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The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 10 3574-3577
Copyright © 1998 by The Endocrine Society

Original Studies

Serum Leptin Concentrations in Caucasian and African-American Girls1

William W. Wong, Margery Nicolson, Janice E. Stuff, Nancy F. Butte, Kenneth J. Ellis, Albert C. Hergenroeder, Rebecca B. Hill and Elliot O. Smith

United States Department of Agriculture/Agricultural Research Service Children’s Nutrition Research Center (W.W.W., J.E.S., N.F.B., K.J.E., E.O.S.) and Texas Children’s Hospital (A.C.H., R.B.H.), Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030; and Amgen, Inc. (M.N.), Thousand Oaks, California 91320

Address all correspondence and requests for reprints to: William W. Wong, Ph.D., United States Department of Agriculture/Agricultural Research Service Children’s Nutrition Research Center, 1100 Bates Street, Houston, Texas 77030. E-mail: wwong{at}bcm.tmc.edu


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Because African-American girls are heavier, taller, and mature earlier than Caucasian girls, we hypothesized that the serum leptin concentration differs between the two groups. Serum leptin concentrations were measured by immunoassay in 12-h fasted blood samples collected from 79 Caucasian and 57 African-American girls between 8 and 17 yr of age. Body composition was measured by dual-energy x-ray absorptiometry, sexual maturity by physical examination, and physical fitness by treadmill testing. Serum leptin concentrations were positively correlated (P < 0.01) with maturation, body fatness, and insulin and were higher (6.6 ng/mL, P < 0.01) in the African-American girls after adjusting for age. The difference remained significant (P < 0.01) but was reduced to 3.2 ng/mL after controlling for differences in maturation, fat mass, and physical fitness. The higher serum leptin levels might play an important role in the accelerated growth and sexual maturation of African-American girls.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
LEPTIN is synthesized and secreted exclusively in adipose tissue (1, 2). Injection of recombinant leptin in ob/ob mice reduced food intake and body weight, with concomitant increases in the metabolic rate and activity levels (3). Radioiodinated leptin crossed the blood-brain barrier intact and was found at the choroid plexus and arcuate nuclei of the hypothalamus (4). The involvement of the central nervous system in the action of leptin is supported by the reduction in food intake and body weight, in a dose-dependent manner, in ob/ob mice (5) and lean Long-Evans rats (6) after intracerebroventricular injection of recombinant leptin.

Serum leptin concentrations were lower in lean, adult rhesus monkeys than in obese monkeys and were significantly related to body weight and body fat (7). Similar findings were reported in humans, including children (8, 9, 10, 11). Serum leptin concentrations were also higher in females than in males at any given adiposity (9, 12).

Earlier studies demonstrated that African-American children were taller, heavier, and more mature sexually than Caucasian children of similar age (13, 14, 15, 16, 17). Because serum leptin concentrations are strongly correlated with body fat (1, 7, 8, 9, 10, 12, 18, 19, 20), fat mass (FM) (and hence, leptin) might be related to the onset of puberty and menstruation (2). The hypothesis is supported by a recent study showing that a rise in the serum leptin concentration preceded a rise in sex hormones (21). Because sexual development and menses also begin 1–2 yr earlier in African-American girls than in Caucasian girls (17), we hypothesized that the serum leptin concentration might differ between the two groups.


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

A group of healthy, nondiabetic Caucasian and African-American girls (Table 1Go) from the greater Houston metropolitan area was studied. The protocol conformed with the Occupational Safety and Health Administration/Health and Human Services guidelines for human immunodeficiency virus/hepatitus B virus occupational safety and was approved by the Human Research Committee at Baylor College of Medicine. All subjects and their parents gave written informed consent. Body weight and height of each subject were measured by one investigator. Sexual maturity, according to the Tanner stages of classification (22), was determined by physical examination.


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  		Table 1. Age, sexual maturity stage, physical characteristics, body composition, O2max, and serum insulin concentrations of Caucasian and African-American subjects

 
Serum leptin procedures

Leptin concentrations in serum samples obtained in the morning, after a 12-h fast, were measured in a solid-phase sandwich enzyme immunoassay. Leptin concentrations were calculated from standard curves generated for each assay using recombinant human leptin. The minimal detection limit of the assay was 70 pg/mL. The intra- and interassay coefficients of variation were 3% and 8%, respectively.

