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Original Studies |
Department of Exercise Science, Syracuse University (J.A.K., M.M.W.D., E.B.J.), Syracuse, New York 13244; and the Department of Medicine, University of Virginia Health Sciences Center (M.L.H.), Charlottesville, Virginia 22908
Address all correspondence and requests for reprints to: Jill Kanaley, Ph.D., Syracuse University, 820 Comstock Avenue, Room 201, Syracuse, New York 13244. E-mail: jakanale{at}sued.syr.edu
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Acute aerobic exercise is also a provocative stimulus of GH release in
NonOb individuals. The magnitude of response is influenced by the mode
of exercise, intensity, duration, aerobic vs. anaerobic
exercise, and intense chronic training (10, 11, 12, 13, 14). In nonobese
individuals, an exercise bout of moderate intensity [
65% oxygen
consumption (VO2) peak] and a minimum of 20 min in
duration will elicit a GH response (15, 16), which appears to override
endogenous signals for almost a 3-h period (17). One year of chronic
aerobic training has been found to increase spontaneous 24-h GH release
in women (13), whereas short term training (6 weeks) decreased the GH
response to acute constant load exercise (18). In morbidly obese
patients, the GH response to exercise was increased with weight
reduction (19).
In addition, GH secretion may be impacted by body fat distribution. Abdominal obesity and increased visceral fat have been associated with lower serum IGF-I concentrations (20, 21), decreased spontaneous 24-h GH release (22, 23), and diminished responses to pharmacological stimuli (24). Therefore, differences in body fat distribution may alter the GH response to exercise. Although it has been demonstrated that exercise of adequate stimulus will elicit a GH response in NonOb individuals, the impact of acute or chronic exercise training has not been well studied in obese subjects. The purpose of this study was to determine whether exercise stimulates a GH response in obese women compared to NonOb women, and if regional body fat distribution influences the GH response to acute exercise. Further, we examined the effect of a 16-week aerobic exercise training program on the GH response to acute exercise. We hypothesized that obese women would have a decreased GH response to exercise and that this would be more pronounced in women with upper body obesity (UBO) than in women with lower body obesity (LBO). We also postulated that exercise training would increase both resting and exercise GH concentrations in obese women.
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Subjects and Methods |
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Eight NonOb, 11 LBO, and 12 UBO women were recruited for this study. All subjects provided voluntary, written informed consent, as approved by the institutional review board. The LBO women had a waist/hip ratio less than 0.76 (waist, <95 cm), and the UBO women had a waist/hip ratio greater than 0.85 (waist, >95 cm). The NonOb women recruited had a body mass index (BMI) less than 24 kg/m2, whereas the obese women had a BMI in the range of 29–35 kg/m2. No subjects had a history of pituitary, renal, hepatic or metabolic diseases. No subjects were smokers, nightshift workers, or taking any medications known to affect GH secretion. None of the women were taking oral contraceptives, and the women were studied between days 5–10 of their menstrual cycles. The subjects had not undergone transmeridian travel in the past 2 months and were not allowed to exercise for 24 h before each evaluation.
Experimental design
Both the obese and NonOb women underwent the initial testing, which involved measurement of aerobic capacity and body composition. Upon completion of the initial testing, all subjects returned on another day for 7 h of testing. On this visit, each subject completed a resting metabolic rate study (SensorMedics 2900, Yorba Linda, CA) to estimate 24-h energy expenditure, followed by blood sampling at 5-min intervals for 6 h. After 1 h of baseline measures, all subjects exercised at an intensity that corresponded to 70% of VO2 peak for 30 min, followed by recovery for 4.5 h. The obese women then initiated a 16-week aerobic training program. The obese subjects were retested at the completion of the training for all of the above tests.
Body composition
Percent body fat was assessed by both skinfold thickness (25) and bioelectrical impedance (26). The equations of Lemieux et al. (27) were used to estimate visceral fat area based on waist circumference measurements.
VO2 peak
Maximal oxygen consumption was determined using a continuous treadmill protocol. Subjects started walking at 3.0 mph for 2 min, which increased to 3.5 mph for 2 min, and then every 2 min thereafter treadmill grade was increased by 2.5% until volitional fatigue. VO2 peak was chosen as the highest VO2 attained. Heart rate was determined by electrocardiogram. Maximal exercise was believed to be achieved if the respiratory exchange ratio value was greater than 1.1, ratings of perceived exertion (RPE) were greater than 16 (very hard; (28))and each subject approached their age predicted maximal heart rate. If this criteria was not met then we repeated the max test.
