Dissociation of serum leptin concentration and body fat content during long term dietary intervention in obese individuals

High serum leptin concentrations are observed in humans with high body fat content, indicating leptin resistance. Reducing leptin levels by lowering body fat could restore leptin sensitivity. Our study was designed to clarify the relationship between changes in body composition and circulating leptin during a long term hypocaloric diet. 12 obese women and 10 obese men were included in a 1000 kcal/day dietary intervention trial for 10 weeks. Body composition was measured by body impedance analysis and leptin by radioimmunoassay every 2 weeks. Body fat was reduced in females from 39.0 +/- 1.5 kg to 32.9 +/- 1.5 kg (p < 0.001) and in males from 30.4 +/- 1.4 kg to 26.3 +/- 1.3 kg (p < 0.005). Plasma leptin decreased in females from 38.07 +/- 4.17 ng/ml to 18.90 +/- 2.75 ng/ml (p < 0.001) and in males from 10.58 +/- 2.16 ng/ml to 6.33 +/- 1.25 ng/ml (p < 0.001). Non-linear regression analysis of leptin kinetics showed a comparable one-phase exponential decline (y = Span . e(-K . x) + Plateau) in females ((x) over bar +/- SEM: K = 0.48 +/- 0.01) and males (K = 0.60 +/- 0.01). Kinetics of body fat differed significantly from leptin data for females (K = 0.10 +/- 0.001, p < 0.001) but not for males (K = 0.27 +/- 0.02, p > 0.05). The leptin plateau was reached in both groups after 6 - 8 weeks and the fat plateau in men after 10 weeks. Compared to healthy controls, some obese individuals had higher absolute values of leptin, but seemed to have a relative leptin deficiency when leptin was adjusted to body mass index according to a nonlinear regression model of a large group of healthy women (n = 561) and men (n = 393). We conclude that during a long-term hypocaloric diet leptin uncouples from changes in body fat mass.