Serum Leptin in Children With Obesity: Relationship to Aerobic Exercise, and Percent Body Fat
Introduction
The identification of the adipocyte-specific protein leptin provided the first physiological links to the regulatory system controlling body weight.
In adults, elevations of serum leptin concentrations were closely correlated with the body mass index (BMI). Therefore, in humans, leptin appears to be produced exclusively in adipose tissue (Considine, Sinda, Heiman, Kriauciunas, 1996; Maffei, Halaas, Ravussin, Pratey, 1995) and is secretes into the blood (Chomczynski & Sacchi, 1987).
Hassink, Sheslow and Lancey(1996) indicated that the mean serum concentration of leptin in the obese group was 38.6(±21)ng/ml conpared with 7.8(±6.5) ng/ml in the control group. They further reported that serum leptin concentrations were hightly correlated with BMI (r= .88). They concluded that obese children have high concentrations of serum leptin, which were highly correlated with arm fat and BMI.
Recently, Dagogo-Jack, Tanellis, Paramore, Brother, and Land (1996) reported that the mean plasma leptin concentration in the obese subjects was 37.2 ±3.6ng/ml, as compared with 14.2±2.2ng/ml in 9 men (BMI = 26±0.7) was 9.5±1.1ng/ml, as compared with 19.8±2.5ng/ml in 14 aged-matched women (BMI = 25.2±0.8), all of whom were not obese. Furthermore, the correlation between BMI and leptin was not significant in the non-obese group (r= 0.02), but that in obese group their was a strong significance (r= 0.84, p= 0.0005).
It is thought that there is integral in the feedback loop from adipose stores to the satiety centers in the hypothalamus (Considine et al., 1996). The main function of leptin is causing a decrease in appetite and an increase in energy expenditure.
In normal and obese adults, the amount of ob messenger RNA in adipocytes correlated with body weight (Lonnquist, Arner, Nordfors, Schalling, 1995).
Considine et al. (1996) reported that leptin was detected in the serum of obese and normal-weight adults, with obese adults having significantly higher serum leptin concentrations than did normal-weight adults. They concluded that the elevations of serum leptin concentrations were highly correlated with the percentage of body fat.
Recent reports indicate that circulating leptin is positively correlated with body fat in humans and, furthermore, that leptin concentration is approximately four times higher in obese than in normal weight humans (Considine, Sinha, Heiman, Kriand, 1996). Although the physiological mechanisms that contribute to leptin production and metabolism are not quite clear, diet-induced weight loss lowers both serum leptin and adipose tissue ob mRNA (Considine et al., 1996). But it is unknown whether there is a relationship between acute or chronic exercise and leptin concentration.
Pelleymounter, Cullen, and Baker (1995) reported that administration of recombinant leptin in rodent models of obesity leads to increased thermogenesis and reduced food intake. They explicitly suggested that leptin has biological effects that can be contributed to appetite regulation.
The most important point of leptin regulation in children may not be the same as adults, because there is a dynamic relationship between energy needs and expenditure for their growth and development. It is possible that leptin may function differently in developing children than in adults.
The purpose of the present study was to investigate whether leptin can be detected in the serum of obese children and whether serum leptin levels were directly affected by chronic endurance exercise training.
Research Design and Methods
Subjects
Table 1 displays demographic and anthropometric data for obese children. The group was composed of 25 children (7 girls and 18 boys) with a mean age of 11.75±0.74 years. The mean BMI for the obese children were 27.51±2.00, 26.39±2.38 and 26.16±2.38 (weight/height2). These child subjects along with their parents gave informed consent. The study was approved by the Graduated School at National Pingtung Teachers College and National Zong-Ming Hospital in Taipei, Taiwan.
