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Submitted on May 12, 2005
Accepted on July 7, 2005
Liggins Institute, University of Auckland and National Research Centre for Growth and Development, Auckland, New Zealand, Institute of Biochemistry, Food Science and Nutrition, the Hebrew University of Jerusalem, Israel
* To whom correspondence should be addressed. E-mail: m.vickers{at}auckland.ac.nz.
An adverse prenatal environment may induce long-term metabolic consequences, in particular obesity and insulin resistance. Although the mechanisms are unclear, this "programing" has generally been considered an irreversible change in developmental trajectory. Adult offspring of rats subjected to undernutrition during pregnancy develop obesity, hyperinsulinemia and hyperleptinemia, especially in the presence of a high fat diet. Reduced locomotor activity and hyperphagia contribute to the increased fat mass. Using this model of maternal undernutrition, we investigated the effects of neonatal leptin treatment on the metabolic phenotype of adult female offspring. Leptin treatment (rec-rat leptin, 2.5 µg/g/day, sc) from postnatal d3 to d13 resulted in a transient slowing of neonatal weight gain, particularly in programed offspring, and normalized caloric intake, locomotor activity, body weight, fat mass, and fasting plasma glucose, insulin and leptin concentrations in programed offspring in adult life in contrast to saline treated offspring of undernourished mothers who developed all these features on a high fat diet. Neonatal leptin had no demonstrable effects on the adult offspring of normally fed mothers. This study suggests that developmental metabolic programing is potentially reversible by an intervention late in the phase of developmental plasticity. The complete normalization of the "programed" phenotype by neonatal leptin treatment implies that leptin has effects that reverse the prenatal adaptations resulting from relative fetal undernutrition.
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