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The Suprachiasmatic Nucleus Generates the Diurnal Changes in Plasma Leptin Levels

Netherlands Institute for Brain Research (A.K., S.E.L.F., J.W., R.M.B.), and Department of Endocrinology and Metabolism, F5–171 (E.F., O.B.), and Department of Clinical Chemistry, Laboratory of Endocrinology (E.E.), Academic Medical Center, 1105 AZ Amsterdam; and Department of Endocrinology C4-R, Leiden University Medical Center (J.A.R.), 2300 RC Leiden, Amsterdam

Address all correspondence and requests for reprints to: Dr. A. Kalsbeek, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam, The Netherlands. E-mail: a.kalsbeek{at}nih.knaw.nl

At present it is not clear which factors are responsible for the diurnal pattern of plasma leptin levels, although the timing of food intake and circulating hormones such as glucocorticoids and insulin have both been proposed as independent determinants. In this study we show that ablation of the biological clock by thermal lesions of the hypothalamic suprachiasmatic nucleus (SCN) completely eliminates the diurnal pattern of plasma leptin levels. By contrast, removal of the diurnal corticosterone signal by adrenalectomy and corticosterone replacement did not affect diurnal plasma leptin levels. More importantly, removal of the nocturnal feeding signal by submitting the animals to a regular feeding schedule of six meals per day did not abolish the diurnal plasma leptin levels. However, both SCN lesions and the regular feeding schedule did cause an increase in the 24-h mean plasma leptin levels. As neither rhythmic feeding, insulin, or corticosterone signals can completely explain the diurnal plasma leptin rhythm, we conclude that biological clock control of the sympathetic input to the adipocyte is essential for regulation of the daily rhythm in leptin release.

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