Leptin and body weight regulation in patients with anorexia nervosa before and during weight recovery

Background: Leptin has been considered a starvation hormone, but its role in malnourished patients is unknown. Objective: We aimed to characterize the role of leptin in metabolic adaptation in women with anorexia nervosa (AN). Design: In a cross-sectional study, 57 women with AN [mean (+/-SD) body mass index (kg/m2) on admission: 15.2 +/- 1.5] were compared with 49 healthy, normal-weight women (mean body mass index: 22.3 +/- 2.3). Nineteen patients were reinvestigated during weight gain 43 and 84 d after baseline. We measured serum concentrations of leptin, soluble leptin receptor, insulin, ghrelin, and thyroid hormones [thyrotropin, triiodothyronine (T3), and thyroxine]; fat mass (FM) and fat-free mass (FFM); resting energy expenditure (REE); energy intake; and eating behavior. Results: Compared with values in the control women, leptin, T3, REE, FM, and FFM were lower in the women with AN, but the leptin secretion rate was not significantly different. Leptin correlated with FM (r = 0.83, P < 0.001), T3 (r = 0.68, P < 0.001), respiratory quotient (r = -0.47, P < 0.001), and REE (r = 0.58, P < 0.001). The association with REE weakened after adjustment for FFM and disappeared after further adjustment for T3. Hunger and appetite had positive, whereas satiety and restraint had negative, associations with leptin. During weight gain (9.0 +/- 3.3 kg in 84 d), serum leptin and the leptin secretion rate increased. Changes in leptin secretion were associated with energy intake and REE. The initial changes in the leptin secretion rate (ie, the difference between baseline and 43 d) were negatively associated with changes in body weight from 43 to 84 d. Conclusions: Leptin contributes to metabolic adaptation in women with AN. The leptin response is associated with weight gain.