Parental dietary vitamin B12 and folate deficiency: defining epigenetic mechanisms underlying offspring cardio-metabolic health

父母膳食维生素 B12 和叶酸缺乏：定义后代心脏代谢健康的表观遗传机制

• 批准号: 2746121
• 金额: --
• 依托单位: Nottingham Trent University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2746121
• 关键词: Parental; dietary; vitamin; B12; folate

Background: Human epidemiological data and animal studies indicate that poor parental diet around the time of conception increases the risk for cardio-metabolic disease in offspring over multiple generations. These observations highlight epigenetic factors as one potential mechanism linking parental diet with the programmed ill-health of their offspring. Whilst post-conception consequences of general dietary imbalances of either parent in isolation has been established, there is little information on the interactive impact of both parental diets on offspring health, and no data on the effects of disturbances to one-carbon metabolism; which we have demonstrated is central to the epigenetic regulation of embryonic development and offspring wellbeing.Hypothesis: Dietary deficiencies in vitamin B12 and folate has been shown to disturb one-carbon metabolism in parents, leading to epigenetic modifications in offspring, thereby perturbing their development, health and well-being. We hypothesise that if both parents consume the same sub-optimal, low B12/folate diet (which is highly likely to occur in human couples), this will have a greater impact on offspring development and well-being than for either parent alone. Parentally inherited epigenetic modifications driving differential patterns of gene expression, tissue function and offspring growth will underlie these effects. Aims: In a factorially arranged design, we will define the parental-specific contribution to offspring health through feeding male and female mice either a low B12/folate diet or a control diet, for 7 weeks prior to mating, to ensure all stages of gamete development and maturation are exposed to the diets. Males and females will then be mated in combination to determine the specific impact of (i) paternal low one-carbon diet alone; (ii) maternal low one-carbon diet alone, (iii) combined parental low one-carbon diet or (iv) combined control parental diet. Approach: Throughout the feeding period, samples of maternal and paternal blood will be collected and assayed for metabolic endpoints of one-carbon metabolism (by LC-MS/MS (Antonysunil lab, NTU).

背景：人类流行病学数据和动物研究表明，受孕期间父母饮食不良会增加后代患心脏代谢疾病的风险。这些观察结果强调表观遗传因素是一种潜在机制，将父母的饮食与其后代的程序性不良健康联系起来。虽然父母任何一方单独饮食失衡的受孕后后果已经确定，但关于父母双方饮食对后代健康的相互作用影响的信息很少，也没有关于单碳代谢紊乱影响的数据；我们已经证明，这对于胚胎发育和后代健康的表观遗传调控至关重要。假设：维生素 B12 和叶酸的膳食缺乏已被证明会扰乱父母的一碳代谢，导致后代发生表观遗传修饰，从而扰乱他们的发育、健康和福祉。我们假设，如果父母双方都食用相同的次优、低维生素 B12/叶酸饮食（这在人类夫妇中极有可能发生），那么这对后代发育和福祉的影响将比单独父母一方更大。驱动基因表达、组织功能和后代生长差异模式的亲本表观遗传修饰将是这些影响的基础。目的：在因子排列设计中，我们将通过在交配前 7 周喂养雄性和雌性小鼠低维生素 B12/叶酸饮食或对照饮食来确定亲本对后代健康的特定贡献，以确保配子发育和成熟的所有阶段都接触到饮食。然后将雄性和雌性进行组合交配，以确定（i）仅父亲的低一碳饮食的具体影响； (ii) 母亲单独低一碳饮食，(iii) 联合父母低一碳饮食或 (iv) 联合对照父母饮食。方法：在整个喂养期间，将收集母体和父体血液样本并分析一碳代谢的代谢终点（通过 LC-MS/MS（Antonysunil 实验室，NTU））。