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Diurnal and Ultradian Rhythmicity of Plasma Leptin: Effects of Gender and Adiposity¹

The Department of Medicine (M.F.S., M.G.R.-G., A.K., A.S., R.M., S.D.J., R.B.), University of Southern California Medical School, Los Angeles, California 90033; and Joslin Diabetes Center (G.M.S.), Boston, Massachusetts 02215

Address all correspondence and requests for reprints to: Mohammed F. Saad, M.D., Division of Endocrinology and Diabetes, University of Southern California Medical School, 1200 North State Street, Unit I, P.O. Box 710, Los Angeles, California 90033. E-mail: saad{at}hsc.usc.edu

Plasma leptin shows a nocturnal rise and a pulsatile pattern. This work was undertaken to determine the effects of gender and obesity on this pattern. Twenty-four-hour leptin profiles were evaluated in 31 subjects [17 male, 14 female; age: 36 ± 2 yr (mean ± SEM); body mass index: 27.5 ± 1.0 kg/m²]. Plasma leptin profiles were higher in obese (body mass index > 27 kg/m²) than in lean subjects and higher in women than in men, regardless of fat mass. Leptin showed diurnal rhythmicity with peaks between 2200–0300 (median: 0120) and nadirs between 0800 and 1740 (median: 1033). Spectral analysis revealed 2 components (periodicities: 24 and 12 h) with higher relative amplitudes in lean than in obese subjects. The relative diurnal amplitude also was higher in men than in women, controlling for adiposity. Insulinemia, female sex, and age were negative determinants of diurnal rhythm relative amplitude. Pulse analysis revealed 3.6 ± 0.3 pulses/24 h, occurring mostly 2–3 h after meals. Pulse frequency correlated negatively with fat mass and insulinemia (Spearman’s r = -0.54 and -0.37, respectively; P < 0.05 for each). Thus, obesity is associated not only with higher leptin levels but also with blunted diurnal excursions and dampened pulsatility. This abnormal rhythmicity may contribute to leptin resistance in obesity. The significance of the sexual dimorphism in the diurnal amplitude is unclear, but it may be related to leptin’s putative role as a metabolic signal to the reproductive axis.

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