Neonatal Programming of Growth and Maturation in Rhesus Monkeys

恒河猴生长和成熟的新生儿编程

• 批准号: 8430236
• 负责人: Andrew B Muir
• 金额: $ 26.78万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-15 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8430236
• 关键词: Abdomen; Adipose tissue; Adult; Affect; Age; Age-Months; Animal Model; Area; Behavior; Behavioral; Biochemical Markers; Biological Process; Birth Weight; Blood specimen; Body Composition; Body fat; Bone Growth; C-reactive protein; Central obesity; Child; Chronic; Chronic Disease; Complex; Computers; DEXA; Daughter; Development; Diet; Dietary Fats; Disease; Diversion Program; Eating; Energy Intake; Energy Metabolism; Environment; Epidemiology; Epigenetic Process; Euglycemic Clamping; Experimental Animal Model; Fasting; Fatty acid glycerol esters; Feeds; Female; Fiber; Food; Funding; Future; Generations; Genetic; Glucose Clamp; Goals; Growth; Growth and Development function; Health; High Fiber Diet Low Fat; Housing; Human; Hypertriglyceridemia; Implant; Individual; Infant; Inflammation; Inflammatory; Ingestion; Insulin Resistance; Insulin-Like Growth Factor I; Intake; Interleukin-6; LDL Cholesterol Lipoproteins; Lactation; Learning; Length; Leptin; Life; Life Style; Link; Macaca mulatta; Measurement; Measures; Mediating; Mediator of activation protein; Metabolic; Metabolism; Methods; Modeling; Monitor; Monkeys; Mothers; Neonatal; Obesity; Outcome; Overnutrition; Ovulation; Physical Examination; Physical activity; Physiological; Predisposition; Pregnancy; Prevalence; Progesterone; Puberty; Publishing; Recovery; Recreation; Regulation; Research; Research Design; Resources; Risk; Rodent; Roentgen Rays; Scanning; Serum; Sexual Maturation; Shapes; Site; Study Subject; System; TNF gene; Therapy Clinical Trials; Time; Training; Translations; Tumor Necrosis Factor-alpha; Visceral; Weaning; Weight; Wrist; adiponectin; bone age; cohort; control trial; design; developmental plasticity; energy balance; feeding; fetal; fetus nutrition; food consumption; gene environment interaction; imprint; improved; insight; insulin sensitivity; mother nutrition; nonhuman primate; novel; obesogenic; offspring; postnatal; pregnant; prenatal; prepuberty; prevent; programs; promoter; public health relevance; radiofrequency; response; sedentary; skeletal; social; sugar; translational study

DESCRIPTION (provided by applicant): Neonatal programming of adult behavior and metabolism may be a mediator of the rising prevalence of obesity in the US. Programming is a developmental plasticity that uses exposures in early life to train complex biological processes towards optimal function in the anticipated future environment. Combined with modern lifestyles that have created a permissive "obesigenic" environment, maternal overnutrition during pregnancy and neonatal overfeeding are hypothesized to result in programming towards increased adiposity later in life and metabolic imbalances and inflammation that exacerbate obesity and its complications. Studies, mainly in rodents show that maternal ingestion of a high fat, high sugar, high calorie diet (HCD) during pregnancy and lactation programs behaviors and metabolism that promote obesity in the offspring. In rhesus monkeys, maternal body composition and gestational diet alter the growth and metabolism of the infants. To better study neonatal programming, a rhesus monkey model of obesity that allows measures of caloric intake while subjects live in their typical social housing, rather than in solitary cages has been developed. This proposal will study female rhesus monkeys born to mothers that were ad lib fed either a HCD or one that was low in fat and high in fiber (LCD) during pregnancy. We predict that throughout the study, infants exposed to a HCD during pregnancy and lactation will consume more food than those exposed to a LCD. Excess food consumption however may have a limited effect on the weight and body fat mass of young progeny, owing to compensatory increases in energy expenditure (physical activity, linear growth, or sexual maturation). Harmful accumulation of fat at visceral and ectopic sites is marked by insulin resistance and chronic inflammation that can become abnormal before body fat increases can be detected by DEXA scans. We will evaluate eating, physical activity, growth, maturation, insulin sensitivity, and inflammation in infants programmed by maternal HCD or LCD in fetal and early life and who were weaned to a LCD until age 20 months. We hypothesize that a HCD challenge at that point will augment changes programmed in the offspring by the maternal HCD and that prenatal HCD exposure will prolong the metabolic recovery after LCD is restored at 26 months. Outcomes to be measured include food intake (using a novel automated feeder), physical activity (accelerometry), growth (morphometric measurements and circulating IGF-1) and body composition (DEXA), skeletal (X-ray) and pubertal maturation (physical examination, serum progesterone), and measures of metabolically dysregulated adipose tissue, including insulin resistance (HOMA-IR, glucose clamp), circulating leptin and adiponectin, and markers of chronic inflammation (CRP, IL-6, TNF-¿). A novel food dispenser will for the first time allow specific access for each subject to experimental diets and continuous monitoring of their ad lib caloric intake while they remain in their typical social housing. A nonhuman primate model of gestational overnutrition is a vital resource to explore the effects of weight on the health of mothers, children, and perhaps even subsequent generations.