Physical fitness evaluation

The physical fitness of each girl (O2max) was measured on a motorized treadmill, using the modified Bruce protocol, until volitional exhaustion (23). Oxygen consumption rate (O2) and carbon dioxide production rate (CO2) were measured continuously by electronic metabolic analyzers, with the treadmill speed and elevation increased at 3-min intervals. O2max was achieved when O2 reached a plateau value and the respiratory exchange ratio exceeded 1.0, or when the heart rate was within 95% of the girl’s age-predicted maximum.

Body composition measurement

A Hologic QDR-2000 instrument (Hologic, Inc., Waltham, MA) was used to assess FM and fat-free mass (FFM). The scanning software was appropriate for the weight range of our study subjects, and the accuracy of the FM measurements was independent of pubertal development (24).

Statistical analyses

{chi}-square was used to compare groups’ sexual maturity. Analysis of covariance was used to determine the effect of race on serum leptin concentrations while controlling for confounding variables. Bivariate correlation was used to determine the relationship of serum leptin concentrations with age, sexual maturity, body size, body fatness, and serum insulin concentrations. All statistical analyses were performed using SPSS for Windows, version 7.5.1 (SPSS, Inc., Chicago, IL).


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Age, sexual maturity, physical characteristics, body composition, and physical fitness of study subjects

As shown in Table 1Go, the African-American girls were older than the Caucasian girls. After adjusting for age, the weight, height, body mass index (BMI), FFM, FM, and serum insulin concentrations were significantly higher, but O2max was significantly lower, in the African-American girls than in the Caucasian girls.

Serum leptin comparison

After adjusting for age, the serum leptin concentrations (Table 2Go), expressed in absolute units, after logarithmic transformation and after normalization to FM, were significantly higher in the African-American girls than in the Caucasian girls. The racial difference in serum leptin concentrations persisted after controlling for serum insulin concentrations or when simultaneously controlling for differences in sexual maturity, FM, and O2max. Similar results were obtained when FM was estimated using the 4-compartment model based on measurements of body density, bone mineral content, and total body water.


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  		Table 2. Serum leptin concentrations of Caucasian and African-American subjects

 
In a smaller subset of 33 African-American and 29 Caucasian normal-weight (BMI: 20.9 ± 2.1 vs. 20.3 ± 1.5 kg/m2, P = 0.17) girls, who were matched for age (13.4 ± 1.7 vs. 14.0 ± 1.6 yr, P = 0.14), sexual maturity (pubic hair development, P = 0.22; breast development, P >= 0.18), body weight (54.9 ± 7.7 vs. 52.7 ± 6.4 kg, P = 0.24), height (161.8 ± 7.2 vs. 161.1 ± 6.9 cm, P = 0.69), FFM (37.2 ± 4.4 vs. 36.4 ± 4.4 kg, P = 0.5), and FM (15.4 ± 5.0 vs. 14.1 ± 3.4 kg, P = 0.21), the serum leptin concentrations remained significantly higher in the African-American girls than in the Caucasian girls (11.2 ± 6.4 vs. 7.4 ± 3.4 ng/mL, P < 0.02). The racial difference in serum leptin concentrations among this smaller group of normal-weight girls remained significant after adjusting for insulin concentration.

Relationship between serum leptin concentrations and other variables

Serum leptin concentrations were positively and significantly (P = 0.01) correlated with age (r = 0.23), Tanner stages of pubic hair development (r = 0.32), body weight (r = 0.79), BMI (r = 0.83), percent FM (r = 0.79), FM (r = 0.87), and serum insulin concentration (r = 0.55).


   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Serum leptin concentrations have been shown to correlate strongly with indexes of fatness in children (9, 18, 20, 25) and in adults (8, 10, 11, 12) and were better correlated with absolute FM than BMI or percent FM (19). Furthermore, serum leptin concentrations have been shown to increase with sexual development in girls (18, 21). Our results are in agreement with these observations.

Our data (Table 2Go) demonstrate significant differences in serum leptin concentrations between the African-American and Caucasian girls. The higher serum leptin concentrations in the African-American girls can be partially explained by the higher FM in these girls (Table 1Go). However, the difference persisted after leptin was normalized to FM, estimated using either the Hologic instrument or the four-compartment model. More importantly, the racial difference in serum leptin concentrations was observed in the smaller group of normal-weight African-American and Caucasian girls who were matched for age, sexual maturity, and FM.

