Serum Immunoreactive-Leptin Concentrations in Normal-Weight and Obese Humans
Robert V. Considine, Ph.D., Madhur K. Sinha, Ph.D., Mark L. Heiman, Ph.D., Aidas Kriauciunas, Ph.D., Thomas W. Stephens, Ph.D., Mark R. Nyce, M.S., Joanna P. Ohannesian, B.S.N., Cheryl C. Marco, R.D., Linda J. McKee, M.H.S., Thomas L. Bauer, M.D., and José F. Caro, M.D.
Background Leptin, the product of the ob gene, is a hormonesecreted by adipocytes. Animals with mutations in the ob geneare obese and lose weight when given leptin, but little is knownabout the physiologic actions of leptin in humans.
Methods Using a newly developed radioimmunoassay, we measuredserum concentrations of leptin in 136 normal-weight subjectsand 139 obese subjects (body-mass index, >27.3 for men and>27.8 for women; the body-mass index was defined as the weightin kilograms divided by the square of the height in meters).The measurements were repeated in seven obese subjects afterweight loss and during maintenance of the lower weight. Theob messenger RNA (mRNA) content of adipocytes was determinedin 27 normal-weight and 27 obese subjects.
Results The mean (±SD) serum leptin concentrations were31.3±24.1 ng per milliliter in the obese subjects and7.5±9.3 ng per milliliter in the normal-weight subjects(P<0.001). There was a strong positive correlation betweenserum leptin concentrations and the percentage of body fat (r= 0.85, P<0.001). The ob mRNA content of adipocytes was abouttwice as high in the obese subjects as in the normal-weightsubjects (P = 0.005) and was correlated with the percentageof body fat (r = 0.68, P<0.001) in the 54 subjects in whomit was measured. In the seven obese subjects studied after weightloss, both serum leptin concentrations and ob mRNA content ofadipocytes declined, but these measures increased again duringthe maintenance of the lower weight.
Conclusions Serum leptin concentrations are correlated withthe percentage of body fat, suggesting that most obese personsare insensitive to endogenous leptin production.
Source Information
From the Divisions of Endocrinology and Metabolism (R.V.C., M.K.S., M.R.N., J.P.O., C.C.M., J.F.C.) and Clinical Pharmacology, Biostatistics Section (L.J.M.), Department of Medicine, and the Department of Surgery (T.L.B.), Jefferson Medical College of Thomas Jefferson University, Philadelphia; and Eli Lilly Research Laboratories, Indianapolis (M.L.H., A.K., T.W.S.).
Address reprint requests to Dr. Considine at Thomas Jefferson University, 1025 Walnut St., 813 College Bldg., Philadelphia, PA 19107.
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