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Sex Differences in Circulating Human Leptin Pulse Amplitude: Clinical Implications¹

Clinical Neuroendocrinology Branch, National Institute of Mental Health (J.L., A.B.N., M.-L.W., P.B.B., P.P.N., A.M., P.W.G.), and the Warren Grant Magnuson Clinical Center (L.C.), National Institutes of Health, Bethesda, Maryland 20892; the Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School (C.M., V.K., J.S.F.), Boston, Massachusetts 02215; the Department of Internal Medicine, and National Science Foundation Center for Biological Timing, University of Virginia Health Sciences Center (J.V.D.), Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: Julio Licinio, M.D., Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Building 10/2D46, 10 Center Drive, MSC 1284, Bethesda, Maryland 20892-1284. E-mail: licinio{at}nih.gov

Leptin, a product of fat cells, provides a signal of nutritional status to the central nervous system. Leptin concentrations have ultradian and diurnal fluctuations. We conducted this study to assess sex differences in the levels of organization of frequently sampled leptin concentrations in healthy, normal weight women and men. Leptin levels were sampled every 7 min for 24 h in 14 healthy, normal weight individuals (6 women and 8 men). The 14 leptin time series containing a total of 2898 leptin measurements were assessed by 1) algorithms that characterize statistically significant pulsatility, 2) Spectral (Fourier) analysis, 3) analysis of time intervals and variability, and 4) approximate entropy. We found that frequently sampled plasma leptin concentrations have a 24-h profile that is numerically more than twice as high in women as in men, and leptin pulse amplitude is likewise more than twice as high in women. However, healthy men and women have nearly identical concentration-independent and frequency-related 24-h and ultradian patterns. Leptin concentrations have nonrandom fluctuations over 24 h, independent of their absolute value and underlying 24-h periodicity, that are similar in men and women. Ultradian periodicities detected by Fourier time series have similar values in men and women. The strongest distinction between the sexes in the level of organization of leptin concentration is not at the level of pulse organization or oscillation frequency, but, rather, in the mass or amount of leptin released (or removed) per unit time, indicating that women might be more resistant to the effects of leptin than men. Because leptin is clinically relevant to the regulation of body weight, future studies should examine whether the relative leptin resistance exhibited by women might contribute to their increased susceptibility to disorders whose pathophysiology involves dysregulation of food intake and body weight.

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