Early Environmental Contributions to Adult Onset Obesity

早期环境对成人肥胖的影响

• 批准号: 7226004
• 负责人: Carrie de Evsikova
• 金额: $ 16.31万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7226004
• 关键词: Adult; Affect; Alcohols; American; Angelman Syndrome; Animals; Assisted Reproductive Technology; Back; Barker Hypothesis; Beckwith-Wiedemann Syndrome; Behavior; Birth Weight; Body Composition; Cell Nucleus; Child; Clinical; Cloning; Conceptus; Control Animal; Culture Media; DNA Methylation; Development; Disease; Embryo; Energy Metabolism; Environment; Ethanol; Female; Fertilization in Vitro; Gene Expression; Genome; Genome Components; Genomics; Genotype; Goals; Health Care Costs; Heart Diseases; Hereditary Disease; High Blood Pressure; Hormones; Human; In Vitro; Incidence; Individual; Intracytoplasmic Sperm Injections; Investigation; Knowledge; Laboratories; Lead; Life; Metabolic; Metabolic Diseases; Metabolic syndrome; Metabolism; Molecular; Monitor; Mus; Non-Insulin-Dependent Diabetes Mellitus; Numbers; Obesity; Oocytes; Organism; Outcome; Pathway interactions; Patient currently pregnant; Pattern; Persons; Phenotype; Physiological; Physiological Processes; Physiology; Predisposition; Procedures; Regulation; Research; Societies; Staging; System; Techniques; Test-Tube Baby; Testing; Therapeutic Intervention; United States; Weight Gain; Work; age related; alcohol exposure; cost; deviant; embryo culture; energy balance; fetal; imprint; in utero; innovation; mature animal; oocyte maturation; research study

DESCRIPTION (provided by applicant): Metabolic diseases, such as obesity and type II diabetes, are symptomatic illnesses of modern American society and obesity alone currently accrues $96 billion of direct health costs per year. Within 5 years, a third of adults in the US will be obese. While genotypes clearly contribute to the predisposition for obesity, it is the environment that determines its manifestation. Fetal environment is a critical factor for common adult diseases in humans, such as heart disease, high blood pressure, type II diabetes, and obesity. Animals produced through the use of assisted reproductive technology are susceptible to obesity in adulthood. Over a million people, since 1995, have been conceived using some form of assisted reproductive technology. Although few of these people have reached adulthood presently, most show signs of clinical obesity. The in vitro culture environment is known to alter the energy metabolism of oocytes and embryos in animals, as well as humans. The long-term goal of this proposed study is to determine how the in vitro culture environment affects homeostatic systems that lead to adulthood obesity. Most studies to date of metabolic disease alter the environment of the pregnant adult female. This study is innovative in that the early developmental environment will be controlled by using in vitro maturation and in vitro fertilization techniques; thereby allowing investigation of environmental influence on the early embryo, and the subsequent effects on the resulting adult animal. Although the constituents in culture media leading to obesity are not known, alcohol is one common component used in many assisted reproductive technology procedures. Results from our laboratory suggest that mice specifically exposed to ethyl alcohol during in vitro maturation of oocytes gradually become obese in adulthood. To pinpoint which physiological systems are involved in this adult-onset obesity, a comprehensive cage metabolic monitoring system, as well as changes in gene expression will be used to identify the alternations in energy regulation of mice exposed to alcohol as compared to controls. These experiments will help to elucidate the systems and pathways which are established within the early maternal and embryonic environment that influence a predisposition to adulthood diseases, such as obesity and type II diabetes.

描述（由申请人提供）：肥胖和 II 型糖尿病等代谢性疾病是现代美国社会的症状性疾病，目前仅肥胖一项就造成每年 960 亿美元的直接健康成本。五年之内，美国三分之一的成年人将肥胖。虽然基因型显然会导致肥胖倾向，但决定其表现的是环境。胎儿环境是人类常见成人疾病的关键因素，如心脏病、高血压、II型糖尿病和肥胖症。使用辅助生殖技术生产的动物在成年后容易患肥胖症。自 1995 年以来，已有超过一百万人使用某种形式的辅助生殖技术受孕。尽管这些人中目前只有少数已成年，但大多数都表现出临床肥胖的迹象。众所周知，体外培养环境会改变动物以及人类卵母细胞和胚胎的能量代谢。这项拟议研究的长期目标是确定体外培养环境如何影响导致成年肥胖的稳态系统。迄今为止，大多数代谢疾病研究都会改变怀孕成年女性的环境。本研究的创新之处在于采用体外成熟和体外受精技术来控制早期发育环境；从而可以研究环境对早期胚胎的影响，以及随后对成年动物的影响。尽管培养基中导致肥胖的成分尚不清楚，但酒精是许多辅助生殖技术程序中使用的一种常见成分。我们实验室的结果表明，在卵母细胞体外成熟过程中专门暴露于乙醇的小鼠在成年后逐渐变得肥胖。为了查明哪些生理系统与这种成年发病的肥胖有关，将使用全面的笼代谢监测系统以及基因表达的变化来确定暴露于酒精的小鼠与对照组相比能量调节的变化。这些实验将有助于阐明在早期母体和胚胎环境中建立的影响成年期疾病（如肥胖和 II 型糖尿病）易感性的系统和途径。