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.

Related Concept Videos