Study day
After a 12-h overnight fast, at 0600 h an iv cannula was placed in a forearm vein. The resting metabolic rate was measured by indirect calorimetry for 30 min after 30 min of quiet resting in a thermoneutral environment. To determine the 6-h profile of endogenous GH secretion, blood was sampled at 5-min intervals from 0700–1300 h. At 0800 h subjects walked on the treadmill for 30 min at 70% VO2 peak. Throughout the blood-sampling period, subjects remained awake and fasted to avoid the confounding effects of these variables on GH secretion. All subjects were asked to keep a 3-day dietary record before each study day.
Exercise training
Only the obese subjects participated in the exercise training portion of the study. Training consisted of supervised training 3 days/week for 4 months. Workouts included 5 min of stretching, 20–40 min of aerobic exercise (primarily on the treadmill but included other equipment as training time increased), followed by 5 min of cool down. Exercise prescription was individually based with a target heart rate of 65–80% of maximum heart rate. Subjects were also encouraged to keep the RPE value greater than 13 (somewhat hard) (28) during the workouts. The aerobic duration of exercise was gradually increased from 20 to 40 min/session as tolerated. Training logs were kept to record the exercise performed, and the subjects who underwent the posttesting completed at least 85% of the training sessions.
GH assays
All samples for an individual subject were run in the same assay, and samples were measured in duplicate by a modified GH chemiluminescence assay (Nichols Institute Diagnostics, San Juan Capistrano, CA; enhanced sensitivity to 0.002 µg/L) (29). The mean intra- and interassay coefficients of variation were 4.5% and 5.1%, respectively. The GH concentrations were determined from standard curves and response functions to optimized variably weighted response data (30). Briefly, standard curves were evaluated by weighted nonlinear least squares analysis using three response functions. Uncertainties (SD) associated with each GH concentration were estimated empirically, considering variances associated with both assay response and standard curve evaluations. The standard curve parameters and response function to the variably weighted response data were optimized. Confidence limits for the standard curve parameters were then calculated (30). The function yielding the lowest absolute sum of squared residuals was chosen for analyzing the samples.
Data analysis
Integrated GH concentrations (area under the curve) were calculated using Cluster analysis (31). In addition, multiple parameter deconvolution analysis was employed to derive estimates of the attributes of GH secretory events. Each pulse was approximated by a Gaussian distribution of secretory rates. GH pulses were considered significant if the amplitude could be distinguished from zero (P < 0.05). A monoexponential GH half-life was estimated and held constant throughout this analysis, as was the GH secretory pulse half-duration and GH distribution volume (32). The pulsatile GH production rate was estimated as the product of the number of secretory pulses and the mean GH mass secreted per pulse.
ANOVA (SAS Institute, Inc., Cary, NC) was employed to
determine mean differences between groups (LBO, UBO, vs.
NonOb), and paired t tests were used to determine pre- and
posttraining differences. Preplanned mean comparisons were conducted
using the Tukey test when mean differences were observed. Pearson
product-moment correlation and a partial correlation (adjusted for
total body fat and percent body fat) were employed to test for
relationships among 6-h integrated GH concentrations and measures of
body fat. All values are expressed as the mean ±
SE. An 
level of 0.05 was chosen a
priori.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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. The NonOb women had significantly
lower weight, BMI, and percent fat and a smaller waist measurement than
either of the obese groups. In addition, the NonOb women had a greater
aerobic fitness level than both obese groups, but this was only
significant compared to the UBO women. Visceral fat area was estimated
using the waist measurement (27), and this revealed significant group
differences (P < 0.05), such that NonOb women had
49.6 ± 4.2 cm2, LBO women had 100 ± 4.5
cm2, and UBO women had 141.2 ± 3.7 cm2 of
visceral fat.
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illustrates the GH response over
the 6 h of testing. In each group an increase in mean serum GH
concentrations was seen in response to the exercise stimulus. The mean
baseline GH concentration (0700–0800 h) for the NonOb women was 1.82
µg/L compared to 0.60 and 0.41 µg/L for the LBO and UBO women,
respectively. In response to exercise, the peak GH concentration for
each group was 13.7, 6.78, and 3.49 µg/L, respectively. The mean
integrated serum GH concentrations during 6 h of blood sampling in
all groups are shown in Fig. 2a. During
this period, the subjects exercised for 30 min, and the GH response was
greater (P < 0.05) in the NonOb women than in the LBO
and UBO women. No statistically significant differences were found
between the obese women when separated by body fat distribution.
Six-hour GH concentrations were significantly correlated with visceral
fat (r = -0.65; P < 0.01), but there was no
significant correlation when visceral fat was adjusted for total body
fat (r = -0.13; P = 0.50). Using deconvolution
analysis (Table 2), the greater GH
response in the NonOb women could be accounted for by a greater 6-h GH
production rate in these women (NonOb, 45.6 ± 12.3; LBO,
17.0 ± 5.8; UBO, 8.1 ± 1.3 µg/LV;
P < 0.05). This was due to a significantly increased
mass of GH secreted per pulse in the NonOb women compared to the obese
women. The number of GH secretory pulses, the GH secretory pulse
half-duration, and the GH half-life did not differ significantly
between groups (Table 2).