Table 1: Demographic and Anthropometric Variables of Subjects
| Variables | Height (cm) | Weight (kgw) | Body Fat (%) | W/H ratio (weight/height2) | BMI | |
|---|---|---|---|---|---|---|
| Pre-Test | M | 151.41 | 63.07 | 35.42 | 0.96 | 27.51 |
| SD | ±6.81 | ±8.77 | ±1.26 | ±0.04 | ±2.00 | |
| Mid-test | M | 153.50 | 62.68 | 32.59 | 0.88 | 26.39 |
| SD | ±7.41 | ±10.31 | ±1.68 | ±0.03 | ±2.38 | |
| Post-test | M | 154.71 | 63.00 | 31.99 | 0.89 | 26.16 |
| SD | ±7.69 | ±10.42 | ±2.80 | ±0.04 | ±2.38 |
Blood Sample
All blood samples were collected from each child after an over-night (at least 12 hrs) fast. The serum was frozen at -80? until analysis. Radioimmunoassay (RIA) for serum leptin and insulin was performed as previously indicated on Considine et al. (1996). Weight was measured to the nearest 0.1 kg on a balance beam scale, and height was measured by stadiometer to the nearest centimeter, then BMI was calculated by body height and weight (weight/height2) (Najjar & Rowland, 1989).
Body Composition Measures
Measurement of triceps, subscapular, abdomen, and thigh skin folds were measured and triceps and subscapular calculated for percentage of body fat. The procedure are based upon the formulas provided by Lohman (1989).
- The equation is as follows,
%Fat = 1.35X - 0.012(X)2 - Intercept.
Aerobic Exercise Training Program
All obese children completed an aerobic exercise training program for five days a week, twelve weeks in total. The program included a 30-minute walk and run, and 40-minute areobic dancing class. Mean heart rate was 136±11 beats/min after activity.
Subjects were instructed not to change their life style during the 12-week experiemental period, especially during the pre-, mid-and post-tests.
Statistical Analysis
Descriptive statistics (mean ±SD) were computed for all continuous mediating variables (eg. anthropometric variables, percent body fat, heart rates, and leptin, high lipoprotein cholesterol, TG, total cholesterol). Simple correlations among outcome variables were also calculated ANOVA analysis was performed to compare of pr-, mid and post-test data in serum factors and the percentage of body fat. Owing to the scatter in serum leptin, insulin, and percent body fat values, the relationship among those continuous variables under basal conditions was analyzed using Pearson correlations.
Results
Table 2 presents laboratory findings for the obese children. The mean serum leptin concentrations in the obese children were 15.89 ±6.65, 14.67 ±5.27 and 11.70 ±4.99 ng/ml for pre-, mid-, and post-tests. Circulating leptin concentration is decreased with a similar degree of increase in plasma insulin concentrations for the group.
Table 2: Laboratory Variables of Subjects
| Variables | Leptin (ng/ml) | Insulin (uU/ml) | Calcium (mg/dl) | Glucose (mg/dl) | HDL-c (mg/dl) | TC/HDL-c | |
|---|---|---|---|---|---|---|---|
| Pre-Test | M | 15.89 | 24.06 | 8.5 | 73.94 | 34.94 | 6.79 |
| SD | ±6.65 | ±11.64 | ±0.81 | ±16.89 | ±24.11 | ±0.45 | |
| Mid-test | M | 14.67 | 23.47 | 9.93 | 96.4 | 76.60 | 2.40 |
| SD | ±5.27 | ±13.18 | ±0.43 | ±5.32 | ±20.75 | ±0.39 | |
| Post-test | M | 11.70 | 36.91 | 10.20 | 98.46 | 69.69 | 3.65 |
| SD | ±4.99 | ±13.00 | ±0.41 | ±6.39 | ±21.32 | ±1.74 |
For the obese children, serum leptin concentrations were highly correlated with fasting insulin levels (r= -0.88, -0.68, and - 0.72 for pre-, mid-, and post-tests) and percent body fat (r= 0.46, 0.82, and 0.74 for pre-, mid-, and post-tests). Detailed information on the relationship among variables is summarized in
