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

背景：尽管有许多关于双酚A（BPA）引起的健康危害的研究， 尚未达到其在各种人类疾病中的复杂作用。部分原因是缺乏 根据良好实验室规范（GLP）使用环境相关BPA浓度进行的研究， 以及从产前到成年的长期接触方案。由于BPA最初被认为只会破坏 雌激素信号，大多数研究都集中在其对生殖轴的作用，而忽略了它的影响 关于代谢稳态。这项合作研究是纠正这些缺陷的一次重大尝试。 初步数据：我们的实验室是第一个记录BPA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。最近我们报道说 BPA在nM水平显著抑制脂联素的释放，脂联素是主要的抗糖尿病脂肪因子， 同时刺激脂肪组织外植体释放两种炎性细胞因子TNF α c和IL-6。 在过去的十年里，我们的实验室在研究脂肪的许多方面发展了相当多的专业知识， 组织功能和肥胖在啮齿动物和人类代谢综合征中的作用。 目的：总体目标是确定慢性BPA暴露对以下发育的影响： 通过选择性脂肪组织功能的改变来治疗代谢综合征。为此，我们会研究 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控 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，和4）脂肪细胞的增殖。 BPA在血液和脂肪组织中的分布。

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.