Aging-related sex-dependent loss of the circulating leptin 24-h rhythm in the rhesus monkey

The adipocyte-derived hormone leptin plays a pivotal role in the regulation of body weight and energy homeostasis. Many studies have indicated that the circulating levels of leptin show a 24-h rhythm, but the exact cause and nature of this rhythm is still unclear. In the present study, we remotely collected blood samples every hour from young and old, male and female rhesus monkeys, and examined their 24-h plasma leptin profiles. In both the young males (10-11 years) and females (7-13 years), a clear 24-h plasma leptin rhythm was evident with a peak occurring approximately 4 h into the night and a nadir occurring approximately 1 h into the day (lights on from 0700 to 1900 h). A 24-h plasma leptin rhythm was also observed in the old males (23-30 years), even when they were maintained under constant lighting conditions (continuous dim illumination of approximately 100 lx). In marked contrast, plasma leptin concentrations were relatively constant across the day and night in old peri- and post-menopausal females (17-24 years), regardless of the lighting schedule. These data establish that rhesus monkeys, like humans, show a daily nocturnal rise in plasma leptin, and the magnitude of this rhythm undergoes a sex-specific aging-dependent attenuation. Furthermore, they suggest that the underlying endocrine mechanism may be driven in part by a circadian clock mechanism.