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

母婴添加糖摄入量与婴儿脂肪组织增长的关系

• 批准号: 10518239
• 负责人: Holly Renee Hull
• 金额: $ 3.91万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10518239
• 关键词: 7 year old; Academy; Adipocytes; Adipose tissue; Age; Age-Months; Animal Experimentation; Birth; Body Composition; Body measure procedure; Cell Differentiation process; Characteristics; Child; Childhood; Clinical Trials; Data; Deposition; Development; Diet; Disease; Docosahexaenoic Acids; Docosahexaenoic acid supplementation; Dose; Double-Blind Method; Drug or chemical Tissue Distribution; Dual-Energy X-Ray Absorptiometry; Enrollment; Exposure to; Family; Fatty acid glycerol esters; Female; Fetal Development; Follow-Up Studies; Funding; Gender; Gene Expression; Generations; Genes; Goals; Growth; Human; Infant; Intake; Knowledge; Lead; Life; Life Expectancy; Link; Measures; Medical Care Costs; Medicine; Metabolic Diseases; Mothers; Nutrient; Obesity; Observational Study; Omega-3 Fatty Acids; Overweight; Parents; Phase; Phenotype; Placebo Control; Polyunsaturated Fatty Acids; Pregnancy; Pregnant Women; Premature Birth; Prevalence; Randomized; Recommendation; Regulation; Research Design; Severity of illness; Supplementation; Testing; Visceral; Weight Gain; Woman; adipocyte differentiation; base; cohort; critical period; disorder risk; effective intervention; efficacy testing; evidence based guidelines; experience; fatty acid metabolism; fetal; gestational weight gain; improved; innovation; lipid biosynthesis; neonate; obesity in children; obesity risk; offspring; offspring obesity; overweight child; oxidation; parent grant; prenatal; prenatal exposure; prevent; programs; response; sexual dimorphism; sugar; therapeutic target

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.

A) 资助的家长补助金摘要（R01DK118220） 儿童肥胖症的患病率急剧上升，因此预计儿童肥胖症的发病率将迅速上升 预期寿命的代际下降和后代承受过度医疗费用的激增。 妊娠期体重增加（GWG）在儿童时期具有更大的总脂肪量（FM）和中心性肥胖，并且 目前，56% 的孕妇体重增加过多。 对于经历 GWG 的怀孕，了解影响 FM 积累和直接影响的因素至关重要。 脂肪组织 (AT) 分布，因为它们是肥胖发生、疾病风险和肥胖发生的重要早期驱动因素 多不饱和脂肪酸 (PUFA) 影响脂肪细胞发育和 FM。 通过两种方式增加：影响细胞分化和增加产前脂肪酸代谢调节。 接触 n-3 脂肪酸家族，包括二十二碳六烯酸 (DHA)，可阻止脂肪细胞成熟 抑制参与脂肪生成的基因并增加参与β的基因的表达 总体净效应是 AT 沉积减少。 然而，母体 DHA 水平会降低后代 FM、内脏 AT 和较高的无脂肪体重。 缺乏来自随机对照试验的数据，该随机对照试验研究了当代美国队列中产前补充 DHA 的情况 这项研究将直接测量后代脂肪的增加和分布。 III 期随机、双盲和安慰剂对照美国妊娠队列（R01 HD083292， ClinicalTrials.gov ID：NCT02626299），其中 n=400 名女性将被随机分配到 1000 毫克/天或 200 毫克/天 怀孕期间 DHA 毫克/天。 后续研究的目的是确定产前剂量的 DHA 如何与 GWG 相互作用以达到 缺乏研究重要调节因素和潜在治疗方法的数据。 在前 1,000 个关键时期影响后代生长和身体成分变化的目标 这对后代表型的编程具有重要意义，为了制定有效的干预措施。 了解可以预防与代谢相关的后代表型的营养素非常重要 人类和基础动物研究的观察证据表明，DHA 是一种营养素。 在美国女性的饮食中普遍含量较低的物质可能就是这样一种营养素，这个项目是创新的，利用了一种营养物质。 针对美国孕妇补充高剂量和低剂量 DHA 的大型、持续的随机对照试验，测试其功效 对 GWG 过多的女性补充 DHA 的研究，并使用身体成分的直接测量 (DXA) 该数据将揭示有关高水平产前 DHA 影响的知识差距。 对后代 FM 应计计划的补充 该提案将有助于确定新的需求。 美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必需营养素）并制定了基于证据的 DHA 补充指南 怀孕期间目前不存在。