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This Article Full Text Full Text (PDF) All Versions of this Article: 297/4/F943    most recent 90704.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Boubred, F. Articles by Simeoni, U. PubMed PubMed Citation Articles by Boubred, F. Articles by Simeoni, U.

Early postnatal overfeeding induces early chronic renal dysfunction in adult male rats

¹INSERM UMR608, Faculté de Pharmacie, Université de la Méditerranée, ; ²Division of Neonatology, Hôpital la Conception, Assistance Publique-Hôpitaux de Marseille, and ; ³UPRES EA3281 and ; ⁴UPRES EA2193 Faculté de Médecine, Université de la Méditerranée, Marseille; and ; ⁵INSERM U652, Institut Biomédical des Cordeliers, Paris, France

Submitted November 23, 2008 ; accepted in final form July 31, 2009

Low birth weight is associated with an increased risk of hypertension and renal dysfunction at adulthood. Such an association has been shown to involve a reduction of nephron endowment and to be enhanced by accelerated postnatal growth in humans. However, while low-birth-weight infants often undergo catch-up growth, little is known about the long-term vascular and renal effects of accelerated postnatal growth. We surimposed early postnatal overfeeding (OF; reduction of litter size during the suckling period) to appropriate-birth-weight (NBW+OF) and intrauterine growth restriction (IUGR; IUGR+OF) pups, obtained after a maternal gestational low-protein diet. Blood pressure (systolic blood pressure; SBP) and renal function (glomerular filtration rate; GFR) were measured in young and aging offspring. Glomerulosclerosis and nephron number were determined in aging offspring (22 mo). Nephron number was reduced in both IUGR and IUGR+OF male offspring (by 24 and 26%). GFR was reduced by 40% in 12-mo-old IUGR+OF male offspring, and both NBW+OF and IUGR+OF aging male offspring had sustained hypertension (+25 mmHg) and glomerulosclerosis, while SBP and renal function were unaffected in IUGR aging offspring. Female offspring were unaffected. In conclusion, in this experimental model, early postnatal OF in the neonatal period has major long-lasting effects. Such effects are gender dependent. Reduced nephron number alone, associated with IUGR, may not be sufficient to induce long-lasting physiological alterations, and early postnatal OF acts as a "second hit." Early postnatal OF is a suitable model with which to study the long-term effects of postnatal growth in the pathogenesis of vascular disorders and renal disease.

nephrogenesis; nephron number; catch-up growth; hypertension; glomerulosclerosis; developmental origins of adult diseases; low birth weight