Gender differences in leptin levels during puberty are related to the subcutaneous fat depot and sex steroids

Little is known about the influence of adiposity and hormone release on leptin levels in children and adolescents. We utilized criterion methods to examine the relationships among sex steroids, body composition (4 compartment), abdominal visceral and subcutaneous fat (magnetic resonance imagery), total subcutaneous fat (sum of 9 skinfolds), energy expenditure (doubly labeled water), aerobic fitness, and serum leptin levels in prepubertal and pubertal boys (n = 16; n = 13) and girls (n = 12; n = 15). The sum of skinfolds accounted for more variance in leptin levels of all girls [coefficient of determination (R-2) = 0.70, P < 0.001] and all boys (R-2 = 0.60, P < 0.001) than the total fat mass (girls, R-2 = 0.52, P < 0.001; boys, R-2 = 0.23, P < 0.001). Total energy expenditure, corrected for the influence of fat-free mass, correlated inversely with leptin (R-2 = 0.18, P = 0.02). Gender differences in leptin disappeared when corrected for sex steroid levels or the combination of adiposity and energy expenditure. In multiple regression, the sum of skinfolds and free testosterone and estrogen levels accounted for 74% of the variance in leptin levels. We conclude that serum leptin levels are positively related to subcutaneous adiposity but negatively related to androgen levels. Energy expenditure may be negatively related to leptin levels by reduction of the adiposity, or a common genetic factor may influence both the activity and serum leptin levels.