MI (Δ of +1.6±2.2 ng/mL) groups, these changes were not significant and there was no change in plasma adiponectin in the control group (Fig. 2).
It is a generally well-accepted notion that a positive imbalance between caloric intake and caloric expenditure contributes to the development of insulin resistance.20 Also, the aging process itself may place elderly individuals at an even greater risk for metabolic abnormalities.21 This has become an especially relevant issue in our current society with the rapid growth of an aging population and the corresponding increased burden on health-care resources.22 As such, elderly individuals need definitive physical activity recommendations that are based on the results of clinical studies in the geriatric population. Therefore, we chose to evaluate the efficacy of the minimal ACSM/CDC recommendations for physical activity on factors potentially responsible for the development of insulin resistance (i.e., excess regional adipose tissue and reduced levels of plasma adiponectin). The results of our supervised exercise training studies using matched caloric expenditure of 1000 kcal/week demonstrated that only HI facilitated a reduction in visceral fat. MI resulted in no change in visceral fat. Also, MI or HI (in the absence of weight loss) had no significant influence on abdominal subcutaneous fat, thigh fat, or plasma adiponectin.
Previous studies in middle-aged individuals with T2D have demonstrated significant reductions in visceral fat and subcutaneous fat as a result of high-intensity exercise training.23,24 In these studies, the training period of 8 weeks was 33% shorter, but the relative exercise intensity and mode of exercise training (i.e., cycle ergometer) were relatively consistent with that employed in the present investigation, except for the addition of interval type exercise within the training paradigm. More specifically, these authors used high-intensity, continuous cycle ergometer training at 75% of VO2peak for 30 minutes on 2 days of the week, and an interval exercise training session consisting of five bouts at 85% VO2peak for 2 minutes separated by intermittent bouts at 50% of VO2peak for 3 minutes. Hence, using a modified interval training design in previously unfit individuals with T2D may have promoted use of fat as an energy source.25 In turn, this could have promoted a combined reduction in abdominal subcutaneous fat and visceral fat, even under conditions of relatively low caloric expenditure and no change in total body mass.
In addition to the previously mentioned studies incorporating the use of interval training, the studies by O'Leary et al. demonstrated an exercise training-induced reduction in visceral fat,9 abdominal subcutaneous fat, and total abdominal fat. In these studies, the volunteers exercised at ~70% of VO2max, 5 days of week for 50–60 minutes and lost ~7 pounds over the course of the study. As such, these results have raised an interesting question as to whether weight loss may be required to initiate a reduction in the levels of visceral fat. In studies where the influence of exercise training (with and without weight loss) were compared, exercise training with weight loss (~8 pounds) resulted in a 26% reduction in visceral fat while exercise training without weight loss (complete caloric compensation for the energy expenditure of exercise training) still promoted a 17% reduction in visceral fat.26 Although the duration of the exercise training bouts were significantly longer (~40–60 minutes per session versus ~30 minutes in our study) in this study, the intensity of the exercise training was almost identical to the HI group in our present study. Therefore, we were able to demonstrate an exercise training-induced reduction in visceral fat (~20%) at the same relative exercise intensity, even with a 20–40% reduction in total exercise training duration.
Abdominal adiposity has been suggested as a more powerful predictor of insulin resistance than fitness, especially among older individuals.27 Although visceral fat decreased in HI, the lack of a change in abdominal subcutaneous fat in either exercise training group may be linked to a negligible or nonexistent change in adiponectin, due to the strong relationship between abdominal fat deposition and the dysregulation of adiponectin gene expression in adipose tissue.10 It is also interesting that an inverse relationship between adiponectin mRNA expression and tumor necrosis factor-α (TNF-α) has been demonstrated, potentially substantiating the importance of adiponectin as a suppressive mediator of proinflammatory cytokines.28
In short-term aerobic exercise training studies that incorporated a variety of exercise modalities, Bluher et al. demonstrated improvements in plasma adiponectin and Adipo R1/R2 mRNA expression without weight loss in persons with impaired glucose tolerance and T2D.13 In our studies, plasma adiponectin did increase in an absolute sense in MI and HI, and we recognize that the lack of a significant increase in adiponectin might be influenced by the relatively small sample size of our well-controlled, supervised study. However, other studies with either moderate- or high-intensity exercise training also did not find an improvement in plasma adiponectin.16,29 These authors were able to show that changes in visceral adipose tissue and TNF-α were indicative of efficacious changes in the degree of insulin resistance16 and support the contention that changes in the relationship between adiponectin and proinflammatory cytokines such as TNF-α represent their key contribution in the modulation of glucose metabolism.30
In conclusion, the results of studies support the efficacy of short-term, high-intensity aerobic exercise training for the reduction of visceral fat in elderly, overweight adults. The lack of a significant change in abdominal subcutaneous or thigh fat indicate that high-intensity exercise training exerts a preferential influence on the oxidation of visceral fat. Also, the lack of significant changes in plasma adiponectin suggests that moderate-or high-intensity exercise training in the absence of weight loss does not normalize metabolic dysfunction in a short-term intervention. However, the efficacy of long-term, high-intensity exercise training toward the amelioration of insulin resistance has not been well tested, and future studies are needed to identify potential changes in the expression of proinflammatory cytokines in abdominal adipose tissue and their relationship to changes in hepatic and peripheral insulin sensitivity.
This study was supported by National Institutes of Health (NIH) grants KO1 DK 64716-01 (R.H.C.), RO1 AG 19346-01 (W.J.E.), and AHA grant SDA 0335172N (R.H.C.). We also acknowledge support from the University of Arkansas for Medical Sciences General Clinical Research Center funded through grant M01 RR14288. We thank Scott A. Conger and Scott A. Freeling for technical assistance, and Amy D. Sadler for nursing assistance. We also extend our sincere appreciation to our volunteers for their dedication and effort toward the completion of this study.