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（由申请人提供）：成人行为和新陈代谢的新生儿编程可能是美国肥胖患病率上升的一个中介因素。编程是一种发育可塑性，它利用生命早期的暴露来训练复杂的生物过程，以实现预期的最佳功能。结合现代生活方式创造了宽松的“致肥胖”环境，孕产妇在怀孕期间营养过剩和新生儿过度喂养会导致日后肥胖增加和代谢失衡。主要针对啮齿类动物的研究表明，母亲在怀孕和哺乳期间摄入高脂肪、高糖、高热量饮食 (HCD) 会导致恒河猴的行为和新陈代谢加快，从而促进后代肥胖。 ，母亲的身体成分和妊娠饮食会改变婴儿的生长和新陈代谢，为了更好地研究新生儿编程，恒河猴肥胖模型允许在典型的社会住房中而不是单独居住时测量卡路里摄入量。这项提案将研究在怀孕期间随意喂养 HCD 或低脂肪高纤维 (LCD) 的母亲所生的雌性恒河猴。怀孕和哺乳期间的 HCD 会比接触 LCD 的人消耗更多的食物，但由于能量消耗（体力活动、线性生长）的补偿性增加，过量的食物消耗对幼年后代的体重和体脂量的影响可能有限。 ，或性内脏和异位部位有害的脂肪堆积以胰岛素抵抗和慢性炎症为标志，在 DEXA 扫描检测到身体脂肪增加之前，这些炎症可能会变得异常。我们将评估饮食、体力活动、生长、成熟、胰岛素敏感性。以及在胎儿期和生命早期由母亲 HCD 或 LCD 编程的婴儿以及在 20 个月大时断奶至 LCD 的婴儿的炎症，我们发现，此时的 HCD 挑战将增强母亲在后代中编程的变化。 HCD 以及产前 HCD 暴露将延长 26 个月 LCD 恢复后的代谢恢复时间。要测量的结果包括食物摄入量（使用新型自动喂食器）、体力活动（加速度测量）、生长（形态测量和循环 IGF-1）。和身体成分 (DEXA)、骨骼（X 射线）和青春期成熟（体格检查、血清黄体酮），以及代谢失调脂肪组织的测量，包括胰岛素抵抗（HOMA-IR、葡萄糖钳）、循环瘦素和脂联素以及慢性炎症标志物（CRP、IL-6、TNF-¿一种新型食品分配器将首次允许每个受试者在其典型的社会住房中进行特定的实验饮食并持续监测其随意的热量摄入。探索体重对母亲、儿童甚至后代健康的影响。