PD552 - TRANSGENERATIONAL EFFECTS OF INTRAUTERINE MALNUTRITION ON GLUCOSE HOMEOSTASIS AND TRIGLYCERIDE METABOLISM IN RATS: EVIDENCE FOR SEX-DEPENDENT METABOLIC PROGRAMMING.

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PD552

TRANSGENERATIONAL EFFECTS OF INTRAUTERINE MALNUTRITION ON GLUCOSE HOMEOSTASIS AND TRIGLYCERIDE METABOLISM IN RATS: EVIDENCE FOR SEX-DEPENDENT METABOLIC PROGRAMMING.

R. R. Ferreira1, S. Andreotti2, M. E. B. Padua3, L. R. Giaquinto1,4, M. A. Landgraf4, R. G. Landgraf3,*

1Medicine, Universidade Federal de São Paulo, 2Physiology, Universidade de São Paulo, São Paulo, 3Pharmaceutical Sciences, Universidade Federal de São Paulo, Diadema, 4Universidade Paulista, Santos, Brazil

 

Rationale: Maternal nutrient restriction during gestation programs persistent metabolic adaptations in offspring with potential transgenerational effects. Although such adaptations may confer short-term advantages, they are associated with an increased risk of metabolic disorders in adulthood. However, their long-term impact and sex-specific patterns remain incompletely understood.

Methods: Pregnant Wistar rats underwent 50% caloric and protein restriction during gestation. F2 offspring, generated from intercrossed F1 animals exposed to intrauterine growth restriction, were not subjected to dietary restriction and were grouped by parental lineage (P-F2, M-F2). At 12 weeks, animals were euthanized, and circulating pro- and anti-inflammatory cytokines, glucose, and triglycerides were quantified in both generations. Analyses were sex-stratified to assess sexually dimorphic metabolic responses. (CEUA UNIFESP nº 3888090925)

Results: F1 offspring exposed to intrauterine malnutrition exhibited marked hyperglycemia and hypertriglyceridemia relative to adequately nourished controls, consistent with early metabolic dysregulation. In F2 progeny, these metabolic alterations persisted despite the absence of direct nutritional insult. These effects were more pronounced in males, whereas females exhibited partial metabolic resilience. Circulating levels of IL-1β and IL-6 were comparable between generations in both sexes, whereas elevated IL-10 levels were observed exclusively in the F1 generation.

Conclusion: Intrauterine malnutrition induces persistent, sex-dependent metabolic dysfunction that extends into the second generation, underscoring the contribution of epigenetic mechanisms and developmental programming to cardiometabolic risk.

Disclosure of Interest: None declared