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Neonatal leptin treatment reverses developmental programming

Vickers, M.H., Gluckman, P.D., Coveny, A.H., Hofman, P.L., Cutfield, W.S., Gertler, A., Breier, B.H. and Harris, M. (2005) Neonatal leptin treatment reverses developmental programming Endocrinology, 146, (10), pp. 4211-4216. (doi:10.1210/en.2005-0581).

Record type: Article


An adverse prenatal environment may induce long-term metabolic consequences, in particular obesity and insulin resistance. Although the mechanisms are unclear, this programming 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·d, sc) from postnatal d 3–13 resulted in a transient slowing of neonatal weight gain, particularly in programmed offspring, and normalized caloric intake, locomotor activity, body weight, fat mass, and fasting plasma glucose, insulin, and leptin concentrations in programmed 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 programming is potentially reversible by an intervention late in the phase of developmental plasticity. The complete normalization of the programmed phenotype by neonatal leptin treatment implies that leptin has effects that reverse the prenatal adaptations resulting from relative fetal undernutrition.

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Published date: 2005


Local EPrints ID: 40622
ISSN: 0013-7227
PURE UUID: eb2616d6-1e57-4037-b8e1-1d6e19613b6c

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Date deposited: 06 Jul 2006
Last modified: 16 Apr 2017 21:51

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Author: M.H. Vickers
Author: P.D. Gluckman
Author: A.H. Coveny
Author: P.L. Hofman
Author: W.S. Cutfield
Author: A. Gertler
Author: B.H. Breier
Author: M. Harris

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