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

背景：尽管有许多关于双酚A(BPA)对健康危害的研究，但共识是 关于它在各种人类疾病中的复杂作用，人们还没有达成一致意见。这部分是由于缺乏 根据良好实验室规范(GLP)使用与环境相关的双酚A浓度进行的研究； 从胎儿期到成年期的慢性暴露养生法。因为双酚A最初被认为只会破坏 雌激素信号，大多数研究集中在它对生殖轴的作用上，而忽视了它的影响。 新陈代谢动态平衡。这项合作研究是纠正这些不足的一次重大尝试。 初步数据：我们的实验室是首批记录双酚A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TNFoc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积累了相当多的专业知识。 啮齿动物和人类的组织功能和肥胖在代谢综合征中的作用。 目的：总体目标是确定慢性双酚A暴露对糖尿病发展的影响。 通过选择性脂肪组织功能改变引起的代谢综合征。为此，我们会研究 以下参数：1)脂肪因子、细胞因子、受体和造脂酶基因的调控 表达，2)脂肪因子和细胞因子的分泌，3)脂肪组织细胞密度的变化，以及4) 双酚A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.