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Temporal Patterns of Circulating Leptin Levels in Lean and Obese Adolescents: Relationships to Insulin, Growth Hormone, and Free Fatty Acids Rhythmicity¹

Department of Pediatrics and the Yale Children’s Clinical Research Center, Yale University School of Medicine, New Haven, Connecticut 06510

Address correspondence and requests for reprints to: Sonia Caprio, M.D., Department of Pediatrics, 333 Cedar Street, Yale University School of Medicine, New Haven, Connecticut 06520. E-mail: Sonia.Caprio{at}Yale.edu

Alterations in nutritional status, such as obesity, markedly influence insulin, leptin, GH secretion, and free fatty acid (FFA) levels. We measured every hour for 24 h circulating leptin, insulin, GH, and FFA levels in lean and obese adolescents to determine: 1) the impact of adolescent obesity on the diurnal changes in leptin concentrations; and 2) the temporal relationships between the diurnal patterns of circulating leptin levels and insulin, GH, and FFA levels. During puberty, we found that the 24-h profile of circulating plasma leptin levels follows a bimodal pattern with minimal concentrations occurring early in the afternoon and a nocturnal elevation starting after midnight and culminating early morning. The time course of the diurnal variation in leptin levels in the obese adolescents was not different from that in lean controls. Of note, however, in obese girls leptin 24-h excursion and leptin night to day ratio were lower than those found in lean girls. In obese adolescents, mean GH levels varied significantly less during the day and night than lean controls. During the day, there were distinct preprandial increases and postprandial decreases in FFA levels, whereas after midnight FFA levels rose in both lean and obese adolescents. A significant positive correlation was found between mean plasma insulin levels between 0800 h and 2000 h and peak in leptin in lean and obese girls and boys (r = 0.63, P < 0.001). Peak leptin was inversely correlated with the area under the nocturnal GH levels in all groups (r = -0.31, P < 0.0003), whereas it was positively correlated with the nocturnal peak in FFA levels (r = 0.45, P < 0.004). In summary, we report in obese adolescent girls a blunted relative diurnal excursion in leptin levels. This abnormal rhythmicity may, in part, explain their leptin resistance state. The nocturnal rise in leptin was paralleled by a nocturnal rise in GH and FFA levels. Additional studies are needed to test the potential link between the adipose-derived peptide and GH axis in humans.

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