Leptin, an adipocyte-derived hormone, induces a decrease in food intak
e and increases energy expenditure via hypothalamic interactions. In a
nimal models obesity can be caused by leptin deficiency or by a dysfun
ction of the hypothalamic leptin receptor. Using a radioimmunoassay fo
r the determination of leptin in human serum, we measured serum leptin
levels in 227 otherwise healthy normal weight (N = 78; body mass inde
x = 16.1-27.7 kg/m(2)) or obese women (N = 149; body mass index = 27.8
-56.7 kg/m(2)). Fifty-three subjects were followed over a period of 12
weeks under weight reduction (800 kcal/day) and a subgroup of 33 for
another 13 weeks after termination of the diet. Body mass index and se
rum leptin concentrations were measured longitudinally and compared to
female controls not under diet. Under baseline conditions, log serum
leptin levels were positively related to body mass index with a best f
it using a non-linear regression (p < 0.001), indicating an attenuated
increase in serum leptin levels with high body mass index. No subgrou
p with low serum leptin levels could be identified. Weight reduction i
nduced a rapid decrease in serum leptin levels within the first 3 week
s to levels significantly lower than in body mass index-matched contro
ls under normal diet (p < 0.001). This pattern was consistent after 6
and 12 weeks. Serum leptin levels increased again after the end of the
diet but remained significantly lower than in the controls despite un
restricted calorie intake over 7 weeks. The rapid and persistent decre
ase in serum leptin to lower levels than expected from matched control
s may explain the pertinent difficulties of obese subjects to cope wit
h weight reduction.