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. Only 10 obese women, 5
LBO and 5 UBO, completed the 16 weeks of training and posttesting. Only
those women completing both study days were included in this part of
the analysis. The women who dropped out of the study did so for a
variety of reasons, ranging from not enough time to not losing weight
fast enough. No one dropped out due to injuries. The women who
completed the training are representative of the entire group of obese
women, as their descriptive characteristics did not vary from those of
the original group. The women who completed the 16 weeks of training
were representative of the women who were originally studied. We
collapsed across the UBO and LBO groups, because no significant group
difference was found in the GH response before training. No significant
change in weight, fat-free mass (FFM), or fat mass was observed with
the exercise training. In response to training, the aerobic capacity
increased from 44.7 ± 2.2 to 48.5 ± 1.9 mL/kg
FFM·min-1; P < 0.05). No changes were
observed in the 6-h integrated GH concentrations as a result of the
aerobic training (pre, 379 ± 144; post, 350 ± 55
min/µg·L-1, respectively). |
Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The few studies that have investigated the GH response to exercise in
obese subjects have reported variable results (34, 35, 36). These earlier
studies employed a variety of different exercise protocols and usually
observed no GH response. The studies used relatively low exercise
intensities [225 kg/m2 for 60 min (36)] or short
durations of exercise [15 min at 70% of the predicted maximum heart
rate (35); 10 min at 70% VO2 max (34)]. In normal weight
individuals, it has been shown that aerobic exercise with a duration of
at least 20 min at an intensity of 60–70% VO2 max is
needed to elicit a GH response (16). The present study used an
intensity of 70% VO2 max and a duration of exercise of 30
min. In addition, frequent blood sampling (5-min intervals), a highly
sensitive GH chemiluminescence assay (sensitivity, 0.002 µg/L) and
deconvolution analysis were employed so that low levels of GH secretion
could be accurately characterized in these obese subjects (3, 4).
Unlike these earlier reports, we found that each obese subject did
display a GH response to exercise, although the magnitude of the
response was attenuated compared to that in the age-matched nonobese
subjects. The lower GH concentrations observed in the obese subjects
were due to lower GH production rates compared to those in the nonobese
women. A reduction in the mass of GH secreted per pulse in the obese
compared to the nonobese women accounted for the reduced rates of GH
secretion. There was no difference in the number of GH secretory pulses
observed or in the half-life of GH clearance between the obese and
nonobese subjects. Previous studies of GH secretion and clearance in
obese subjects at rest revealed a similar reduction in GH production
rates and the mass of GH secreted per pulse (3, 4). However, these
researchers also reported a decreased GH half-life in resting subjects
with a higher percentage of body fat (3, 4). In the present study, the
mean GH half-lives in the obese women (13–16 min) are somewhat
shorter than previously reported in resting normal nonobese young men
(17–20 min) (37, 38, 39). The half-life values were not as short as
those previously observed in resting obese men (11 min) (3), yet the
values overlap with those reported in exercising nonobese men (11–17
min) (33, 40). Thus, it is possible that both obesity and exercise are
associated with an increased rate of GH elimination, and this might
explain why no difference was observed in GH half-lives between the
obese and nonobese subjects in this study.
Body fat distribution and aerobic fitness have also been suggested as important regulators of GH secretion. Relative adiposity and VO2 peak have been shown to have significant inverse relationships with 24-h integrated GH concentrations in men (4, 14), although these relationships appear to be weaker in women (14). In the present study, aerobic fitness, defined as VO2 peak (milliliters per kg FFM/min), was slightly higher in the NonOb women, but a significant correlation between fitness or percent fat and the 6-h GH response was not observed. Abdominal obesity, specifically increased amounts of abdominal visceral fat, is associated with lower serum IGF-I concentrations (20, 21) and 24-h GH release (22, 23). However, the impact of body fat distribution on the acute GH response to exercise has not been carefully studied. In the present study, the GH response to exercise did not differ significantly between LBO and UBO women. The amount of abdominal visceral fat, estimated from waist circumference, was significantly higher in the UBO women than in the LBO and NonOb women. There was no relationship between the estimated visceral fat adjusted for total body fat and the exercise-induced GH response. These data suggest that in women, the percent body fat may be a more important determinant of the GH response to exercise than is the regional distribution of body fat. As visceral fat was not measured directly in this study, this conclusion should be regarded as tentative. A previous study has reported that the GH response to pharmacological stimuli is inversely related to the amount of visceral fat measured by computed tomography (24).
