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Diurnal and Ultradian Dynamics of Serum Adiponectin in Healthy Men: Comparison with Leptin, Circulating Soluble Leptin Receptor, and Cortisol Patterns

Division of Endocrinology and Metabolism (A.G., J.L.C., C.S.M.) and Division of Cardiology/Margret and H. A. Rey Laboratory for Nonlinear Dynamics in Medicine (C.-K.P., J.E.M., A.L.G.), Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215

Address all correspondence and requests for reprints to: Christos S. Mantzoros, M.D., Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center, 99 Brookline Avenue, RN 325A, Boston, Massachusetts 02215. E-mail: cmantzor{at}caregroup.harvard.edu.

Adiponectin is an abundant serum adipokine secreted exclusively from differentiated adipocytes, which plays an important role in regulating insulin sensitivity. The dynamics of circulating adiponectin concentrations have yet to be systematically investigated. We sought to determine whether serum adiponectin levels exhibit diurnal or ultradian rhythms in healthy normal-weight men and to compare the 24-h profile of adiponectin fluctuations with those of leptin, leptin-binding protein (sOB-R), and cortisol.

We collected blood samples at 15-min intervals over 24 h from six subjects receiving an isocaloric diet, and we measured adiponectin, leptin, sOB-R, and cortisol levels. Fourier and cross-correlation analyses were performed on these time series to study diurnal variations, and the Cluster7 program was used for pulsatility analysis.

Circulating adiponectin and sOB-R levels exhibited ultradian pulsatility as well as a diurnal variation with a significant decline at night, reaching a nadir in the early morning. The 24-h variations of serum adiponectin and sOB-R were nearly identical and followed those of cortisol after a few hours, but were out-of-phase with leptin diurnal rhythms. These data suggest that adiponectin and sOB-R levels might be influenced by common regulatory factors and challenge the notion that cortisol may have a direct inhibitory effect on adiponectin in humans.

This study was supported by National Institute of Diabetes Digestive and Kidney Diseases Grant DK58785, National Institutes of Health (NIH) Grant K30 HL04095, NIH Grant MO1-RR01032, NIH/National Center for Research Resources Grant P41-RR13622, NIH/National Institute on Aging Grant P60-AG08812, the G. Harold and Leila Y. Mathers Charitable Foundation, and the Centers for Disease Control and Prevention Grant H75-CCH119124.

Abbreviations: CV, Coefficient of variation; sOB-R, soluble leptin receptor.

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