These findings contrast with those of four other studies indicating no racial difference in serum leptin concentrations (9, 25, 26, 27). The inability to detect a significant racial difference in serum leptin concentrations in those studies was probably because of an insufficient number of study subjects, inclusion of boys in the analysis, and/or inappropriate time of blood collection. Serum leptin concentrations have been shown to increase continuously with sexual maturation in girls, but decline quickly in boys after 10 yr of age, when serum testosterone levels begin to rise (18, 21). Therefore, the inclusion of boys in the leptin analysis might have precluded the detection of a significant ethnic effect on serum leptin concentrations. In our study, serum samples were obtained in the morning, after a 12-h fast. Serum leptin concentrations have been shown to be highest between midnight and early morning hours, and lowest around noon to mid-afternoon (11). The inability to detect a significant ethnic difference in serum leptin concentrations in the Ellis et al. (27) study could be attributed to the low serum leptin concentrations at the time the samples were collected, midday after a 3-h fast.

Our results also contradict the report by Nicklas et al. (28) that serum leptin concentrations were 20% lower in obese postmenopausal African-American women than in obese postmenopausal Caucasian women. Peak circulating leptin concentrations have been recorded during the luteal phase of the spontaneous menstrual cycle, when serum progesterone reached maximal levels (29). Serum leptin concentrations have been shown to be 25% lower in postmenopausal women than in premenopausal women in one study (19), but no difference was observed in two other studies (30, 31). Therefore, cessation in the production of reproductive hormones in postmenopausal women cannot fully explain the difference between the findings reported by Nicklas et al. (28) and our findings, and this difference demands further investigation.

In our study, serum leptin concentrations were positively correlated with serum insulin concentrations, and the racial difference in serum leptin concentrations remained significant after controlling for serum insulin concentration. Although short-term insulin infusion had no effect on serum leptin concentrations (26, 32), long-term insulin infusion has been shown to increase leptin release in vivo and in vitro (32). Because African-American children and adolescents have been shown to have higher serum insulin-glucose ratios after a standard glucose challenge, compared with Caucasian subjects (33), the relationship between insulin and leptin deserves further investigation.

Because the serum leptin concentration has been shown to positively correlate with sexual maturation in girls in this and previous studies (18, 21), and a rise in the serum leptin concentration has been shown to precede a rise in sex hormones in girls (21), higher serum leptin concentrations might contribute to the earlier onset of puberty in African-American girls (17). If leptin indeed suppresses appetite and up-regulates thermogenesis, the higher serum leptin concentrations in the African-American girls might represent lower leptin sensitivity, to accommodate their accelerated growth, in comparison with Caucasian girls (13, 14, 15, 16). Further studies are needed to clarify the roles and mechanisms by which leptin may regulate sexual maturity and growth in children. Because sexual maturity, FM, and O2max accounted for approximately half of the difference in serum leptin concentrations between the two groups, it might be interesting to determine whether leptin production and/or clearance differ between African-American and Caucasian girls.


   Acknowledgments
 
The authors are indebted to the volunteers; to the staff of the Metabolic Research Unit, for meeting the needs of the subjects during the study; to Dr. J. Hoyle in the Pediatrics Department of Kelsey-Seybold West Clinic; to Dr. M. desVignes-Kendrick, Director of the City of Houston Health and Human Services Department; to Ms. X. Earlie, Director of Sciences of the Aldine Independent School District; to Ms. S. Wooten, Principal at the Teague Middle School; to Dr. B. Shargey, Dean of Instruction, and Ms. C. C. Collins, Principal at the High School for Health Professions; to Ms. K. Wallace, for subject recruitment; and to Ms. L. Loddeke for editorial assistance in the preparation of the manuscript.


   Footnotes
 
1 This work was supported, in part, with federal funds from the U.S. Department of Agriculture, Agricultural Research Service, under Cooperative Agreement No. 58–6250-6–001. Disclaimer: The contents of this publication do not necessarily reflect the views or policies of the U.S. Department of Agriculture, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Back

Received March 4, 1998.

Revised June 10, 1998.

Accepted June 22, 1998.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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