PHYSIOLOGY AND GENETICS OF OBESITY

肥胖的生理学和遗传学

• 批准号: 2452880
• 负责人: J A YANOVSKI
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2452880
• 关键词: African American; adipose tissue; adrenocorticotropic hormone; basal metabolism; beta adrenergic receptor; bioenergetics; biological signal transduction; body composition; caucasian American; child (0-11); clinical research; corticotropin releasing factor; disease /disorder proneness /risk; epidemiology; genetics; glucose metabolism; glucose tolerance test; health behavior; human puberty; human subject; insulin sensitivity /resistance; lipid metabolism; longitudinal human study; noninsulin dependent diabetes mellitus; obesity

Substantial evidence suggests that risk factors and therapeutic approaches derived from the study of Caucasians may not be accurate or effective when applied to individuals of differing ethnicity or race. Many Minority populations in the US, including African American women, have a markedly increased risk from obesity, diabetes mellitus, hypertension, cardiovascular disease, and mortality. This unit investigates the genetic, physiologic, metabolic, and behavioral factors involved in determining weight gain in African Americans and Caucasians. We have found that ACTH levels of African American women, men, and children following ovine CRH are two-fold higher than those of Caucasians, despite no differences in cortisol secretion, that visceral adipose tissue burden in obese African American women is significantly smaller than that of obese Caucasian women, and that less total abdominal, subcutaneous abdominal, and visceral adipose tissue in non-obese African American prepubertal girls than in Caucasian girls, findings that imply the relationship between visceral fat and the complications of obesity are different in African Americans and Caucasians. The susceptibility to weight gain in African American may also result from differences in metabolic efficiency: we have also found that resting energy expenditure is approximately 90 kcal/d less in African American than in Caucasian normal weight girls. Related to the significantly increased prevalence of non-insulin-dependent diabetes mellitus in African Americans compared with Caucasians, this unit has investigated differences in insulin sensitivity, glucose disposal, and fat cell metabolism. In normal weight children we have found a correlation of the subcutaneous adipose tissue depot with insulin levels before and after an oral glucose tolerance test only in African Americans. It is unknown whether these differences are found in obese children or in children at high risk for developing obesity. We will compare body composition, energy expenditure, insulin sensitivity and glucose disposal of obese African American and Caucasian prepubertal obese children and non-obese children of obese African American and Caucasian parents, in order to characterize the timing and nature of factors that may contribute to the prevalence of obesity and its complications. We will also relate serum levels of the body-fat related protein, leptin, to these measures, and characterize the role of the beta-3 adrenergic receptor and leptin signalling pathway in these children's obesity. We will then attempt to follow the growth of these children for the next 15 years. These studies will aid in the rational development of treatments for, and programs for the prevention of, obesity in minority populations.

大量证据表明危险因素和治疗 来自白种人研究的方法可能不准确或 适用于不同民族或种族的个人时有效。 美国的许多少数民族人口，包括非裔美国妇女， 肥胖、糖尿病的风险显着增加， 高血压、心血管疾病和死亡率。 本单位 研究遗传、生理、代谢和行为因素 参与确定非裔美国人和白种人的体重增加。 我们发现非裔美国女性、男性和女性的 ACTH 水平 接受绵羊 CRH 的儿童比接受 CRH 的儿童高两倍 白人，尽管皮质醇分泌没有差异，但内脏 肥胖的非洲裔美国女性的脂肪组织负担显着 比肥胖的白人女性要小，而且总数也更少 腹部、腹部皮下和内脏脂肪组织 非肥胖非裔美国青春期前女孩的比例高于白人女孩， 研究结果暗示内脏脂肪与脂肪之间的关系 非裔美国人和非裔美国人的肥胖并发症有所不同 白种人。 非裔美国人对体重增加的敏感性可能 也是由于代谢效率的差异造成的：我们还发现 静息能量消耗大约减少 90 kcal/d 非洲裔美国人比白人女孩体重正常。 与患病率显着增加有关 非洲裔美国人非胰岛素依赖型糖尿病的比较 该单位研究了与白种人的胰岛素差异 敏感性、葡萄糖处理和脂肪细胞代谢。正常体重时 孩子们，我们发现了皮下脂肪组织的相关性 口服葡萄糖耐量试验前后的胰岛素水平储存 仅在非裔美国人中。 尚不清楚这些差异是否是 发现于肥胖儿童或患有高风险的儿童 肥胖。 我们将比较身体成分、能量消耗、胰岛素敏感性 肥胖的非洲裔美国人和白种人青春期前的葡萄糖处理 肥胖儿童和肥胖非裔美国人的非肥胖儿童 白人父母，为了描述孩子的时间和性质 可能导致肥胖流行的因素及其 并发症。 我们还将与身体脂肪相关的血清水平联系起来 蛋白质，瘦素，对这些措施，并表征其作用 β3 肾上腺素受体和瘦素信号通路在这些 儿童肥胖症。 然后我们将尝试跟踪这些的增长 未来15年的孩子们。这些研究将有助于理性地 开发治疗方法和预防方案， 少数民族人口肥胖。