描述（由适用提供）：成人行为和代谢的新生儿编程可能是美国肥胖症患病率上升的中介。编程是一种发展性可塑性，它在早期生活中使用暴露量来训练复杂的生物学过程，以在预期的未来环境中培训最佳功能。假设，结合创造了允许的“超生族”环境的现代生活方式，怀孕期间的孕产妇营养不良和新生儿过度喂养的养育可以导致编程，以提高生命后来的肥胖，并使肥胖症及其复杂性加剧。研究主要是在啮齿动物中表明，在怀孕和哺乳计划行为和代谢中，高脂肪，高糖，高卡路里饮食（HCD）的物质摄入，从而促进后代的肥胖症。在恒河猴中，母体的体内成分和妊娠饮食改变了婴儿的生长和代谢。为了更好地研究新生儿编程，肥胖的恒河猴模型允许在受试者生活在典型的社会住房中，而不是在固体笼子中的受试者时进行热量摄入量。该提议将研究母亲所生的雌性恒河猴，这些猴子被送给了HCD或脂肪低且纤维含量高的雌性猴子。我们预测，在整个研究中，与暴露于LCD的婴儿相比，怀孕期间暴露于HCD的婴儿会消耗更多的食物。但是，由于能源消耗的补偿性增加（体育活动，线性生长或性成熟），过量食物消耗可能对年轻进度的体重和体内脂肪质量的影响有限。脂肪在内脏和异位部位的有害积累以胰岛素抵抗和慢性感染为标志，在DEXA扫描可以检测到体内脂肪增加之前可能会变得异常。我们将评估由Mater HCD或LCD在胎儿和早期生命中编程的婴儿中的饮食，体育锻炼，成长，胰岛素敏感性以及感染，并且他们断奶至LCD直至20个月大。我们假设当时的HCD挑战将增加Mater HCD在后代中编程的变化，并且产前HCD暴露将延长LCD在26个月时恢复后代谢回收率。 Outcomes to be measured include food intake (using a novel automated feeder), physical activity (accelerometry), growth (morphometric measurements and circulating IGF-1) and body composition (DEXA), skeletal (X-ray) and pubertal maturation (physical examination, serum progesterone), and measures of metabolically dysregulated adipose tissue, including insulin resistance (HOMA-IR,葡萄糖夹），循环瘦素和脂联素以及慢性炎症的标志物（CRP，IL-6，TNF-¿）。新颖的食物分配器将首次允许每个主题的特定访问实验饮食，并在其典型的社交住房中持续监测其AD Lib热量摄入量。妊娠营养营养的非人类私人模型是探索体重对母亲，儿童甚至可能后代健康的影响的重要资源。