Mechanisms Underlying the Association between Maternal and Offspring Obesity

母亲和后代肥胖之间关联的机制

• 批准号: 8468698
• 负责人: Paula Catherine Chandler-Laney
• 金额: $ 14.18万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8468698
• 关键词: Achievement; Adipose tissue; Adverse effects; Alabama; Basic Science; Behavior Therapy; Behavioral; Birth; C-Peptide; Child; Conduct Clinical Trials; Data; Deposition; Development Plans; Energy Intake; Energy Metabolism; Environment; Epidemiology; Faculty; Female of child bearing age; Fetus; Future; Glucose; Goals; Growth; Health; High Prevalence; Hyperinsulinism; Institution; Insulin; Intervention; Life; Link; Lipids; Literature; Measures; Mediating; Mentored Research Scientist Development Award; Mentors; Metabolic; Metabolism; Modeling; Monitor; National Institute of Diabetes and Digestive and Kidney Diseases; Neonatal; Neurosciences; Nonesterified Fatty Acids; Obesity; Outcome; Pathway interactions; Physiological; Placenta; Positioning Attribute; Postdoctoral Fellow; Pregnancy; Pregnant Women; Protocols documentation; Psychology; Public Health; Publishing; Recruitment Activity; Regulation; Relative (related person); Research; Research Personnel; Research Training; Resources; Risk; Satiation; Solid; Testing; Time; Training; Translating; Triglycerides; Umbilical Cord Blood; Umbilical cord structure; Universities; Weight; Weight Gain; Woman; adipokines; career; career development; design; early childhood; experience; fasting glucose; fetal; fetal programming; glucose metabolism; implementation research; indexing; infancy; insulin sensitivity; lipid metabolism; member; non-diabetic; novel; nutrition; obesity in children; obesity risk; offspring; post-doctoral training; prenatal; programs; prospective; screening; tool; training project; Achievement; Adipose tissue; Adverse effects; Alabama; Basic Science; Behavior Therapy; Behavioral; Birth; C-Peptide; Child; Conduct Clinical Trials; Data; Deposition; Development Plans; Energy Intake; Energy Metabolism; Environment; Epidemiology; Faculty; Female of child bearing age; Fetus; Future; Glucose; Goals; Growth; Health; High Prevalence; Hyperinsulinism; Institution; Insulin; Intervention; Life; Link; Lipids; Literature; Measures; Mediating; Mentored Research Scientist Development Award; Mentors; Metabolic; Metabolism; Modeling; Monitor; National Institute of Diabetes and Digestive and Kidney Diseases; Neonatal; Neurosciences; Nonesterified Fatty Acids; Obesity; Outcome; Pathway interactions; Physiological; Placenta; Positioning Attribute; Postdoctoral Fellow; Pregnancy; Pregnant Women; Protocols documentation; Psychology; Public Health; Publishing; Recruitment Activity; Regulation; Relative (related person); Research; Research Personnel; Research Training; Resources; Risk; Satiation; Solid; Testing; Time; Training; Translating; Triglycerides; Umbilical Cord Blood; Umbilical cord structure; Universities; Weight; Weight Gain; Woman; adipokines; career; career development; design; early childhood; experience; fasting glucose; fetal; fetal programming; glucose metabolism; implementation research; indexing; infancy; insulin sensitivity; lipid metabolism; member; non-diabetic; novel; nutrition; obesity in children; obesity risk; offspring; post-doctoral training; prenatal; programs; prospective; screening; tool; training project

