The Common Marmoset as a Primate Model of Maternal Obesity

普通狨猴作为孕产妇肥胖的灵长类动物模型

• 批准号: 7289738
• 负责人: Michael L. Power
• 金额: $ 24.49万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-15 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7289738
• 关键词: Abdomen; Adult; Adult Children; Affect; Age-Months; Behavior; Behavioral; Birth; Birth Weight; Body Composition; CRH gene; Caliber; Callithrix jacchus jacchus; Cephalic; Corticotropin-Releasing Hormone; Cues; Development; Diet; Disease; Disease Outcome; Eating; Endocrine; Environment; Estradiol; Exposure to; Fat-Restricted Diet; Fatty acid glycerol esters; Feeding behaviors; Female; Fertility; Fetal Macrosomia; Food; Food Intake Regulation; Glucose; Glycosylated hemoglobin A; Goals; Growth; Growth and Development function; Homeostasis; Hyperinsulinism; Infant; Insulin; Length; Leptin; Life; Longevity; Metabolic; Metabolism; Modeling; Monkeys; OGTT; Obesity; Patient currently pregnant; Phase; Physiological; Population; Population Study; Pregnancy; Primates; Production; Regulation; Relative (related person); Research; Resistance; Response Latencies; Somatomedins; Source; Weaning; Weight; blood glucose regulation; diabetic; feeding; fetal; glucose metabolism; infancy; nonhuman primate; preference; response; size

DESCRIPTION (provided by applicant): Given their small size, high fertility and short life span, common marmosets are an efficient nonhuman primate model in which to examine the effects of early life environment on adult disease outcomes. The primary goal of the proposed research is to determine the extent to which maternal propensity to obesity or actual obesity predisposes offspring to disorders of glucose regulation and weight homeostasis in this species. These goals will be achieved through the following specific aims: 1. To establish and characterize four study populations of pregnant females that a. are made obese prior to pregnancy through exposures to a proven obesity-inducing, high-fat diet; b. have a propensity to DIO, but are maintained on the typical low fat diet during pregnancy; c. are spontaneously obese; or d. remain lean while exposed to a high fat diet. These four populations will be characterized relative to glucose metabolism and regulation, including baseline insulin and HbA1C, glucose, and response to an oral glucose tolerance test; food intake and physiological and behavioral responses to food; and body composition and circulating concentrations of leptin. 2. To characterize these study populations relative to the following variables during pregnancy and at birth: maternal glucose metabolism and regulation; maternal body composition and circulating concentrations of CRH, leptin and estradiol; placental and fetal growth and development, including placental function assessed through stereology and estimates of placental CRH, leptin and IGF production; endocrine markers of placental size and function; and infant birth weight and and circulating insulin concentration. 3. To characterize changes in body composition, feeding and metabolism from post-weaning infancy (6 months) to adulthood (24 months of age) in offspring of these pregnancies by: tracking growth trajectories while fed control or obesity-inducing diets; tracking development of feeding behaviors in weanling infants; determining response to food cues in adults; and tracking glucose metabolism and regulation. The primary null predictions are that obese females, regardless of the source of obesity will display a "pre-diabetic/mild diabetic" profile resulting in fetal macrosomia and hyperinsulinemia, that the DIO propensity group may differ from the diet resistant, lean group in terms of metabolic parameters; and that adult offspring will mirror their dam in terms of body composition, feeding behavior, and glucose metabolism.

描述（由申请人提供）：鉴于普通狨猴体型小、生育力高和寿命短，它们是一种有效的非人类灵长类动物模型，可用于检查早期生活环境对成年疾病结果的影响。拟议研究的主要目标是确定母亲的肥胖倾向或实际肥胖在多大程度上使该物种的后代容易出现葡萄糖调节和体重稳态紊乱。这些目标将通过以下具体目标来实现： 1. 建立并描述四个怀孕女性研究群体的特征：在怀孕前因接触经证实可诱发肥胖的高脂肪饮食而变得肥胖； b.有 DIO 倾向，但在怀孕期间维持典型的低脂饮食； c.自发性肥胖；或 d。在接受高脂肪饮食的同时保持苗条。这四个人群的特征在于葡萄糖代谢和调节，包括基线胰岛素和 HbA1C、葡萄糖以及对口服葡萄糖耐量试验的反应；食物摄入量以及对食物的生理和行为反应；以及身体成分和瘦素的循环浓度。 2. 描述这些研究人群在怀孕和出生期间相对于以下变量的特征：母亲葡萄糖代谢和调节；母体身体成分和 CRH、瘦素和雌二醇的循环浓度；胎盘和胎儿的生长和发育，包括通过体视学评估胎盘功能以及胎盘 CRH、瘦素和 IGF 产生的估计；胎盘大小和功能的内分泌标志物；和婴儿出生体重和循环胰岛素浓度。 3. 通过以下方式描述这些妊娠后代从断奶后婴儿期（6 个月）到成年期（24 个月大）身体成分、喂养和新陈代谢的变化： 跟踪喂养对照饮食或诱导肥胖饮食时的生长轨迹；跟踪断奶婴儿喂养行为的发展；确定成人对食物线索的反应；并跟踪葡萄糖代谢和调节。主要的无效预测是，肥胖女性，无论肥胖的来源如何，都会表现出“糖尿病前期/轻度糖尿病”特征，导致巨大胎儿和高胰岛素血症，DIO 倾向组可能与饮食抗拒的瘦组在这方面有所不同。代谢参数；成年后代将在身体成分、进食行为和葡萄糖代谢方面模仿其母亲。