High carbohydrate diet programs metabolic enzyme gene expression modification in F2 generation wistar rat males

Abstract

Diets high in carbohydrates (HCD) negatively impact transgenerational metabolic health and phenotype, factors directly influenced by gene expression. This study investigates the effects of HCD feeding on gene expression of key enzymes of important metabolic pathways in the Parent (F0), first (F1) and second (F2) filial generations. Each generation consisted of a control and HCD group of male and female counterparts in the F0 and F1 generations. Female rat cohorts (F0) fed a control or high-carbohydrate diet were mated at pro-oestrous period with males fed with similar diets at a ratio of 1:1 overnight. The offspring of the F1 generation exposed to the same diet were mated (1:1) to produce the F2 generation fed on a control diet. Male animals in each generation were analysed for metabolic changes, gene expression, and phenotypic outcomes. The results indicate that HCD caused significant increases (P < 0.05) in body weight in both the F1 and F2 generations, fasting blood glucose in the F2 generation, as well as serum insulin and HOMA-IR in the F1 and F2 generations. The F0 and F1 HCD-fed rats demonstrated a significant increase (P < 0.05) in the expression of genes involved in glycolysis and glycogen synthesis, along with a significant decrease (P < 0.05) in the expression of genes for gluconeogenic enzymes. Additionally, there was an increase (P < 0.05) in the expression of genes associated with fatty acid biosynthesis and a decrease (P < 0.05) in β-oxidation gene expression, a pattern similarly observed in control-fed F2 male rats. These findings suggest that a parental diet high in carbohydrates can induce modifications in the gene expression of metabolic rate-limiting enzymes in F2 offspring, regardless of their diet. However, this study did not assess the epigenetic modifications potentially responsible for the observed transgenerational effects. Future research could investigate epigenetic changes such as DNA methylation and histone modifications, and also assess these effects in female animals.