DIURNAL AND ULTRADIAN RHYTHMICITY OF PLASMA LEPTIN - EFFECTS OF GENDER AND ADIPOSITY

Plasma leptin shows a nocturnal rise and a pulsatile pattern. This wor k was undertaken to determine the effects of gender and obesity on thi s pattern. Twenty-four-hour leptin profiles were evaluated in 31 subje cts [17 male, 14 female; age: 36 +/- 2 yr (mean +/- SEM); body mass in dex: 27.5 +/- 1.0 kg/m(2)]. Plasma leptin profiles were higher in obes e (body mass index > 27 kg/m(2)) than in lean subjects and higher in w omen than in men, regardless of fat mass. Leptin showed diurnal rhythm icity with peaks between 2200-0300 (median: 0120) and nadirs between 0 800 and 1740 (median: 1033). Spectral analysis revealed 2 components ( periodicities: 24 and 12 h) with higher relative amplitudes in lean th an in obese subjects. The relative diurnal amplitude also was higher i n men than in women, controlling for adiposity. Insulinemia, female se x, and age were negative determinants of diurnal rhythm relative ampli tude. Pulse analysis revealed 3.6 +/- 0.3 pulses/24 h, occurring mostl y 2-3 h after meals. Pulse frequency correlated negatively with fat ma ss and insulinemia (Spearman's r = -0.54 and -0.37, respectively; P < 0.05 for each). Thus, obesity is associated not only with higher lepti n levels but also with blunted diurnal excursions and dampened pulsati lity. This abnormal rhythmicity may contribute to leptin resistance in obesity. The significance of the sexual dimorphism in the diurnal amp litude is unclear, but it may be related to leptin's putative role as a metabolic signal to the reproductive axis.