The impact of gastric bypass on maternal and offspring metabolic health

胃绕道手术对母婴代谢健康的影响

• 批准号: 10355478
• 负责人: Paul Kievit
• 金额: $ 72.82万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-07 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10355478
• 关键词: 1 year old; Address; Affect; Age; Age-Months; Animals; Attenuated; Blood flow; Body Composition; Body Weight decreased; Body mass index; Caloric Restriction; Calories; Child; Clinical; Clinical Research; Conflict (Psychology); Consumption; Data; Development; Diet; Disease; Endocrine; Exposure to; Fatty acid glycerol esters; Female; Fetal Development; Fetal Growth; Fetal Growth Retardation; Fetal Malnutrition; Foundations; Frequencies; Future; Gastric Bypass; Germ-Free; Glucose; Growth; Health; Hormones; Human; Human Milk; Insulin Resistance; Intervention; Investigation; Laboratories; Lactation; Macaca mulatta; Malnutrition; Matched Group; Maternal Health; Measurement; Metabolic; Modeling; Monitor; Morbid Obesity; Morphology; Mothers; Mus; Obesity; Operative Surgical Procedures; Organ; Outcome; Pancreas; Patients; Physiological; Physiology; Positioning Attribute; Pregnancy; Pregnancy Complications; Program Development; Proteins; Research; Research Proposals; Risk; Risk Factors; Serum; Small for Gestational Age Infant; Testing; Treatment Efficacy; Weight; Woman; Work; attenuation; bariatric surgery; blood glucose regulation; comorbidity; fetal; fetus nutrition; gut microbiome; improved; improved outcome; in utero; insulin secretion; insulin sensitivity; maternal microbiome; maternal obesity; microbiome; microbiome alteration; microbiome composition; mother nutrition; nonhuman primate; novel; nutrient absorption; obese mothers; obesity development; obesity in children; obesity treatment; offspring; postnatal; pregnancy health; reproductive; sham surgery; transmission process; ultrasound; weight loss intervention; western diet

PROJECT SUMMARY Childhood obesity rates are at their highest recorded level of 17%, and an important emerging risk factor is maternal obesity. It is hypothesized that maternal obesity during critical stages of in utero development programs the risk for the development of obesity in the offspring, but the mechanism for this transmission remains unclear. One of the most efficient and long-lasting therapies for obesity in reproductive-age women is Roux-en-Y gastric bypass (RYGB) surgery, and recent results suggest that maternal RYGB may protect offspring from the development of obesity. However, conflicting data also indicates maternal RYGB may result in fetal malnutrition, which could have a lasting detrimental impact on offspring health. In the current proposal, we will utilize our long-standing nonhuman primate model of maternal western-style diet (WSD) consumption in conjunction with our newly developed model of nonhuman primate RYGB to determine how RYGB impacts both maternal health and offspring development. Previous work from our laboratory has found that fetal nonhuman primates exposed to a WSD in utero have a number of physiological changes, including alterations in postnatal growth curves and insulin sensitivity along with alterations in the pancreas. These findings will be the foundation to explore what, if any, beneficial impact maternal RYGB has to reverse these in utero WSD- induced alterations in offspring physiology. One novel mechanism by which maternal RYGB may impact offspring metabolic health is the microbiome. Our previous work has demonstrated that maternal diet and microbiome composition may have a long-term influence on the offspring microbiome. RYGB causes drastic changes to the patient's microbiome, which appear to promote weight-loss when transferred into germ-free mice. To our knowledge, no previous study has investigated how maternal RYGB may impact offspring microbiome and whether this alters metabolic physiology. The current research proposal hopes to address how RYGB impact both maternal metabolic health during pregnancy as well as offspring fetal growth and postnatal metabolic health with three specific aims: Specific Aim 1. Characterize the effect of RYGB on maternal metabolic health during pregnancy. Specific Aim 2. Determine the impact of maternal RYGB on offspring fetal growth and early postnatal metabolic health. Specific Aim 3. Assess the impact of RYGB on maternal and offspring microbiome.

项目摘要 儿童肥胖率达到17%的最高记录水平，这是一个重要的新兴风险。 一个重要因素是母亲肥胖。据推测，在子宫内发育的关键阶段， 计划在后代中发展肥胖症的风险，但这种传播的机制 仍不清楚对育龄妇女肥胖最有效和最持久的治疗方法之一是 Roux-en-Y胃旁路术（RYGB），最近的结果表明，母亲RYGB可能保护 肥胖症的后代。然而，相互矛盾的数据也表明，母亲RYGB可能导致 胎儿营养不良，这可能对后代的健康产生持久的有害影响。在目前的提案中， 我们将利用我们长期以来的非人类灵长类动物母体西式饮食（WSD）消费模型， 结合我们新开发的非人灵长类RYGB模型，以确定RYGB如何影响 孕产妇健康和后代发育。我们实验室以前的工作发现， 在子宫内暴露于WSD的非人灵长类动物有许多生理变化，包括改变 出生后的生长曲线和胰岛素敏感性沿着在胰腺的变化。这些发现将是 该基金会探索什么，如果有的话，有益的影响，产妇RYGB有扭转这些在子宫内WSD- 诱导后代生理学的改变。母体RYGB可能影响的一种新机制 后代的代谢健康是微生物组。我们以前的工作表明，母亲的饮食和 微生物组组成可能对后代微生物组产生长期影响。RYGB导致剧烈的 改变患者的微生物组，当转移到无菌环境中时， 小鼠据我们所知，以前没有研究调查母亲RYGB如何影响后代 微生物组以及这是否会改变代谢生理学。目前的研究计划希望解决如何 RYGB影响妊娠期母体代谢健康以及后代胎儿生长和出生后 代谢健康有三个具体目标： 具体目标1.描述RYGB对妊娠期间母体代谢健康的影响。 具体目标2。确定母体RYGB对后代胎儿生长和出生后早期的影响 代谢健康 具体目标3。评估RYGB对母体和后代微生物组的影响。