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

描述(申请人提供)：尽管对双酚A(BPA)造成的健康危害进行了大量研究，但对于其在各种人类疾病中的复杂作用仍未达成共识。这在一定程度上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浓度以及从产前到成年期的长期暴露方案进行的研究。由于双酚A最初被认为只干扰雌激素信号，所以大多数研究集中在它对生殖轴的作用上，而忽视了它对代谢稳态的影响。这项合作研究是纠正这些不足的一次重大尝试。研究人员的实验室是第一批记录双酚A对新生和成年雄性和雌性大鼠的脑下垂体和生殖器官的急性和慢性影响的实验室之一。最近，研究人员报道，NM水平的双酚A显著抑制脂联素的释放，而脂联素是主要的抗糖尿病脂肪因子，同时刺激两种炎性细胞因子--肿瘤坏死因子？和IL-6，来自脂肪组织外植体。在过去的十年里，研究人员在研究脂肪组织功能的许多方面以及肥胖在啮齿动物和人类的代谢综合征中的作用方面积累了相当多的专业知识。总体目标是通过选择性脂肪组织功能的改变来确定慢性双酚A暴露对代谢综合征发展的影响。为此，研究人员将研究以下参数：1)脂肪因子、细胞因子、受体和造脂酶基因表达的调节；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；4)BPA在血液和脂肪组织中的分布。

DESCRIPTION (provided by applicant): 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. The investigators' laboratories were 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 the investigators 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, TNF? and IL-6, from adipose tissue explants. Over the last decade, the investigators 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. 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, the investigators will study the following parameters: 1) 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.