Plasma Leptin Levels in Healthy Children and Adolescents: Dependence on Body Mass Index, Body Fat Mass, Gender, Pubertal Stage, and Testosterone*

Abstract

Leptin, the product of the ob gene, is thought to play a key role in the regulation of body fat mass. Beyond this function, it appears to be an integral component of various hypothalamo-pituitary-endocrine feedback loops. Because childhood and puberty are periods of major metabolic and endocrine changes, leptin levels and various hormonal parameters were investigated in a large cohort of healthy children and adolescents (312 males, 401 females, age 5.8-19.9 yr). For this purpose, a specific and sensitive RIA was developed that allowed the accurate measurement of low leptin levels in young lean children. With this assay, leptin proved to be a comparatively stable protein under common conditions of blood sampling and storage. Leptin levels increased in girls with age (r = 0.47, P < 0.0001), but decreased in boys (r = -0.34, P < 0.0001). An analysis according to pubertal stage showed a steady increase in girls between 2.51 micrograms/L (median) at Tanner stage 1 to 6.24 micrograms/L at Tanner stage 5. In boys, leptin levels were highest at Tanner stage 2 (2.19 micrograms/L) and declined thereafter to 0.71 microgram/L at Tanner stage 5. A strong exponential relationship was observed for leptin levels with body mass index (BMI) and percentage body fat as determined by bioelectric impedance measurements in a subgroup of subjects. This relationship was similar between boys and girls at Tanner stages 1 and 2. In boys, there was a significant decline of leptin at a given BMI with further progression of puberty that was much less pronounced in girls. Although the relative increase of leptin with BMI and percent body fat was the same in both genders, the absolute values at a given BMI or percent body fat were significantly lower in boys in late puberty and in adolescents. In boys, but not in girls, there was an inverse correlation with testosterone concentrations (r = -0.43, P < 0.0001), which explained 10.5% of the variation of leptin levels in a multiple regression model. Since BMI proved to be the major influencing variable, reference ranges were constructed using a best-fit regression line of the form leptin = a*e(b*BMI) and stratifying ranges according to gender and pubertal stage. In conclusion, these data suggest that 1) plasma leptin levels increase in girls and decrease in boys after Tanner stage 2 as the pubertal development proceeds; 2) they show a significant gender difference especially in late puberty and adolescence, even after adjustment for BMI or percent body fat; 3) the lower levels in males may be explained at least in part by a suppressive effect of androgens; 4) reference ranges with BMI as the independent variable should be stratified according to gender and pubertal stage.

Correlation between birth weight, leptin, zinc and copper levels in maternal and cord blood

“…This association may reflect either a simple relationship with adipose tissue mass or an active role for leptin in fetal growth. Cord leptin concentration correlates closely with birth weight in term newborn infants at birth; infants who are large-for-date have high concentrations of leptin, and infants with intrauterine growth retardation (IUGR) have low concentrations of leptin (3,4,16,31,33). Cord leptin levels are decreased by conditions that lead to low birth weight, such as maternal smoking and prematurity (21).…”

Relationship between IGF-I Concentration and Metabolic Profile in Children with Growth Hormone Deficiency: The Influence of Children’s Nutritional State as well as the Ghrelin, Leptin, Adiponectin, and Resistin Serum Concentrations

“…Leptin is strongly correlated with the body mass [17], and at the level of the hypothalamus, it inhibits the appetite; thus, its action is opposed to ghrelin action [18]. Leptin also increases hepatic gluconeogenesis and muscle fatty acid oxidation [19].…”

Central Melanocortins and the Regulation of Weight During Acute and Chronic Disease

“…In normal infants, school-aged children, and adolescents, the normative range of serum leptin varies with age and becomes sexually dimorphic during adolescence. Within groups matched for age and gender, leptin levels are directly proportional to body fat mass, as reflected in the calculated body mass index (BMI) or measured with other methods (Blum et al, 1997;Clayton et al, 1997;Roemmich and Rogol, 1999). Given that elevations in circulating leptin would normally result in anorexia and weight loss, the elevated leptin concentrations consistently found in obese individuals have been interpreted as an indication of leptin resistance (Considine et al, 1996).…”