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The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 7 2275-2277
Copyright © 1997 by The Endocrine Society

Clinical Studies

Leptin Production during Moderate-Intensity Aerobic Exercise1

Susan B. Racette, Simon W. Coppack, Michael Landt and Samuel Klein

Departments of Internal Medicine (S.B.R., S.K.) and Pediatrics (M.L.), Washington University School of Medicine, St. Louis, Missouri 63110; and Department of Medicine (S.W.C.), University College London Medical School, London N19 3UA, United Kingdom

Address correspondence and requests for reprints to: Samuel Klein, M.D., Washington University School of Medicine, 660 South Euclid Avenue, Box 8127, St. Louis, Missouri 63110-1093. E-mail: sklein{at}imgate.wustl.edu


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Leptin, the protein product of the ob gene, may be involved in the regulation of energy balance. Although a clear relationship between energy intake and plasma leptin concentrations has been demonstrated in humans, little is known about the effect of exercise on leptin metabolism. In the present study, we evaluated abdominal adipose tissue leptin production in vivo by arteriovenous balance at rest and during 60 min of moderate-intensity cycle ergometer exercise (50% of maximal heart rate) in five sedentary male subjects (mean age 38.4 ± 1.7 yr, body mass index (28.4 ± 4.2 kg/m2). Blood samples were taken simultaneously from an abdominal vein, draining sc adipose tissue, and a radial artery, at rest and every 10 min during exercise. Adipose tissue blood flow was determined by the xenon washout technique. Plasma leptin concentrations did not change throughout exercise and were the same as the values obtained during resting conditions. Average net adipose tissue leptin production rates during exercise (3.07 ± 0.89 ng/100 g-1· min-1) also were similar to resting values (3.86 ± 0.95 ng/100 g-1·min-1). These results demonstrate that plasma leptin concentrations and leptin production do not change during an acute bout of moderate-intensity aerobic exercise.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
BODY FAT MASS is determined by the cumulative relationship between energy intake and energy expenditure. The characterization of leptin, the protein product of the ob gene, has improved our understanding of the regulation of energy balance. In a seminal study by Pelleymounter et al. (1), exogenous leptin administration decreased body fat by decreasing food intake and increasing physical activity in ob/ob mice. Most studies performed in humans have focused on the interrelationships among body composition, dietary intake, and leptin. These studies have demonstrated that leptin metabolism is regulated by both body fat mass and recent energy intake. Adipose tissue ob messenger RNA (mRNA) expression (2), in vivo adipose tissue leptin production (3), and plasma leptin concentration (4, 5, 6) increase with increasing adiposity. Short-term hypercaloric (7) or hypocaloric (8, 9) feeding acutely increases or decreases plasma leptin concentrations, respectively.

Few studies have evaluated the relationship between physical activity and leptin metabolism. Although long-term exercise training can decrease plasma leptin concentrations by reducing body fat mass (10), Hickey et al. (11) found that an acute bout of exercise did not change plasma leptin concentrations. However, the data reported by Hickey et al. (11) may not be relevant for most of the population, because they studied highly trained athletes undergoing an unusually long and strenuous bout of exercise. Furthermore, measurement of plasma leptin concentrations alone does not provide insight into the dynamic metabolic events that produced the observed values.

Therefore, we performed the present study to evaluate adipose tissue leptin production in vivo during a bout of moderate-intensity exercise in a sedentary population. Leptin production was measured in sc adipose tissue by using standard arteriovenous balance principles. Arterial blood samples, venous blood samples draining sc abdominal fat, and adipose tissue blood flow (ATBF) measurements were obtained during resting conditions and during 1 h of cycle ergometer exercise performed at 50% of estimated maximum heart rate.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subjects

Five male volunteers (mean age 38.4 \ 1.7 yr) participated in this study, which was approved by the Human Studies Committee of Washington University School of Medicine. The subjects included both lean and obese participants (mean height 170.7 \ 4.3 cm, weight 81.3 \ 8.4 kg, and body mass index 28.4 \ 4.2 kg/m2) who had no evidence of medical illness after completing a comprehensive medical evaluation that involved a history and physical examination, blood tests, and an electrocardiogram.

Study protocol

Subjects were instructed to consume their usual weight-maintaining diets, which contained at least 300 g of carbohydrate per day, for 4 days before the study. In the afternoon before each study, subjects were admitted to the General Clinical Research Center, where they consumed a standard meal, providing 100–150 g of carbohydrate, in the evening. The energy content of the meal was adjusted to provide approximately 15 kcal/kg actual BW for the lean subjects and 15 kcal/kg adjusted BW (ideal BW 0.25 x excess BW) in the obese subjects.

The following morning, after the subjects fasted overnight, a 20-gauge catheter was inserted into a radial artery at the wrist to obtain arterial blood samples and a 22-gauge catheter was inserted into an abdominal vein to obtain venous blood draining sc abdominal adipose tissue (12). Approximately 100 µCi of 133Xe dissolved in 0.1 mL of saline was injected slowly into sc abdominal adipose tissue. The subjects rested comfortably in a lying position on a supine cycle ergometer table with their upper body at a 45-degree angle for 120 min after catheter insertion. At 120 min, they began to cycle for 60 min at 50% of their maximal aerobic capacity, as estimated from predicted maximal heart rate based on age. Basal arterial and abdominal venous blood samples were obtained simultaneously at 60, 90, and 120 min to determine basal leptin concentrations, and every 10 min during ergometer cycling to evaluate the response to exercise. Abdominal sc ATBF was measured using the 133Xe washout technique (13). Values were obtained from 60–120 min after injection to determine basal resting ATBF and from 120–180 min after injection to determine ATBF during exercise.

