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: 8478104
• 负责人: Nira Ben-Jonathan
• 金额: $ 27.37万
• 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/8478104
• 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) 造成的健康危害进行了大量研究，但仍达成共识 目前尚未了解其在各种人类疾病中的复杂作用。这部分是由于缺乏 根据良好实验室规范 (GLP) 使用环境相关的 BPA 浓度进行的研究， 以及从产前到成年的长期暴露方案。由于 BPA 最初被认为只会破坏 雌激素信号传导，大多数研究关注其对生殖轴的作用，而忽视其影响 关于代谢稳态。这项合作研究代表了纠正这些缺陷的重大尝试。 初步数据：我们的实验室是最早记录 BPA 对人体的急性和慢性影响的实验室之一。 新生和成年雄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 显着抑制脂联素（主要的抗糖尿病脂肪因子）的释放， 同时刺激脂肪组织外植体释放两种炎症细胞因子 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积累了丰富的专业知识 组织功能以及肥胖在啮齿动物和人类代谢综合征中的作用。 目标：总体目标是确定长期接触 BPA 对发展的影响 通过选择性脂肪组织功能的改变来治疗代谢综合征。为此，我们将研究 以下参数：1）脂肪因子、细胞因子、受体和脂肪生成酶基因的调节 表达，2) 脂肪因子和细胞因子的分泌，3) 脂肪组织细胞结构的变化，以及 4) BPA 在血液和脂肪组织之间的分布。