Effect of prolonged moderate and severe energy restriction and refeeding on plasma leptin concentrations in obese women

Background: Plasma leptin in humans is subject to both long and short-term regulation; it correlates with indexes of body fat that can only change slo wly. However, short-term fasting causes large and rapid decreases. Objective: We tested the interactions between energy intake and fat loss on plasma leptin during prolonged moderate and severe energy restriction, wit h a view to understanding mechanisms of control. Design: Postabsorptive leptin was measured with an enzyme-linked immunosorb ent assay specific for the human peptide in 21 obese women aged 41 +/- 3 y (weight: 102 +/- 4 kg; 48 +/- 1% body fat) after 1 wk of a weight-maintaini ng diet and then weekly for 4 wk during a total fast (group 1); a 1.9-MJ/d all-protein, very-low-energy diet (VLED) (group 2); or a low-energy, balanc ed-deficit diet (BDD) providing 50% of maintenance energy (group 3). In gro ups 1 and 2, leptin was also measured after 1 wk of refeeding with a diet e quivalent to the BDD. Results: Mean leptin decreased markedly by up to 66% (P < 0.001) at week 1 of energy restriction and then gradually thereafter. The change in leptin p er kilogram fat mass correlated with that in glucose concentrations [r = 0. 538 (P = 0.012) at week 1 and r = 0.447 (P = 0.042) at week 4] but not with that in fat mass. During refeeding postfasting, leptin increased (P = 0.00 8), despite an ongoing loss of fat mass and correlated positively with chan ges in resting energy expenditure. At times with comparable cumulative ener gy restriction and fat loss between diets, the percentage change in leptin paralleled that in glucose. Conclusions: In obesity, changes in energy intake over days to weeks are a primary modulator of plasma leptin concentrations that are related to the c hange in glycemia and are able to override the regulatory influence of fat mass.