Analyses

Plasma leptin concentrations were determined by RIA using a polyclonal antibody raised in rabbits against highly purified recombinant human leptin (Linco Research Co., St. Louis, MO). In an extensive evaluation, we found this assay was accurate and precise in measuring plasma leptin concentrations ranging from 0.5–100 ng/mL (14).

Calculations

sc ATBF was calculated from 133Xe clearance (13). Adipose tissue plasma flow was calculated as ATBF/(1-hematocrit).

Abdominal adipose tissue net leptin production rates during resting and exercising conditions were calculated by multiplying resting and exercising blood flows by the difference between mean arterial and venous leptin concentrations during rest and exercise, respectively.

Statistical analyses

All values are reported as means \ SE. Differences between exercise-induced changes in plasma leptin concentrations, ATBF, and net leptin production at rest and during exercise were evaluated using a Student’s t test for paired samples. A P-value <= 0.05 was considered to be statistically significant.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Arterial and abdominal venous plasma leptin concentrations during basal conditions and throughout moderate-intensity cycle ergometer exercise for each subject are shown in Fig. 1Go. The average of the three preexercise values for each subject is presented as one basal value. Abdominal vein plasma leptin concentrations were consistently greater than simultaneously collected radial artery plasma leptin concentrations. Basal arterial plasma leptin concentrations ranged from 1.7–13.7 ng/mL and correlated directly with body mass index (data not shown). Mean plasma arterial and venous leptin concentrations during exercise (5.9 \ 2.1 and 7.6 \ 2.6 ng/mL, respectively) were similar to mean values obtained during basal resting conditions (5.8 \ 2.1 and 7.8 \ 2.7 ng/mL, respectively). Furthermore, mean arterial and venous leptin concentrations at the end of the exercise bout (60 min; 6.0 \ 2.2 and 7.3 \ 2.5 ng/mL, respectively) were similar to resting values.



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  		Figure 1. Plasma arterial (upper panel) and abdominal venous (lower panel) leptin concentrations in five male subjects during basal conditions at rest and during moderate-intensity cycle ergometer exercise.

 
Abdominal ATBF increased from 3.0 \ 1.4 mL/100 g-1·min-1 at rest to 4.1 \ 2.5 mL/100 g-1·min-1 during exercise. However, these differences were not statistically significant because of the small number of subjects and the large range of the data.

Mean abdominal adipose tissue net leptin production rates at rest and during exercise are shown in Fig. 2Go. Exercise did not affect the rate of leptin production; the mean abdominal adipose tissue leptin production rate during exercise (3.1 \ 0.9 ng/100 g-1·min-1) was similar to the preexercise value (3.8 \ 1.0 ng/100 g-1·min-1).



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  		Figure 2. sc abdominal adipose tissue leptin production rates (mean + SE) at rest and during moderate-intensity cycle ergometer exercise.

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
The results of the present study demonstrate that a short bout of moderate-intensity exercise does not acutely affect abdominal adipose tissue leptin production or circulating leptin concentrations in humans. Although exogenous leptin administration in ob/ob mice increases physical activity, our data demonstrate that an increase in physical activity does not, in turn, alter leptin metabolism in humans. Our data are consistent with those reported by Hickey et al. (11), who found that plasma leptin concentrations in trained athletes were the same before and after a 20-mile run. Therefore, our findings regarding leptin production during moderate-intensity exercise in sedentary subjects may also apply to other populations performing different exercise activities.

The relationship between exercise and energy balance is complicated and may be influenced by adiposity and gender. Studies performed in carefully controlled metabolic ward conditions have shown that acute bouts of exercise did not affect ad libitum energy consumption in lean women (15). In contrast, the effect of acute exercise on food intake in lean men is not clear, because of conflicting results from different studies (15, 16, 17). A single bout of exercise in male or female obese persons decreases hunger (17) and is not associated with compensatory increases in energy intake (17, 18, 19, 20). Moreover, obese persons who incorporate exercise as part of their weight management program are more likely to comply with their diet and achieve long-term weight management success than those who do not exercise (21, 22, 23, 24, 25, 26, 27). The results from the present study suggest that the effects of exercise on energy intake are unlikely to be mediated by a leptin-related mechanism. However, we cannot exclude the possibility that postexercise alterations in leptin production, related to physical activity itself or negative energy balance, could be involved in regulating food intake after exercise.

Extrapolating our conclusions to whole body leptin production may be problematic, because we measured leptin production in only one adipose tissue site. sc abdominal adipose tissue is the only site suitable for in vivo evaluation by arteriovenous balance methodology. It is possible that leptin production during exercise might have been different at other sites. Masuzaki et al. (28) found that ob gene expression in sc adipose tissue was different than in ip adipose tissue, whereas Hamilton et al. (29) found no difference between sc and ip fat stores. However, it seems unlikely that possible heterogeneity between sc fat and other adipose tissue sites would have had considerable impact on our overall conclusions, because sc fat represents the majority (more than 80%) of total body fat (30).

In summary, sc adipose tissue leptin production and circulating leptin concentrations do not change during a short bout of moderate-intensity aerobic exercise in sedentary human subjects. Further studies are needed to evaluate the effect of long-term exercise training on leptin metabolism.


   Acknowledgments
 
The authors greatly appreciate the nursing staff of the General Clinical Research Center for their help in performing the experimental protocols.


   Footnotes
 
1 This study was supported by NIH Grants DK-49989 and DK-20579, by General Clinical Research Center Grant RR-00036, and by British Heart Foundation Grant PG-95145. Back

Received January 29, 1997.

Revised March 10, 1997.

Accepted March 18, 1997.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

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