At present it is not clear which factors are responsible for the diurnal pa
ttern of plasma leptin levels, although the timing of food intake and circu
lating hormones such as glucocorticoids and insulin have both been proposed
as independent determinants. In this study we show that ablation of the bi
ological clock by thermal lesions of the hypothalamic suprachiasmatic nucle
us (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 t
he animals to a regular feeding schedule of six meals per day did not aboli
sh the diurnal plasma leptin levels. However, both SCN lesions and the regu
lar feeding schedule did cause an increase in the 24-h mean plasma leptin l
evels. As neither rhythmic feeding, insulin, or corticosterone signals can
completely explain the diurnal plasma leptin rhythm, we conclude that biolo
gical clock control of the sympathetic input to the adipocyte is essential
for regulation of the daily rhythm in leptin release.