Bisphenol A and the Metabolic Syndrome: Focus on Adipose Tissue Functions

双酚 A 和代谢综合征：关注脂肪组织功能

• 批准号: 8334555
• 负责人: Nira Ben-Jonathan
• 金额: $ 28.26万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-19 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8334555
• 关键词: Acute; Adipocytes; Adipose tissue; Adult; Affect; Animal Model; Animals; Architecture; Arkansas; Biological Assay; Blood; Body Weight; Cardiovascular Diseases; Cell Count; Cellularity; Chronic; Complex; Consensus; Cytokine Receptors; Data; Decision Making; Deposition; Development; Diabetes Mellitus; Diet; Dose; Energy Intake; Environment; Enzyme Gene; Enzymes; Estrogens; Event; Exposure to; Fasting; Fatty acid glycerol esters; Female; Gene Expression; Genes; Goals; Health Hazards; Histocytochemistry; Homeostasis; Hormone Receptor; Hormones; Human; Immunoassay; Infiltration; Inflammatory; Instruction; Interleukin-6; Laboratories; Leptin; Link; Magnetic Resonance Imaging; Measures; Mesentery; Metabolic; Metabolic syndrome; Monocyte Chemoattractant Protein-1; Neonatal; Nonesterified Fatty Acids; Obesity; Organ; Pituitary Gland; Pituitary Hormones; Play; Population; Prolactin; Promoter Regions; Puberty; RNA; Rattus; Regimen; Regulation; Reporting; Retroperitoneal Space; Reverse Transcriptase Polymerase Chain Reaction; Rodent; Role; Serum; Signal Transduction; Skeletal Muscle; Solid; Somatotropin; Time; Tissues; Transcription factor genes; Tumor Necrosis Factor-alpha; Vascularization; adipokines; adiponectin; analytical method; bisphenol A; cytokine; diabetic; good laboratory practice; human disease; lipoprotein triglyceride; liquid chromatography mass spectroscopy; macrophage; male; mature animal; meetings; prenatal; reproductive; reproductive axis; response; subcutaneous; young adult

Background: Despite numerous studies on health hazards caused by Bisphenol A (BPA), consensus has not been reached as to its complex roles in various human diseases. This is partially due to a dearth of studies done under Good Laboratory Practices (GLP) using environmentally relevant BPA concentrations, and chronic exposure regimens from prenatal to adulthood. As BPA was originally thought to only disrupt estrogen signaling, most studies focused on its actions on the reproductive axis while overlooking its effects on metabolic homeostasis. This collaborative study represents a major attempt to rectify these deficiencies. Preliminary Data: Our laboratory was among the first to document both acute and chronic effects of BPA on the pituitary and reproductive organs of neonatal and adult male and female rats. More recently we reported that BPA at nM levels significantly inhibited the release of adiponectin, the major anti-diabetic adipokine, while stimulating the release of two inflammatory cytokines, TNFoc and IL-6, from adipose tissue explants. Over the last decade, our laboratory developed considerable expertise in studying many aspects of adipose tissue functions and the role of obesity in the metabolic syndrome in both rodents and humans. Objectives: The overall objective is to determine the effects of chronic BPA exposure on the development of the metabolic syndrome via alterations in selective adipose tissue functions. To this end, we will study the following parameters: 1) the regulation of adipokine, cytokine, receptor and lipogenic enzymes gene expression, 2) secretion of adipokines and cytokines, 3) changes in adipose tissue cellularity, and 4) the distribution of BPA between blood and adipose tissue.

背景：尽管对双酚A（BPA）引起的健康危害的许多研究，但共识已有 关于其在各种人类疾病中的复杂作用尚未达到。这部分是由于缺乏 使用与环境相关的BPA浓度进行的良好实验室实践（GLP）进行的研究， 以及从产前到成年的慢性暴露方案。因为BPA最初被认为只是破坏 雌激素信号传导，大多数研究都集中在其对生殖轴上的作用，同时忽视其效果 在代谢稳态上。这项协作研究代表了纠正这些缺陷的主要尝试。 初步数据：我们的实验室是最早记录BPA急性和慢性影响的实验室之一 新生儿和成年男性和雌性大鼠的垂体和生殖器官。最近我们报道了 NM水平的BPA显着抑制了脂联素的释放，脂联素（主要的抗糖尿病脂蛋白）， 同时，从脂肪组织外植体释放了两种炎性细胞因子TNFOC和IL-6。 在过去的十年中，我们的实验室在研究脂肪的许多方面方面发展了大量专业知识 组织功能和肥胖在啮齿动物和人类中代谢综合征中的作用。 目标：总体目标是确定慢性BPA暴露对发展的影响 代谢综合征通过选择性脂肪组织功能的改变。为此，我们将研究 以下参数：1）脂肪因子，细胞因子，受体和脂肪生物基因的调节 表达，2）分泌脂肪因子和细胞因子，3）脂肪组织细胞的变化，4） 血液和脂肪组织之间BPA的分布。