The attenuation of the GH response to exercise in obese subjects is similar to that observed in response to pharmacological stimuli of GH secretion, including insulin-induced hypoglycemia, GHRH, arginine, L-DOPA, clonidine, pyridostigmine, GH-releasing peptide, and various combinations of these pharmacological agents (5, 6, 41, 42, 43, 44). Comparison of the present results with these previous studies suggests that in obese subjects the magnitude of the GH response to exercise is greater than that to L-DOPA and clonidine (41, 44), similar to that observed with GHRH, pyridostigmine, and arginine (5, 6, 41, 42, 43, 44), and lesser than the response to GH-releasing peptide and tests employing combinations of agents (42, 43, 44). However, this reduction in GH secretion in obesity is not an absolute or permanent defect. Prolonged fasting or significant weight loss (5, 6) will restore GH to levels observed in fed normal subjects. GH responses to other provocative stimuli are also increased by weight loss (6, 19, 45). In addition, 24-h GH release in obese subjects is significantly increased by 5 days of fasting (7), although not to the same absolute levels as those observed in nonobese young men (39). Although 24-h GH release is not increased by maintaining a very low calorie diet for 4 days (8), massive weight loss will restore 24-h GH release to normal levels (9). These observations suggest that the metabolic milieu associated with obesity results in negative feedback on the neuroendocrine mechanisms controlling GH secretion. The present data suggest that in obese individuals, exercise of sufficient intensity and duration can stimulate GH release despite these metabolic negative feedback signals, although the response is diminished, as with other known stimuli for GH secretion.
The precise mechanisms that account for reduced GH secretion in obesity
and an increase in GH secretion with exercise have not been determined
in man. In obesity, GH secretion may be inhibited by increased
hypothalamic somatostatin secretion and/or increased action. This
hypothesis is supported by the observations that administration of
cholinergic agonists and arginine, which are thought to inhibit
somatostatin release, will enhance the GH response to GHRH (41, 43).
Metabolic factors such as increased serum concentrations of insulin,
free IGF-I, and free fatty acids may influence GH secretion at the
level of both the pituitary and the hypothalamus (46, 47). Exercise is
thought to stimulate GH secretion via effects on the hypothalamus; both
stimulation of GHRH secretion and inhibition of somatostatin release
have been postulated. It has been suggested that sympathetic activity
is an important mediator of the GH response to acute exercise, possibly
via activation of central 2-adrenergic neurons (2, 18).
It is likely that the same metabolic factors that result in attenuation
of the GH response to pharmacological stimuli also inhibit the GH
response to exercise in obese subjects.
The integrated GH concentration observed in response to acute exercise at the same relative intensity (70% VO2 peak) was not changed by 16 weeks of aerobic exercise training. The obese subjects who completed the training did experience a training effect, as the VO2 peak was increased by 8.5%. It was important to conduct the exercise tests pre- and posttraining at the same relative intensity rather than with a constant work load, because a previous study demonstrated that training decreases the GH response to acute, constant load exercise (18). We had hypothesized that training would increase the GH response to acute exercise of the same relative intensity based on previous observations that aerobic training of young NonOb women for 1 yr resulted in increased 24-h integrated GH concentrations (13). Although we noticed no change in the 6-h GH response to exercise pre- and posttraining, this does not necessarily indicate that the amount of GH secreted over a 24-h period was not changed by the training. Furthermore, it is also possible that a training period longer than 16 weeks is required to increase the GH response to exercise. Although the obese subjects in the present study did improve their aerobic exercise capacity after 16 weeks of training, they did not experience any change in weight, fat mass, or FFM. These findings suggest that the GH response to exercise in obese subjects will only be increased when significant loss of body fat accompanies improvements in aerobic exercise capacity induced by training. Most likely, this would require a longer duration or greater intensity of exercise training. An alternative hypothesis might be that the reduced GH response to exercise might have limited the efficacy of exercise training to alter the body composition of these subjects.
In summary, serum GH concentrations in obese women are increased by exercise of sufficient intensity and duration, although this GH response is suppressed compared to that in NonOb women. A reduction in the mass of GH secreted per pulse is the primary mechanism responsible for the lower serum GH concentrations after exercise in obese vs. NonOb women. Although UBO women tend to have a lesser GH response to exercise than LBO women, the impact of body fat distribution on the GH response to exercise appears to be weaker than that of obesity per se. Sixteen weeks of aerobic training did not alter the GH response to exercise despite the fact that the aerobic exercise capacity improved. This does not preclude the possibility that a longer training period that induces decreases in body fat mass might increase the GH response to exercise.
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Acknowledgments |
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Footnotes |
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2 Current address: Eli Lilly & Co., Lilly Corporate
Center, Drop Code 4126, Indianapolis, Indiana 46285.
Received February 12, 1999.
Revised April 26, 1999.
Accepted June 18, 1999.
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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