Table 3: The relations among serum leptin, insulin percent body fat, hip/waist ratio, and body mass index (N=25)
| Pre-Test | ||||
|---|---|---|---|---|
| Leptin | 1.00 - 0.88** | 0.46* | 0.68* | 0.47* |
| Insulin | 1.00 | 0.44* | 0.64* | 0.69* |
| %Fat | 1.00 | 0.60* | 0.41* | |
| W/H ratio | 1.00 | 0.56* | ||
| BMI | 1.00 |
| Mid-Test | ||||
|---|---|---|---|---|
| Leptin | 1.00 - 0.68* | 0.82** | 0.61* | 0.42* |
| Insulin | 1.00 | 0.65* | 0.78** | 0.63* |
| %Fat | 1.00 | 0.48* | 0.89** | |
| W/H ratio | 1.00 | 0.69* | ||
| BMI | 1.00 |
| Post-Test | ||||
|---|---|---|---|---|
| Leptin | 1.00 - 0. 72** | 0.74** | 0.46* | 0.39* |
| Insulin | 1.00 | 0.12 | 0.24 | 0.14 |
| %Fat | 1.00 | 0.07 | 0.35* | |
| W/H ratio | 1.00 | 0.78* | ||
| BMI | 1.00 |
Table 4 presents the reslationship between serum leptin concentration and skinfold thicknesses. For all obese children, serum leptin concentrations demonstrated a higher correlation with triceps (r= 0.66, 0.88, and 0.90: pre-, mid-, and post-tests).
Table 4: The relations between serum leptin and skinfold thicknesses (N=25)
| Variables | Triceps | Abdomen | Subscapular | Thigh |
|---|---|---|---|---|
| Pre-Test | 0.66 | 0.75 | 0.74 | 0.66 |
| Mid-Test | 0.88 | 0.69 | 0.75 | 0.73 |
| Post-Test | 0.90 | 0.59 | 0.76 | 0.69 |
Discussion and Conclusion
In this study serum leptin level was found in high concentrations in obese children, which is highly correlated with percentage of body fat, the indirect measures of adiposity used in this study. The present study provides the first evidence for an independent relationship between serum leptin and percent body fat. As body fat increases, so does the range of reported plasma leptin concentrations at any given level of body fat (Segal, Landt and Klein, 1996). In addition, Dagogo-Jack et al. (1996) found a strong correlation between serum leptin and BMI (r= 0.95, p<0.05). Furthermore, Plasma leptin concentrations were also correlated with fasting serum insulin concentrations. It is further document on the plasma leptin and insulin mechanism (Kolaczynski, Nyce, Considine, Boden, 1996).
Finally, the results of the present study indicate differences in the degree of serum insulin concentration and percent body fat that may explain the interaction with serum leptin during exercise training. In conclusion, the present study provides direct evidence that leptin is produced by adipose tissue in obese children and the rate of production is directly related to adiposity.
References
Campfield, L. A., Smith, F. J., Guisez, Y., Devos, R., & Burn, P. (1995). Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neuronal networks. Science, 269, 546-549.
Considine, R. V., Sinha, M. K., Heiman , M. L., Kriauciunas, A, Stephens, T. W., Nyce, M. R. Ohannesian, J. P., Marco, C. C., Mckee, L. J., Bauer, T. C., & Caro, J. F. (1996). Serum immunoreactive-leptin concentrations in normal-weight and obese humans, New England Journal Medicine, 334, 292-295.
Dagogo-Jack, S., Tanellis, C., Paramore, D., Brother, S. J., & Land, T. M. (1996).
Plasma Leptin and Insulin Relationships in Obese and Nonobese Human, Diabetes, 45, 695-698.
Frederick, R., Lowel, B., Kahn, O. B., Haman, A., & Flier, J. (1995). Nutritional regulation of ob gene mRNA in White adipose tissue, 77th Annual Meeting of The Endocrine Socitey Proceedings. OR 25-3a (Abstration).
