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 physiological role in the control of energy balance. Leptin is produced primarily in white 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-specific uncoupling protein (UCP), UCPI. This factor is particularly important 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 acute and chronic administration of leptin to neonatal lambs, investigating effects on colonic temperature, UCP1 and thermogenic potential of BAT. Administration of leptin in sequential physiological doses of 10, 100 and 100 microg 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 UCPI, as previously shown in adult rodents. UCP1 mRNA levels were 30 % lower in leptin-treated lambs, which is also contradictory to findings in adult rodents. Leptin treatment resulted in a dose-dependent rise in plasma leptin, with levels at the end of the study being almost twenty times greater in leptin-treated animals. To determine whether these findings in neonatal lambs were transient due to the complex milieu of hormones present after birth, we examined the effect of chronic leptin treatment over 6 d. Pairs of lambs were treated daily, from the second to seventh day of life with 100 microg leptin or vehicle. Colonic temperatures of leptin- and vehicle-treated animals remained similar throughout the study. UCP1 abundance was significantly lower in the leptin-treated animals, suggesting that the drop in UCP1 mRNA seen in the previous study had been translated 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 loss of UCP1 mRNA, which occurs within the first few days of life, appears to be accelerated by leptin administration, possibly stimulating the development of white adipose tissue and generation of body heat through mechanisms other than non-shivering thermogenesis by UCP1 in BAT.
Mostyn
A
A
Academic Division of Child Health, School of Human Development, University Hospital, Nottingham, UK. mgxam2@nottingham.ac.uk
Keisler
D H
DH
Webb
R
R
Stephenson
T
T
Symonds
M E
ME
D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins; D004305:Dose-Response Relationship, Drug; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007473:Ion Channels; D020738:Leptin / Q000008:administration & dosage* / Q000097:blood / Q000502:physiology*; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger / Q000378:metabolism; D012756:Sheep; D022722:Thermogenesis; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1