Maternal and Infant Added Sugars Intake in Relation to Infant Adipose Tissue Accrual

A)受资助父母补助金摘要(R01DK118220) 儿童肥胖症的流行率急剧上升，这导致了 预期寿命的代际下降和医疗费用的激增是造成这种现象的原因。暴露在过量环境中的后代 妊娠期体重增加(GWG)在儿童时期有更大的总脂肪质量(FM)和中心性肥胖，并且 更有可能超重或肥胖。目前，56%的孕妇GWG过高。在……里面 妊娠经历GWG，关键是要了解影响FM堆积和直接 脂肪组织(AT)分布，因为它们是肥胖发生、疾病风险和 疾病发展的严重性。多不饱和脂肪酸对脂肪细胞发育和FM的影响 通过两种方式产生作用：影响细胞分化和调节脂肪酸代谢。胎儿期增加 接触n-3脂肪酸家族，包括二十二碳六烯酸(DHA)，会阻止脂肪细胞成熟 抑制脂肪生成相关基因，增加β相关基因表达 氧化。总体的净影响是AT沉积的减少。观察性研究将更大的 儿童时期母体DHA水平与子代FM、内脏AT和较大的脱脂质量有关。然而， 从RCT研究当代美国队列中缺乏数据，在这些队列中，产前补充了DHA 并直接测量子代脂肪的积累和分布。这项研究将利用正在进行的 第三阶段随机、双盲、安慰剂对照的美国妊娠队列(R01 HD083292， ClinicalTrials.gov ID：NCT02626299)，其中n=400名女性将被随机分为1000 mg/天或200 mg/天 孕期服用DHA毫克/天。 随访研究的目的是确定产前剂量的DHA如何与GWG相互作用 影响后代调频计提。缺乏检查重要调节剂和潜在治疗方法的数据 在前1000人的关键时期影响后代生长和身体成分变化的目标 建议对后代的表型编程有重要意义的天数。为了制定有效的干预措施，它 对于理解营养物质对于防止与代谢有关的后代表型很重要。 疾病风险。在人类和基础动物研究中的观察证据表明，DHA，一种营养素 在美国女性的饮食中普遍偏低，可能是这样的一种营养物质。该项目具有创新性，充分利用了 美国孕妇大、持续、低剂量DHA补充剂的随机对照试验，测试其疗效 在GWG过多的女性中补充DHA，并使用直接测量身体成分的方法 (DXA)。这一数据将告知关于产前高水平DHA影响的知识差距 关于子孙调频应计项目的补充。该提案将有助于确定新的 我国国家医学科学院关于产前补充DHA的建议(DHA不是 在美国被认为是一种基本营养素)，并导致以证据为基础的DHA补充指南 在怀孕期间，目前还没有。

A) Abstract of the funded parent grant (R01DK118220) The prevalence of childhood obesity has dramatically increased leading to the prediction of a rapid generational decline in life expectancy and to a surge in medical care costs. Offspring exposed to excessive gestational weight gain (GWG) have greater total fat mass (FM) and central adiposity in childhood and are more likely to be overweight or obese. Currently, 56% of pregnant women experience excessive GWG. In pregnancies that experience GWG, it is critical to understand factors that influence FM accumulation and direct adipose tissue (AT) distribution as these are important early drivers of obesity occurrence, disease risk, and severity of disease development. Polyunsaturated fatty acids (PUFA) influence adipocyte development and FM accrual in two ways: influencing cell differentiation and fatty acid metabolism regulation. Increased prenatal exposure to the n-3 fatty acid family, including docosahexaenoic acid (DHA), prevented adipocyte maturation and suppressed genes involved in lipogenesis and increased the expression of genes involved with β oxidation. The overall net effect was a decrease in AT deposition. Observational studies associate greater maternal DHA levels with lower offspring FM, visceral AT and greater fat-free mass in childhood. However, data are lacking from RCT studying a contemporary U.S. based cohort where DHA is prenatally supplemented and offspring fat accrual and distribution are directly measured. This study will take advantage of an ongoing Phase III randomized, double blinded, and placebo controlled U.S. based pregnancy cohort (R01 HD083292, ClinicalTrials.gov ID: NCT02626299) in which n=400 women will be randomized to either 1000 mg/day or 200 mg/day of DHA during pregnancy. The purpose of the follow-up study is to determine how the prenatal dose of DHA interacts with GWG to influence offspring FM accrual. Data are lacking that examine important moderators and potential therapeutic targets that influence offspring growth and body composition changes during a critical period of the first 1,000 days suggested to be significant for programming the offspring phenotype. To develop effective interventions, it is important to understand nutrients that may protect against an offspring phenotype related to metabolic disease risk. Observational evidence in humans and basic animal research suggest that DHA, a nutrient generally low in the diet of US women, could be such a nutrient. This project is innovative, capitalizing on a large, ongoing, RCT of high and low-dose DHA supplementation of U.S. pregnant women, testing the efficacy of DHA supplementation in women with excessive GWG, and using direct measures of body composition (DXA). This data will inform the gap in knowledge regarding the impact of high levels of prenatal DHA supplementation on programming offspring FM accrual. The proposal will help identify the need for new recommendations for prenatal DHA supplementation by our National Academy of Medicine (DHA is not recognized in the US as an essential nutrient) and lead to evidence-based guidelines for DHA supplementation during pregnancy where none currently exist.