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，在受孕期间，父母饮食不佳会增加多代后代心脏代谢疾病的风险。这些观察结果凸显了表观遗传因素是将父母饮食与他们后代的不良健康联系起来的一种潜在机制。尽管已经建立了两位父母的一般饮食失衡后的概念后后果，但关于父母饮食对后代健康的互动影响的信息很少，也没有关于扰动对单碳代谢的影响的数据。我们已经证明，这对于胚胎发育和后代健康的表观遗传调节至关重要。假设：维生素B12和叶酸中的饮食缺乏症已被证明会干扰父母的单碳代谢，从而导致后代的表观遗传修饰，从而使他们的发育和健康和健康和身体健康和健康。我们假设，如果父母双方都消耗相同的次优，低B12/叶酸饮食（这在人夫妇中很可能发生），那么这将对后代的发展和福祉产生更大的影响，而不是对任何一个父母。源自基因表达，组织功能和后代生长的差异模式的父遗传遗传修饰将是这些影响的基础。目的：在一种有因由布置的设计中，我们将通过喂养雄性和雌性小鼠在交配前7周来定义父母对后代健康的贡献，或者在交配前7周，以确保配子发育的所有阶段和成熟阶段都暴露于饮食中。然后，男性和女性将结合结合，以确定（i）单独的低碳饮食的特定影响； （ii）单独使用母性低一碳饮食，（iii）父母的低一碳饮食或（iv）组合控制父母饮食。方法：在整个喂养期间，将收集和分析母体和父亲血液的样品，以进行单碳代谢的代谢终点（通过LC-MS/MS（NTU AntonySunil Lab）。