Chimezie Joseph, Agbonifo Worship Odosa, Francis Hope Oluwabukola, Awoleye Mercy Oluwaseun, Adedeji Temitope Gabriel
Epigenetics and Molecular Biology Laboratory, Federal University of Technology, Akure, Nigeria.
Department of Physiology, School of Basic Medical Sciences, Federal University of Technology, Akure, Nigeria.
Curr Res Physiol. 2025 Jun 18;8:100154. doi: 10.1016/j.crphys.2025.100154. eCollection 2025.
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.
高碳水化合物饮食（HCD）对跨代代谢健康和表型产生负面影响，而这些因素直接受基因表达影响。本研究调查了HCD喂养对亲代（F0）、第一代（F1）和第二代（F2）子代重要代谢途径关键酶基因表达的影响。每一代均由F0和F1代中雄性和雌性对应的对照组和HCD组组成。在发情前期，将喂食对照或高碳水化合物饮食的雌性大鼠队列（F0）与喂食相似饮食的雄性大鼠按1:1比例过夜交配。将暴露于相同饮食的F1代后代按1:1比例交配，以产生喂食对照饮食的F2代。对每一代的雄性动物进行代谢变化、基因表达和表型结果分析。结果表明，HCD导致F1和F2代体重显著增加（P < 0.05），F2代空腹血糖升高，以及F1和F2代血清胰岛素和HOMA-IR升高。F0和F1代喂食HCD的大鼠在参与糖酵解和糖原合成的基因表达上显著增加（P < 0.05），同时糖异生酶基因表达显著降低（P < 0.05）。此外，与脂肪酸生物合成相关的基因表达增加（P < 0.05），β-氧化基因表达降低（P < 0.05），在喂食对照饮食的F2代雄性大鼠中也观察到类似模式。这些发现表明，亲代高碳水化合物饮食可诱导F2代后代代谢限速酶的基因表达发生改变，无论其饮食如何。然而，本研究未评估可能导致观察到的跨代效应的表观遗传修饰。未来的研究可以调查DNA甲基化和组蛋白修饰等表观遗传变化，并在雌性动物中评估这些效应。
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