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Unité de Neurosciences et Physiologie Adaptatives (F.D., C.B., M.E., I.D.-C., C.L., J.L., Equipe dénutritions maternelles périnatales, Equipe Associeé (EA) 4052, Université des Sciences et Technologies de Lille, 59655 Villeneuve dAscq Cédex, France; and Université de Franche-Comté (P.-Y.R.), Faculté de Médecine et de Pharmacie, EA 3922, Institut Fédératif de Recherche 133, 25000 Besançon, France
Address all correspondence and requests for reprints to: Didier Vieau, Ph.D., Unité de Neurosciences et Physiologie Adaptatives, Equipe Associée 4052, Bâtiment SN4, 2ème étage, Université des Sciences et Technologies de Lille, 59655 Villeneuve dAscq Cédex, France. E-mail: didier.vieau{at}univ-lille1.fr.
A growing body of evidence suggests that maternal undernutrition sensitizes the offspring to the development of energy balance metabolic disorders such as type 2 diabetes, dyslipidemia, and obesity. The present study aimed at examining the impact of maternal undernutrition on leptin plasma levels in newborn male rats and on the arcuate nucleus proopiomelanocortin (POMC) and neuropeptide Y (NPY) neurons that are major leptin targets. Using a model of perinatal maternal 50% food-restricted diet (FR50) in the rat, we evaluated leptin plasma levels and hypothalamic POMC and NPY gene expression from postnatal day (PND) 4 to PND30 in both control and FR50 offspring. In control rats, a postnatal peak of plasma leptin was observed between PND4 and PND14 that reached a maximal value at PND10 (5.17 ± 0.53 ng/ml), whereas it was dramatically reduced in FR50 pups with the higher concentration at PND7 (0.93 ± 0.23 ng/ml). In FR50 animals, using semiquantitative RT-PCR and in situ hybridization, we showed that the hypothalamic POMC mRNA level was decreased from PND14 until PND30, whereas NPY gene expression was not significantly modified. In PND21 FR50 animals, we observed strikingly reduced immunoreactive β-endorphin nerve fibers projecting to the hypothalamic paraventricular nucleus without affecting NPY projections. Our data showed that maternal undernutrition drastically reduces the postnatal surge of plasma leptin, disturbing particularly the hypothalamic wiring as well as the gene expression of the anorexigenic POMC neurons in male rat pups. These alterations might contribute to the adult metabolic disorders resulting from perinatal growth retardation.
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