Influences of the prenatal environment on metabolic programming

产前环境对代谢程序的影响

• 批准号: 8052835
• 负责人: KELLIE L. K. TAMASHIRO
• 金额: $ 24.4万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-10-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8052835
• 关键词: Adolescence; Adult; Animal Model; Behavioral; Cardiovascular Diseases; Characteristics; Clinical; Consumption; DNA Methylation; DNA Methylation Regulation; Data; Development; Diabetes Mellitus; Diet; Disease; Endocrine; Environment; Epidemiology; Epigenetic Process; Etiology; Exposure to; Fatty acid glycerol esters; Funding; Genes; Goals; Health; Homeostasis; Human; Hypertension; Insulin Resistance; Intervention; Lactation; Lead; Life Style; Metabolic; Metabolic Diseases; Modification; Neuropeptides; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Personal Satisfaction; Phenotype; Physiological; Play; Prenatal Nutrition; Prevention strategy; Public Health; Rattus; Risk; Rodent Model; Role; Stress; System; Testing; Time; Work; effective therapy; neuropsychiatry; nutrition; offspring; prenatal; prenatal influence; prenatal stress; programs; research study; response

Obesity Is a major public health problem worldwide and recent work has suggested that exposure to a suboptimal eariy environment may increase the risk of becoming obese. Epidemiological data show that an unfavorable intrauterine environment has long-term consequences in offspring including hypertension, cardiovascular disease, type 2 diabetes, obesity and neuropsychiatric disease. Specifically, prenatal stress and/or consumption of a high fat dieL characteristics of modern day human lifestyle, have been shown to lead to metabolic disorders such as obesity and Insulin resistance in offspring. However, the mechanisms involved are not well understood. The overall goal of this proposal is to characterize the short- and long-tenn effects of changes in the prenatal environment - stress and nutrition - on the behavioral and physiological development of offspring and to explore the possible neuropeptide and epigenetic mechanisms involved using a rat animal model. Specific aims are: 1) To detemiine the developmental time course of behavioral and endocrine alterations resulting from prenatal stress. We will also test the hypothesis that prenatal stress will accentuate diet-induced obesity, Timepoints during lactation, adolescence, and adulthood will be examined to characterize the phenotype and to direct examination of possible mechanisms; 2) To test the hypothesis that prenatal stress, high fat diet, or both result in alterations in neuropeptide systems regulating energy homeostasis that are consistent with other rodent models of obesity; and 3) To test the hypothesis that prenatal stress and nutrition results in obesity in offspring through epigenetic modifications via differential DNA methylation of genes that are critical to energy homeostasis. These experiments will enhance our understanding of the etiology of obesity and metabolic disease ultimately allowing the development of rational clinical interventions for such conditions.

肥胖是世界范围内的一个主要公共健康问题，最近的研究表明，接触a

项目成果

Alterations in DNA methylation of Fkbp5 as a determinant of blood-brain correlation of glucocorticoid exposure.

• DOI: 10.1016/j.psyneuen.2014.03.003
• 发表时间: 2014-06
• 期刊: PSYCHONEUROENDOCRINOLOGY
• 影响因子: 3.7
• 作者: Ewald, Erin R.;Wand, Gary S.;Seifuddin, Fayaz;Yang, Xiaoju;Tamashiro, Kellie L.;Potash, James B.;Zandi, Peter;Lee, Richard S.
• 通讯作者: Lee, Richard S.

Search for common targets of lithium and valproic acid identifies novel epigenetic effects of lithium on the rat leptin receptor gene.

搜索锂和丙戊酸的常见靶标可以确定锂对大鼠瘦素受体基因的新表观遗传作用。

• DOI: 10.1038/tp.2015.90
• 发表时间: 2015-07-14
• 期刊: Translational psychiatry
• 影响因子: 6.8
• 作者: Lee RS;Pirooznia M;Guintivano J;Ly M;Ewald ER;Tamashiro KL;Gould TD;Moran TH;Potash JB
• 通讯作者: Potash JB

Environmental influences that alter the stress circuitry.

改变压力电路的环境影响。

• DOI: 10.1055/s-0032-1316326
• 发表时间: 2012
• 期刊: Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
• 作者: Ismail,N;Sotomayor-Zarate,R;Bale,TL;Blaustein,JD;Gysling,K;Tamashiro,KLK
• 通讯作者: Tamashiro,KLK