Different thermic effects of leptin in adolescent females with varying body fat content

Background & aims: Investigating the effect of leptin on energy expenditure in undernutrition might lead to a better understanding of the role of leptin in regulating body weight in humans. Methods: 73 underweight female adolescents with anorexia nervosa (AN) were compared with 23 healthy normal weight (nwC), and 9 overweight girls (OW); 37 AN were followed during 7 months of weight recovery. Resting energy expenditure (REE, by indirect calorimetry), body composition (fat mass, FM; lean tissue mass, LTM; by Dual-Energy X-Ray Absorptiometry) and plasma hormones of leptin and 3,5,3'-Triiodothyronine (T₃) were measured. Results: In underweight, leptin, T₃ and REE adjusted for lean tissue mass (REE_LTM) were decreased; in OW, FM and leptin were increased at unchanged T₃ and REE_LTM. There was a significant positive relation between FM and leptin at low and normal (AN, r² = 0.26; nwC, r² = 0.51, p < 0.001), but not at high adiposity. Leptin and REE_LTM were positively associated in underweight (r² = 0.14, p = 0.001) but not in normal or overweight subjects. T₃ was linearly related to REE_LTM over the whole range of adiposity (r² = 0.42, p < 0.001). With weight gain in AN (5.0 ± 3.5 kg) the relationship between leptin and REE_LTM changed toward the conditions seen in normal weight controls. Conclusions: At low adiposity the interrelated fall of leptin and REE reflect an adaptive mechanism to preserve body weight. High leptin production associated with excessive adiposity was without effect on metabolic adaptation.