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Hepatic structural alteration in adult programmed offspring (severe maternal protein restriction) is aggravated by

Vanessa Souza-Mello1, Carlos A Mandarim-de-Lacerda, Márcia B Aguila

  • 1Laboratory of Morphometry and Cardiovascular Morphology, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Av. 28 de Setembro 87 (fds), 20551-030 Rio de Janeiro, RJ, Brazil.

The British Journal of Nutrition
|June 15, 2007
PubMed

Insights

Perinatal protein restriction combined with a high-fat (HF) diet significantly impacts rat liver health, increasing steatosis and hypertension, especially in males. These findings underscore the critical roles of both fetal programming and postnatal nutrition in chronic disease development.

Area of Science:

  • Nutritional Science
  • Developmental Biology
  • Hepatic Pathology

Background:

  • Perinatal protein restriction can alter offspring development and disease susceptibility.
  • Post-weaning high-fat (HF) diets are known contributors to metabolic dysfunction.
  • Interactions between early-life nutrition and later diet are crucial for long-term health outcomes.

Purpose of the Study:

  • To investigate the combined effects of perinatal protein restriction and a post-weaning high-fat (HF) diet on hepatic morphology and metabolic parameters in rats.
  • To determine the influence of sex on these diet-induced changes.
  • To elucidate the long-term consequences of early-life nutritional insults.

Main Methods:

  • Wistar rats were fed normal-protein (NP) or low-protein (LP) diets during gestation.
  • Offspring were weaned onto standard chow or a high-fat (HF) diet.
  • Body mass, fat pad mass, liver mass:tibia length ratio, and hepatic histology (binucleation, hepatocyte area, steatosis) were assessed at 6 months.
  • Systolic blood pressure, insulin, and leptin levels were measured.
  • Statistical analyses included three-way and two-way ANOVA.

Main Results:

  • A significant three-way interaction (sex, perinatal diet, HF diet) affected body mass, fat pad mass, liver mass:tibia length ratio, binucleation rate, and hepatocyte area.
  • The HF diet exacerbated the effects of perinatal protein restriction on systolic blood pressure, genital fat pad, and hepatocyte number.
  • Males fed the HF diet exhibited higher steatosis rates, insulin, and leptin levels, indicating a sex-post-weaning diet interaction.
  • Combined fetal programming and HF diet led to mild hypertension, reduced hepatocyte number, and stage 1 steatosis, which worsened with continued HF diet exposure.

Conclusions:

  • Intra-uterine conditions and postnatal diet quality are critical determinants in the pathogenesis of chronic diseases.
  • The combination of perinatal protein restriction and a post-weaning high-fat diet significantly impairs hepatic morphology and metabolic health in a sex-dependent manner.
  • Early-life nutritional interventions are essential for mitigating long-term disease risk.

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