The role of leptin in the transition from fetus to neonate

Leptin is a 16 kDa hormone which has been shown to have a major physiologic al role in the control of energy balance. Leptin is produced primarily in w hite adipose tissue, although there is evidence for its production in brown adipose tissue (BAT) and the placenta. BAT is critically important for the initiation of non-shivering thermogenesis in the newborn through the BAT-s pecific uncoupling protein (UCP), UCP1. This factor is particularly importa nt in lambs in which levels of UCP1 peak at birth, concomitant with a rapid decline in plasma leptin levels. Our studies have examined the effect of a cute and chronic administration of leptin to neonatal lambs, investigating effects on colonic temperature, UCP1 and thermogenic potential of BAT. Admi nistration of leptin in sequential physiological doses of 10, 100 and 100 m ug to neonatal lambs caused a modest increase in colonic temperature which was not observed in weight-matched vehicle-treated controls. This increase in colonic temperature was not mediated by an increase in either abundance or thermogenic potential of UCP1, as previously shown in adult rodents. UCP 1 mRNA levels were 30 % lower in leptin-treated lambs, which is also contra dictory to findings in adult rodents. Leptin treatment resulted in a dose-d ependent rise in plasma leptin, with levels at the end of the study being a lmost twenty times greater in leptin-treated animals. To determine whether these findings in neonatal lambs were transient due to the complex milieu o f hormones present after birth, we examined the effect of chronic leptin tr eatment over 6 d. Pairs of lambs were treated daily, from the second to sev enth day of life with 100 mug leptin or vehicle. Colonic temperatures of le ptin- and vehicle-treated animals remained similar throughout the study. UC P1 abundance was significantly lower in the leptin-treated animals, suggest ing that the drop in UCP1 mRNA seen in the previous study had been translat ed to protein levels. In conclusion, the decline in plasma leptin levels at birth may be a signal to initiate enteral feeding. In lambs, the rapid los s of UCP1 mRNA, which occurs within the first few days of life, appears to be accelerated by leptin administration, possibly stimulating the developme nt of white adipose tissue and generation of body heat through mechanisms o ther than non-shivering thermogenesis by UCP1 in BAT.