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FJ
EXPRESS SUMMARY ARTICLE The Full-length version of this article is also available, published online July 18, 2002 as doi:10.1096/fj.02-0077fje. |
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Academic Division of Child Health, School of Human Development, University Hospital, Queen’s Medical Centre, Nottingham, NG7 2UH;
* Division of Agricultural Sciences, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough LE212 5RD;
Department of Animal Sciences, University of Missouri, Columbia, Missouri, USA; and
Institute of Biochemistry, Food Science and Nutrition, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot, Israel
2Correspondence: Academic Division of Child Health, School of Human Development, University Hospital, Queen’s Medical Centre, Nottingham NG7 2UH, UK. E-mail: michael.symonds{at}nottingham.ac.uk
SPECIFIC AIMS
Our study examined the hypothesis that leptin administration would improve thermoregulation in the newborn lamb and that this effect may be mediated by altered uncoupling protein (UCP)1 abundance and function.
PRINCIPAL FINDINGS
1. Administration of leptin prevented the normal decline in colonic temperature over the first 2 days after birth (Fig. 1
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2. Over the first week of neonatal life, administration of leptin accelerated the loss of mRNA and protein for UCP1 in brown adipose tissue (Fig. 2
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3. At 7 days of age, colonic temperature was strongly correlated with mRNA abundance and thermogenic potential of UCP1 in leptin-treated, but not control lambs, indicating more effective utilization of UCP1 for heat production after leptin administration
4. Leptin had no effect on weight gain or adipose tissue deposition; at 1 day of age only, leptin mRNA abundance was positively correlated with adipose tissue weight
CONCLUSIONS AND SIGNIFICANCE
The major findings of our study are that over the first 48 h of neonatal life, leptin administration enhances thermoregulation (possibly as a result of enhanced lipolysis), which has been suggested to be a major regulator of UCP1 activity. The effect on colonic temperature appears to be an immediate effect observed even at the lower dose (i.e., 10 µg) of leptin injected. Over the first 7 days after birth, leptin promotes the loss of UCP1 from brown adipose tissue. We have therefore shown for the first time a potential role for leptin in the neonate. Leptin appears to have acute effects on temperature control that can be dissociated from leptin’s chronic effects on UCP abundance and mitochondrial activity.
Leptin and thermoregulation
Over the first day of life, administration of a low dose of leptin improved thermoregulation by preventing the postnatal decline in colonic temperature. This response occurred in the absence of an increase in the amount or thermogenic potential of UCP1 but was accompanied by a reduced incidence of shivering, thereby acting to improve thermal efficiency and prevent further loss of body temperature.
Birth is associated with the rapid activation and appearance of UCP1 in conjunction with stimulation of lipolysis. At the same time, plasma leptin decreases due to removal of the placenta as a source of leptin, and there is decreased leptin mRNA expression within adipose tissue of the newborn. In the present study, leptin administration not only delayed the rate of decline in colonic temperature, but also plasma NEFA. Maintenance of greater concentrations of NEFA after leptin treatment may therefore be indicative of a higher sympathetic activity and increased norepinephrine turnover contributing to an acute increase in unmasking of GDP binding sites on UCP1. Any effect of this type appears to be short-lived as no difference was observed 2 h postleptin infusion. Increased tissue perfusion has been reported after leptin administration, which, if occurring in brown adipose tissue, would enhance heat transfer around the body, thereby improving thermoregulation. After the second day of neonatal life, leptin administration did not cause any further rise in NEFA. This indicates that the potential stimulatory effect of leptin on sympathetic activity may be linked to the initial surge in catecholamines at birth.
Leptin and postnatal development
The time course over which UCP1 is gradually lost correlates with the gradual rise in plasma leptin and adipose tissue deposition and a decline in leptin mRNA abundance. As a consequence, the parallel loss of UCP1 and leptin mRNA that occurred in controls lambs between 1 and 7 days of age was accelerated after leptin administration. These results provideevidence that leptin has similar effects on leptin and UCP1 gene expression and it is only in adult rodents that these genes may be reciprocally regulated. Adult sheep and humans normally do not express UCP1. The effect of leptin on mitochondrial proteins appeared to be specific to the inner mitochondria as VDAC abundance (located on the outer membrane) was unaffected. All lambs exhibited a marked increase in adipose tissue deposition over the first week of life irrespective of leptin treatment. This is in contrast to findings in neonatal rat pups, in which leptin treatment had a negative effect on body weight gain and fat deposition, and in neonatal mice, which became anorexic.
In conclusion, treatment of neonatal lambs with leptin improved thermoregulation over the first 48 h of life. At the same time, chronic leptin administration promoted the loss of UCP1 in brown adipose tissue. These adaptations may be beneficial to the neonate in preventing adverse tissue metabolism in response to environmental challenges such as infection that can result in a severe pyrogenic reaction in the neonate.
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FOOTNOTES
1 To read the full text of this article, go to http://www.fasebj.org/cgi/doi/10.1096/fj.02-0077fje; to cite this article, use FASEB J. (July 18, 2002) 10.1096/fj.02-0077fje 
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