Halaas, J. L., Gajiwala, K. S., Maffei, M., Cohen, S. L., Chait, B. T., Rabinowitz, D., Lallone, R. L., Burley, S. K., Friedman, J. M. (1995). Weight-reducing effects of the plasma protein encoded by the obese gene. Science, 269, 543-546.
Hamilton, B. S., Paglia, D., Kwan, A. Y. M., & Deitel, M. (1995). Increased obese MRNA expression in omental fat cells from masssively obese humans. Nature Medicine, 1, 953-956.
Kolaczynski, J.W.; Nyce, M.R.; Considine, R.V.; Boden, G.; Nolan, J.J.; Henry, R.; Mudaliar, S.R.; Olfasky, J., & Caro, J.F. (1996). Acute and Chronic Effect of Insulin on Leptin Production in Humans. Diabetes, 45, 699-701.
Klein, S., Coppack, S. W., Mohamed-Al:, V., & Landt, M. (1996). Adipose tissue leptin production and plasma leptin kinetics in humans. Diabetes, 45, 984-987.
Lonngvist, F., Arner, P., Nordfors, L., & Schalling, M. (1995). Overexpression of the obese (ob) gene in adipose tissue of human obese subjects. Nature Medicine, 1, 950-953.
MacDougald, O. A., Hwang, C. S., Fan, H., & Lane, M. D. (1995). Regulated expression of adipocytes. Processings National Academy Sciences of U. S. A. 92, 9034-9037.
Maffei, M., Halaas, J., Ravussin, E., Pratley, R. E., Lee, G. H., Zhang, Y., Fei, H., Kim, S., Lallone, R., Ranganathan, S., Kern, P. A., & Friedman, J. M. (1995). Leptin levels in human and rodent: measurement of plasma leptin and ob NAN in obese and weight-reduced subjects. Nature Medicine, 1, 1155-1161.
Murakami, T., & Shima, K. (1995). Colonning of rat obese cDNA and its expression in obese rats. Biochemistry Biophysiology Research Communication, 209, 944-952.
Pelleymounter, M. A., Cullen, M. J., Baker, M. B., Hecht, R., Winters, D., Boone, T.,
Collins, F. (1995). Effects of the obese gene product on body weight regulation in ob/ob
mice. Science, 269, 540-543.
Rohner-Jeanrenaud, F. & Jeanrenaud, B. (1996). Obesity, leptin, and the Brain,
New England Journal Medicine, 334, 324-325.
Sandra, G., Hassink, M. D., Sheslow, D. V., Lancey, E., Opentanova, I., Considine,
R. V., & Caro, J. F. (1996). Serum leptin in children with obesity. Relationship to gender and development, 98, 201-203.
Sinha, M. K., Ohannesian, J. P., Heiman, M. L., Kriauciunas, A., Stephens, T. W., Magosin, S., Marco, C., & Caro, J. F. (1996). Journal of Clinical Investigation, 97, 1344-1347.
Segal,K.R.; Landt, M., & Klein, S. (1996). Relationship Between Insulin Sensitivity and Plasma Leptin Concentration in Lean and Obese Men. Diabetes, 45, 988-991.
Trans, L. D., Elston, R. C., Keats, B. J. B. & Wilson, A. F. (1994). Sib-pair linkage program (SIBPAL). In S. A. G. E.: Statistical Analysis for Genetic Epidemiology, Release 2.2. New Orleans, LA, Louisiana State University.
In most cases, the genes involved in gaining weight do not directly “cause” obesity. Although there have been landmark discoveries recently to the gene contributions to the development of obesity, such as congenital leptin deficiency, it appears that the gain in fat is more related to living in an environment characterized by an abundance of food. The good news is that in people who have a genetic tendency, it can be avoided with the development of healthy eating and exercise behaviors. (LaFontain and Roitman. “Lifestyle Management of Obesity.” Etiology of Obesity, 2003, pp. 1-3.)