Gene expression of leptin and uncoupling proteins: molecular end-points of fetal development.

Uncoupling proteins (UCPs) are considered to be major determinants of energy expenditure in mammals. During development in rodents, the expression of the UCP genes occurs sequentially. UCP2 mRNA is expressed long before birth. UCP1 mRNA expression in brown adipose tissue (BAT) starts in the late fetal period, and the expression of UCP3 mRNA begins immediately after birth in BAT and skeletal muscle. The postnatal induction of UCP1 gene expression is due mainly to cold stimuli, whereas the switch-on of UCP3 mRNA expression after birth requires the stimulus of food intake, specifically of lipids in the mother's milk. However, UCP3 mRNA expression after birth is also highly sensitive to leptin, and administration of a single injection of leptin to neonatal mice that were not allowed to suckle partly mimicked the natural induction of UCP3 gene expression in BAT and skeletal muscle. The speed of the effects of leptin on UCP3 mRNA expression suggests a direct action on skeletal muscle and BAT. The injection of leptin produced minor effects on UCP1 mRNA expression, and no effects were observed on UCP2 mRNA. In summary, leptin appears to contribute to the regulation of UCP3 gene expression in the perinatal period. Whatever the mechanism of action of leptin in BAT and skeletal muscle, it is already functional at birth.