DESCRIPTION (provided by applicant): I am a 4th year postdoctoral fellow preparing to transition to a junior faculty position. During my postdoctoral training, I have been actively engaged in research regarding prenatal programming of childhood obesity risk. I bring to this research a diverse training background in psychology, behavioral neuroscience, nutrition, and metabolism, as indicated by my publishing record. At this juncture, I seek an NIDDK-sponsored K01 award to support a project that will investigate mechanisms underlying prenatal programming, while concurrently providing me with the opportunity to obtain further training in physiological and behavioral predictors of childhood obesity. In addition, I will use this protected time to train in the design and conduct of clinical trials, particularly pertaining to behavioral interventions with longitudinal outcomes. These activities will ultimately help me to build a career in translating findings from basic research into feasible behavioral interventions to reduce the risk of obesity among offspring of obese women. The institution within which I will undertake my Career Development Plan is the University of Alabama at Birmingham (UAB). This highly successful institution maintains a supportive environment for training junior investigators, with many resources that facilitate both research and training. I have selected a team of two mentors with complementary expertise, one of whom is external to UAB but is a leader in the field of maternal obesity and prenatal programming. They have helped me to select three consultants who will oversee the implementation of research protocols, and a three-member career advisory panel that will monitor the progress of my career and the achievement of my short- and long-term goals. The revised project and training plan described in this application reflect the input of each member of this team. The proposed project will examine independent effects of maternal obesity and metabolic health on offspring risk for obesity. At least a portion of the risk for offspring obesity is believed to be attributable to excess fuel delivery to the developing fetus, which alters programming of fetal metabolism that ultimately may contribute to excess deposition of adipose tissue. Consequently, offspring of obese women are at greater risk because obesity-related metabolic abnormalities, such as reduced insulin sensitivity and abnormal substrate metabolism, increase the availability of fuel to the fetus. It is not known, however, whether maternal obesity in the absence of poor metabolic health will contribute to offspring risk for obesity. Similarly, normal weight women may be dichotomized into those of good or poor metabolic health. The overall goal of this study is to test the hypothesis that offspring of obese but metabolically healthy women have less risk for obesity as compared to offspring of metabolically unhealthy women. Using a two-way factorial design, women will be recruited to fill normal weight vs. obese, high vs. low fasting glucose groups. Glucose and lipid metabolism will be rigorously assessed to examine whether fasting glucose is a useful screening tool for poor metabolic health during pregnancy (Specific Aim 1). The independent effects of maternal obesity and metabolic health on neonatal adiposity and umbilical cord C-peptide will be assessed (Specific Aim 2). Finally, a hypothesized pathway linking maternal weight and substrate metabolism, to fetal insulin, and to subsequent weight gain at 0- 3 years will be tested (Specific Aim 3). The novelty of the proposed study lies in the examination of the independent effects of maternal obesity and metabolic health on mechanisms underlying the prenatal programming of childhood obesity risk. If, as hypothesized, maternal metabolic health has a greater influence on offspring risk than does maternal obesity, future intervention efforts can focus on maintaining optimal metabolic health during pregnancy, irrespective of weight status.

描述（由申请人提供）：我是准备过渡到初级教师职位的第四年。在博士后培训期间，我一直积极从事有关儿童肥胖风险产前编程的研究。我为这项研究带来了心理学，行为神经科学，营养和代谢的多样化培训背景，这是我的出版记录所表明的。在此关头，我寻求NIDDK赞助的K01奖，以支持一个项目，该项目将调查产前编程的机制，同时为我提供了获得儿童肥胖症生理和行为预测指标的进一步培训的机会。此外，我将使用这个受保护的时间来训练临床试验的设计和进行，尤其是与具有纵向结果的行为干预措施有关的。这些活动最终将帮助我建立从基础研究转化为可行的行为干预措施的职业，以减少肥胖妇女后代的肥胖风险。我将执行职业发展计划的机构是伯明翰（UAB）的阿拉巴马大学。这个非常成功的机构为培训初级调查人员提供支持环境，并提供许多促进研究和培训的资源。我选择了一个具有互补专业知识的两个导师的团队，其中一个是UAB的外部，但是孕产妇肥胖和产前节目领域的领导者。他们帮助我选择了三名将监督研究协议实施的顾问，以及由三人组成的职业咨询小组，这些小组将监控我的职业生涯的进步以及我短期和长期目标的实现。本申请中描述的修订项目和培训计划反映了该团队每个成员的输入。拟议的项目将研究孕产妇肥胖和代谢健康对肥胖后代风险的独立影响。据信，至少有一部分后代肥胖的风险归因于向发育中的胎儿过量输送过多的燃料，这改变了胎儿代谢的编程，最终可能导致脂肪组织的过量沉积。因此，肥胖妇女的后代面临更大的风险，因为与肥胖相关的代谢异常，例如胰岛素敏感性降低和异常底物代谢，增加了对胎儿燃料的可用性。但是，尚不知道在没有代谢健康不良的情况下产妇肥胖是否会导致肥胖的后代风险。同样，正常体重女性可能会被二分成良好或差的代谢健康。这项研究的总体目的是检验以下假设：与代谢性不健康的女性相比，肥胖但代谢健康的女性的后代患肥胖风险较小。使用双向阶乘设计，将招募妇女以填补正常体重与肥胖，而低的禁食葡萄糖组。葡萄糖和脂质代谢将进行严格评估，以检查空腹葡萄糖是否是怀孕期间代谢健康不良的有用筛查工具（特定目标1）。孕产妇肥胖和代谢健康对新生儿肥胖和脐带C肽的独立影响（特定目标2）。最后，将测试一种假设的途径，将孕妇体重和底物代谢，胎儿胰岛素以及随后在0-3年的随后体重增加联系起来（特定目标3）。拟议的研究的新颖性在于检查孕产妇肥胖和代谢健康对儿童肥胖风险产前编程的机制的独立影响。如假设的那样，孕产妇的代谢健康对后代风险的影响比产妇肥胖更大，未来的干预工作可以集中于在怀孕期间保持最佳代谢健康，而与体重状况无关。