SERUM IMMUNOREACTIVE LEPTIN CONCENTRATIONS IN NORMAL-WEIGHT AND OBESEHUMANS

Background. Leptin, the product of the ob gene, is a hormone secreted by adipocytes, Animals with mutations in the ob gene are obese and los e weight when given leptin, but little is known about the physiologic actions of leptin in humans. Methods. Using a newly developed radioimm unoassay, we measured serum concentrations of leptin in 136 normal-wei ght subjects and 139 obese subjects (body-mass index, greater than or equal to 27.3 for men and greater than or equal to 27.8 for women; the body-mass index was defined as the weight in kilograms divided by the square of the height in meters). The measurements were repeated in se ven obese subjects after weight loss and during maintenance of the low er weight. The ob messenger RNA (mRNA) content of adipocytes was deter mined in 27 normal-weight and 27 obese subjects. Results. The mean (+/ -SD) serum leptin concentrations were 31.3+/-24.1 ng per milliliter in the obese subjects and 7.5+/-9.3 ng per milliliter in the normal-weig ht subjects (P < 0.001). There was a strong positive correlation betwe en serum leptin concentrations and the percentage of body fat (r = 0.8 5, P < 0.001). The ob mRNA content of adipocytes was about twice as hi gh in the obese subjects as in the normal-weight subjects (P = 0.005) and was correlated with the percentage of body fat (r = 0.68, P < 0.00 1) in the 54 subjects in whom it was measured. In the seven obese subj ects studied after weight loss, both serum leptin concentrations and o b mRNA content of adipocytes declined, but these measures increased ag ain during the maintenance of the lower weight. Conclusions. Serum lep tin concentrations are correlated with the percentage of body fat, sug gesting that most obese persons are insensitive to endogenous leptin p roduction. (C) 1996, Massachusetts Medical Society.