The response of serum leptin to short (4 days) and prolonged (28 days)
energy restriction (50% reduction in energy intake) was determined in
18 (9 male, 9 female) moderately obese humans (body mass index 32.0+/
-0.6 kg/m(2) mean+/-SEM), 9 of whom had mild non-insulin-dependent dia
betes mellitus (NIDDM). Body composition was assessed before and at th
e end of the energy restriction using DEXA. The subjects lost a measur
ed 2.6+/-0.4 kg of body fat after 28 days and an estimated 0.3 kg at 4
days. Serum leptin fell to 64+/-3% of baseline levels at day 4 and fu
rther to 46+/-4% at day 28. In a multiple correlation analysis, the ch
ange in leptin concentration at day 4 was significantly related to the
change in dietary carbohydrate intake (partial r = 0.68, p < 0.005) b
ut not to changes in fat (r = 0.12) or protein (r = 0.02) intakes. The
re was a 1:1 relationship between the changes in leptin and dietary ca
rbohydrate (regression slope = 1.0+/-0.3). Gender, or the presence of
NIDDM had no effects on these responses. This pronounced fall in serum
leptin in association with reduced carbohydrate intake before substan
tial loss of body fat suggests a role for leptin in defending the body
's carbohydrate stores and implicates leptin in the satiating effects
of carbohydrate, Dietary or other interventions which maintain leptin
levels during weight reduction may lead to improvements in weight loss
.