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Published on: November 1, 2019
Early postnatal overfeeding induces early chronic renal dysfunction in adult male rats
Farid Boubred1, Laurent Daniel, Christophe Buffat
1INSERM UMR608, Faculté de Pharmacie, Université de la Méditerranée, Marseille, France.
Insights
Early postnatal overfeeding in low birth weight infants significantly increases risks for adult hypertension and kidney dysfunction, especially in males. This "second hit" exacerbates reduced nephron numbers, leading to lasting vascular and renal damage.
Area of Science:
- Developmental programming
- Nephrology
- Vascular biology
Background:
- Low birth weight is linked to adult hypertension and renal dysfunction.
- Accelerated postnatal growth may worsen these outcomes.
- The specific impact of postnatal overfeeding on vascular and renal health is not well understood.
Purpose of the Study:
- To investigate the long-term vascular and renal effects of early postnatal overfeeding in appropriate and growth-restricted offspring.
- To determine the role of postnatal overfeeding as a contributing factor to hypertension and renal disease.
Main Methods:
- Induction of intrauterine growth restriction (IUGR) via maternal low-protein diet.
- Early postnatal overfeeding (OF) by reducing litter size in both normal birth weight (NBW+OF) and IUGR pups.
- Measurement of systolic blood pressure (SBP) and glomerular filtration rate (GFR) in young and aging offspring.
- Assessment of glomerulosclerosis and nephron number in aging offspring.
Main Results:
- Reduced nephron number was observed in male offspring with IUGR and IUGR+OF.
- Accelerated postnatal growth (OF) in IUGR males led to a 40% reduction in GFR by 12 months.
- Both NBW+OF and IUGR+OF aging male offspring exhibited sustained hypertension and glomerulosclerosis.
- Female offspring showed no significant alterations in SBP or renal function.
Conclusions:
- Early postnatal overfeeding acts as a critical
- second hit
- exacerbating the long-term renal and vascular consequences of intrauterine growth restriction.
- The detrimental effects of postnatal overfeeding are gender-dependent, primarily affecting males.
- This model highlights the significant, lasting impact of early life nutrition on adult health, particularly in the development of hypertension and renal disease.
Abstract:
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.

