Impact of peripubertal exposure to xenohormones on fat distribution and cytokines

青春期前后暴露于异激素对脂肪分布和细胞因子的影响

• 批准号: 7786563
• 负责人: FRANK M BIRO
• 金额: $ 28.43万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7786563
• 关键词: Address; Adolescent; Adult; Age; Age at Menarche; Aromatase; Biochemical; Biochemical Process; Biological; Biological Markers; Biological Phenomena; Body Composition; Body fat; Bone Density; Bone Mineral Contents; Breast Cancer Prevention; Breast Cancer Risk Factor; Childhood; Data; Deposition; Development; Dual-Energy X-Ray Absorptiometry; Endocrine Disruptors; Environmental Exposure; Estrogens; Event; Exposure to; Fasting; Fatty acid glycerol esters; Female; Glucose; Growth; Growth and Development function; Height; High Density Lipoprotein Cholesterol; Hypertension; Inflammatory; Insulin; Insulin Resistance; Interleukin-6; LDL Cholesterol Lipoproteins; Lead; Leptin; Link; Lipids; Literature; Longitudinal Studies; Measurement; Mediating; Menarche; Metabolic; Metabolic syndrome; Morbidity - disease rate; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Osteocalcin; Overweight; Pattern; Physical Examination; Physiological; Phytoestrogens; Predisposition; Prevalence; Preventive Intervention; Production; Protocols documentation; Proxy; Puberty; Race; Research; Research Personnel; Risk; Risk Factors; Risk Marker; Serum; Severities; Subgroup; Teenagers; Time; Triglycerides; Urine; Visceral; Weight; Woman; adipokines; adiponectin; adverse outcome; base; bone; cohort; cytokine; early thelarche; girls; inflammatory marker; malignant breast neoplasm; mortality; obesity in children; phthalates; pubertal timing; public health relevance

DESCRIPTION (provided by applicant): Puberty is a dynamic period which includes physiologic and biochemical changes, and may serve as a window of susceptibility for adult morbidity and mortality. For example, the majority of bone mineral content in females is deposited during the teen years, and the relationship between greater bone mineral density and breast cancer is established. Puberty is also a time of dramatic changes in body composition, with a rise in insulin resistance. The deposition of visceral fat is believed to increase the risk of metabolic complications of obesity, but little is known about factors in childhood that impact deposition of visceral fat. Certain environmental exposures (e.g., endocrine disruptors) impact body composition as well as timing of puberty. Studies in adults describe the relationship between breast cancer, obesity, insulin resistance, and adipokines. Leptin and pro-inflammatory cytokines induce aromatase activity and production of estrogen, as well as lead to insulin resistance, whereas adiponectin has an inverse relationship with breast cancer. We propose to utilize a unique existing cohort of racially and ethnically diverse girls who have been followed longitudinally from ages 6 and 7. These girls have had serial examinations over 2-4 years, including height, weight, and assessment of pubertal maturation, as well as urine biomarkers obtained at baseline. Our aims are: to evaluate the relationship between the accumulation of fat during pubertal maturation by race and timing of puberty, and exposure to phthalates and phytoestrogens; and evaluate the longitudinal relationship between the early exposures to endocrine disruptors, timing of pubertal maturation, development of insulin resistance, and changes in leptin and adiponectin. This proposal will incorporate anthropometric and maturation data from the previous longitudinal study with earlier biomarker data, to current assessments of: body composition, regional fat distribution, and bone density; fasting insulin, glucose, and lipid profile; the adipokines leptin and adiponectin; and an inflammatory marker, IL-6. Additionally, one subgroup has had insulin and glucose levels obtained at baseline, and we propose to add analyses of stored sera from that time for analysis of leptin and adiponectin levels. This will allow us to better understand the relationships between timing of puberty, exposures to endocrine disruptors, pubertal body composition changes, and underlying mechanisms of insulin resistance with obesity and the metabolic syndrome. This study may help to inform interventions for prevention of breast cancer and the metabolic consequences of obesity. PUBLIC HEALTH RELEVANCE: The cohort of girls in this protocol have been followed longitudinally from ages 6 and 7 with physical examinations and measurement of environmental and dietary exposures. The additional studies in this proposal will allow the investigators to observe changes in body composition, bone content, and biochemical processes during puberty, a crucial period of growth and development.

描述（由申请人提供）：青春期是一个动态时期，包括生理和生化变化，可以作为成人发病率和死亡率易感性的窗口。例如，在青少年时期，女性中的大多数骨矿物质含量都沉积，并且建立了更大的骨矿物质密度与乳腺癌之间的关系。青春期也是人体成分发生巨大变化的时代，胰岛素抵抗的升高。据信内脏脂肪的沉积会增加肥胖代谢并发症的风险，但对影响内脏脂肪沉积的童年因素知之甚少。某些环境暴露（例如，内分泌破坏者）会影响身体成分以及青春期的时机。成人的研究描述了乳腺癌，肥胖，胰岛素抵抗和脂肪因子之间的关系。瘦素和促炎细胞因子诱导芳香酶的活性和雌激素的产生，并导致胰岛素抵抗，而脂联素与乳腺癌有反比关系。我们建议利用独特的现有种族和种族多样的女孩队列，这些女孩在6岁和7岁时都受到了纵向的关注。这些女孩在2-4岁以上进行了串行检查，包括对青春期成熟的身高，体重和评估，以及在基线上获得的尿液生物标志物。我们的目的是：评估青春期成熟期间脂肪积累与青春期时机的关系，以及暴露于邻苯二甲酸酯和植物雌激素之间的关系；并评估早期暴露于内分泌破坏者的纵向关系，青春期成熟的时机，胰岛素抵抗的发展以及瘦素和脂联素的变化。该提案将结合先前纵向研究的人体测量和成熟数据，并具有早期的生物标志物数据，并对当前的评估：身体组成，区域脂肪分布和骨密度；禁食胰岛素，葡萄糖和脂质谱；脂肪因子瘦素和脂联素；和炎症标记，IL-6。此外，一个亚组具有在基线时获得的胰岛素和葡萄糖水平，我们建议从那时起储存的血清分析瘦素和脂联素水平。这将使我们能够更好地了解青春期时机，对内分泌干扰物的暴露时间，青春期身体成分的变化以及肥胖症胰岛素抵抗的潜在机制与代谢综合征之间的关系。这项研究可能有助于为预防乳腺癌的干预措施和肥胖的代谢后果提供信息。 公共卫生相关性：该协议中的女孩队列已从6岁和7岁的年龄进行纵向遵循，并进行了身体检查以及对环境和饮食暴露的测量。该提案中的其他研究将使研究人员能够观察到青春期期间人体成分，骨骼含量和生化过程的变化，这是至关重要的生长和发育时期。