Serum leptin and weight reduction in female obesity

Leptin, an adipocyte-derived hormone, induces a decrease in food intake and increases energy expenditure via hypothalamic interactions. In animal models obesity can be caused by leptin deficiency or by a dysfunction of the hypothalamic leptin receptor. Using a radioimmunoassay for the determination of leptin in human serum, we measured serum leptin levels in 227 otherwise healthy normal weight (N = 78; body mass index = 16.1-27.7 kg/m2) or obese women (N = 149; body mass index = 27.8-56.7 kg/m2). Fifty-three subjects were followed over a period of 12 weeks under weight reduction (800 kcal/day) and a subgroup of 33 for another 13 weeks after termination of the diet. Body mass index and serum leptin concentrations were measured longitudinally and compared to female controls not under diet. Under baseline conditions, log serum leptin levels were positively related to body mass index with a best fit using a non-linear regression (p < 0.001), indicating an attenuated increase in serum leptin levels with high body mass index. No subgroup with low serum leptin levels could be identified. Weight reduction induced a rapid decrease in serum leptin levels within the first 3 weeks to levels significantly lower than in body mass index-matched controls under normal diet (p < 0.001). This pattern was consistent after 6 and 12 weeks. Serum leptin levels increased again after the end of the diet but remained significantly lower than in the controls despite unrestricted calorie intake over 7 weeks. The rapid and persistent decrease in serum leptin to lower levels than expected from matched controls may explain the pertinent difficulties of obese subjects to cope with weight reduction.