Maternal High Fat Diet and Melanocortin System in Offspring

母亲的高脂肪饮食和后代的黑皮质素系统

• 批准号: 7997693
• 负责人: KEVIN L GROVE
• 金额: $ 9.41万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-21 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7997693
• 关键词: 1 year old; Acetylation; Adolescent; Adult; Affect; Age; Animal Feed; Animals; Area; Back; Biochemical; Biological Assay; Body Weight; Brain; CRH gene; Cardiovascular Diseases; Child; Childhood; Chromatin Structure; Computer Systems Development; Consumption; Coupled; Desire for food; Development; Diabetes Mellitus; Diet; Disease; Eating; Energy Metabolism; Environment; Epigenetic Process; Exposure to; Fatty acid glycerol esters; Feedback; Female; Fetal Liver; Fetus; Food Intake Regulation; Foundations; Future; Gene Expression; Genes; Health; Histones; Homeostasis; Human; Hyperlipidemia; Hypothalamic structure; In Vitro; Infant; Insulin; Insulin Resistance; Insulin-Like Growth Factor Receptor; Intervention; Lateral; Lead; Leptin; Life; Link; Lipids; Liver; Liver diseases; Long-Term Effects; Maternal Health; Messenger RNA; Metabolic; Metabolic Diseases; Metabolism; Methylation; Modeling; Modification; Morbid Obesity; Mutation; Neonatal; Neurons; Neuropeptides; Newborn Infant; Nutrient; Obesity; Output; Overweight; Peptides; Peripheral; Phenotype; Predisposition; Pregnancy; Prevention; Primates; Proprotein Convertase 1; Proteins; Public Health; Receptor Signaling; Regulation; Research Personnel; Risk; Rodent; Sheep; Signal Transduction; Staging; Synapses; System; Therapeutic; Triglycerides; United States; Woman; base; critical period; design; detection of nutrient; diabetic; early onset; energy balance; feeding; fetal; good diet; hypocretin; in utero; in vivo; male; maternal diabetes; melanocortin receptor; neuron development; non-alcoholic fatty liver; nonhuman primate; offspring; postnatal; prenatal; prevent; programs; prohormone; receptor expression; response; syndecan; trend

DESCRIPTION (provided by applicant): The past several decades have revealed a devasting trend- the dramatic increase in preventable diseases in children, including obesity, diabetes, cardiovascular disease and nonalcoholic fatty liver disease (NAFLD). The general hypothesis of this proposal is that diet and metabolic health (such as obesity and diabetes) during pregnancy and the early neonatal period significantly contribute to the development of metabolic diseases in children, predisposing them to widespread health risks throughout life. We have developed a nonhuman primate (NHP) model of high fat/calorie diet-induced maternal obesity/diabetes in which to determine the immediate and long-term effects on body weight homeostasis in offspring. The specific focus of this proposal is the melanocortin neurons in the hypothalamus, which are critical for the homoeostatic feedback control of food intake and energy balance in response to peripheral adiposity signals. We predict that consumption of a high fat/calorie diet during pregnancy, resulting in maternal hyperlipidemia and insulin resistance, will cause an abnormal development of these neurons during in the fetal period, leading to a long-term reprogramming. We also predict that this phenotype will be exacerbated by exposure to the same diet during the postnatal period. With these developmental abnormalities, we expect the offspring to be predisposed to early onset obesity and ultimately diabetes These studies will use a variety of in vivo and in vitro physiolgical assays, combined with anatomical and biochemical assays to determine the effects of maternal high fat diet induced obesity/diabetes on the development of hypothalamic melanocortin system in the offspring during the late fetal and juvenile stages. Finally, we will investigate if feeding a healthy diet to obese/diabetic NHPs specifically during pregnancy can protect against the development of metabolic abnormalties in the offspring. With these studes, we hope to demonstrate that simply being overweight and eating a high fat diet causes metabolic disease in babies; a maternal phenotype that matches the majority of pregnancies in the United States. Furthermore, that eating a healthy diet specifically during pregnancy, even in obese/diabetic animals, can protect against the development of these diseases. This information will be critical for designing a viable prevention and has enormous public health implications

描述（由申请人提供）：过去几十年揭示了一个毁灭性的趋势-儿童可预防疾病的急剧增加，包括肥胖症，糖尿病，心血管疾病和非酒精性脂肪性肝病（NAFLD）。这一建议的一般假设是，怀孕期间和新生儿早期的饮食和代谢健康（如肥胖和糖尿病）大大有助于儿童代谢疾病的发展，使他们在一生中面临广泛的健康风险。我们已经开发了一个非人灵长类动物（NHP）模型的高脂肪/热量饮食诱导的母亲肥胖/糖尿病，以确定在后代的体重动态平衡的直接和长期影响。该建议的具体焦点是下丘脑中的黑皮质素神经元，其对于响应于外周肥胖信号的食物摄入和能量平衡的稳态反馈控制至关重要。我们预测，在怀孕期间食用高脂肪/热量饮食，导致母体高脂血症和胰岛素抵抗，将导致这些神经元在胎儿期的异常发育，导致长期重编程。我们还预测，这种表型将加剧暴露于相同的饮食在出生后期间。由于这些发育异常，我们预计后代易患早发性肥胖症并最终患糖尿病。这些研究将使用各种体内和体外生理学测定，结合解剖学和生物化学测定来确定母体高脂肪饮食诱导的肥胖/糖尿病对胎儿晚期和幼年期后代下丘脑黑皮质素系统发育的影响。最后，我们将调查是否喂养一个健康的饮食肥胖/糖尿病NHP特别是在怀孕期间可以防止代谢异常的后代的发展。通过这些研究，我们希望证明，仅仅是超重和吃高脂肪饮食就会导致婴儿代谢疾病;这是一种与美国大多数孕妇相匹配的母体表型。此外，特别是在怀孕期间，即使是肥胖/糖尿病动物，也可以预防这些疾病的发展。这些信息对于设计可行的预防措施至关重要，并具有巨大的公共卫生影响