Clinical implications of leptin and its potential humoral regulators in long-term low-calorie diet therapy for obese humans

Objective: To address the clinical implications of leptin and to re-examine the relationship between leptin and its potential humoral regulators such as insulin, nonesterified fatty acids (NEFA) and triiodothyronine (T3) in low-calorie diet (LCD) for obese humans. Design: Longitudinal study. Setting: University and foundation hospitals. Subjects: Ten obese men and 10 premenopausal obese women. Interventions: Five men and five women took 800 kcal/day LCD and another five men and five women took 1400 kcal/day balanced deficit diet (BDD) during 4 weeks. Results: Plasma leptin levels in the LCD group decreased more markedly (46.2 +/- 14.6 to 13.2 +/- 3.6 ng/ml) than that expected for the decrement in percentage fat (39.0 +/- 1.7 to 35.9 +/- 1.7%) and body mass index (BMI; 35.4 +/- 2.4 to 33.1 +/- 2.2 kg/m2), while that in the BDD group did not decrease significantly (14.9 +/- 3.5 to 13.4 +/- 2.8 ng/ml). The ratio of the decrease in leptin levels to that of BMI during the first week was significantly greater than that during the following 3 weeks (39.5 +/- 2.7 vs 29.3 +/- 2.1%, P = 0.017). The plasma insulin and T3 levels also fell substantially in the first week and continued to decrease during the entire course. Plasma leptin levels measured weekly in each subject were correlated well with insulin (r = 0.586, P = 0.0003) and T3 (r = 0.785, P = 0.0004). Multiple regression analyses after adjustment for the time course and BMI revealed that serum levels of T3 were independently correlated with plasma leptin levels (r = 0.928, P < 0.0001). The plasma NEFA level was markedly elevated during the first 2 weeks and decreased thereafter. Conclusions: A rapid fall in leptin during the first week of LCD, coordinated by insulin, T3 and NEFA, should be beneficial for responding to decreased energy intake. Inversely, in view of the powerful effect of leptin on energy dissipation, the present findings suggest the potential usefulness of leptin in combination with caloric restriction for the treatment of obesity.