POSTNATAL LEPTIN SURGE AND REGULATION OF CIRCADIAN-RHYTHM OF LEPTIN BY FEEDING - IMPLICATIONS FOR ENERGY HOMEOSTASIS AND NEUROENDOCRINE FUNCTION

Leptin is thought to regulate energy balance through effects on food i ntake and thermogenesis. In addition, leptin may serve as a mediator o f the neuroendocrine response to starvation, and may modulate the stre ss response and the timing of puberty, A role for leptin in developmen t is suggested by the presence of neuroendocrine and structural neuron al abnormalities in ob/ob mice with genetic leptin deficiency. Here, w e sought to determine the ontogeny of leptin expression and its relati onship to the developing neuroendocrine axis. Leptin increased 5-10-fo ld in female mice during the second postnatal week independent csf fat mass, and declined after weaning, The rise in leptin preceded the est ablishment of adult levels of corticosterone, thyroxine, and estradiol , In contrast to adult mice, leptin was not acutely regulated by food deprivation during the early postnatal period, Circadian rhythms of le ptin, corticosterone, and thyroxine were regulated by food intake in a dult mice. When ad libitum feeding was restricted to the light cycle, peak corticosterone levels were shifted to the beginning of the light cycle and coincided with the nadir of leptin. The inverse relationship between leptin and corticosterone was maintained such that a rise in leptin after feeding was associated with a decline in corticosterone. To determine whether changes in corticosterone during food restriction are mediated by leptin, we compared the patterns of corticosterone le vels among ob/ob, db/db and lean mice, Despite their higher basal leve ls of corticosterone, Ieptin deficiency in ob/ob mice did not prevent the nocturnal rise in corticosterone. In contrast, the nocturnal surge of corticosterone was blunted in db/db mice, Therefore, it is likely that factors in addition to leptin are involved in the regulation of t he circadian rhythm of corticosterone, The temporal relationship betwe en leptin and other hormones in neonatal and adult mice suggests that leptin is involved in the maturation and function of the neuroendocrin e axis.