Role of adipocytes in local and systemic inflammation

描述(由申请人提供)： 拟议的少数民族KO1申请的主要重点是促进Chantal A.Rivera博士的培训和职业发展。里维拉博士选择从事血管生理学的职业，专注于营养和肥胖的后果。博伊德教授、路易斯安那州立大学S健康科学中心分子和细胞生理学主席尼尔·格兰杰博士已同意担任主要导师。此外，我们亦成立了一个由本系资深教员组成的谘询委员会，成员包括德宜胡博士和马修·葛礼贤博士。拟议的发展计划将提供以下内容：1)关于使用活体显微镜和生产嵌合小鼠品系的技术指导。2)微循环生理学的教学性课程。3)负责任地进行研究方面的培训。4)定期与咨询委员会举行会议，以审查进展情况并确保Rivera博士的独立研究事业的成功确立。计划中的研究将集中在脂肪细胞在炎症中的作用。美国60%的成年人现在被归类为超重或肥胖，这一事实突显了研究肥胖的临床意义。越来越多的证据表明，肥胖与一种低级别的全身炎症反应有关，这种反应使宿主容易患上心血管疾病。伴随脂肪细胞生长和增殖的血管炎症的时间进程、程度和潜在机制尚未在体内得到解决。因此，这项建议的一个主要目的是利用活体显微技术系统地描述脂肪组织中微血管所呈现的炎症表型，并验证生长中的脂肪细胞通过产生脂肪因子(如瘦素)在局部微循环中诱导炎症表型的假设。具体地说，将解决以下3个目标：1.建立活体显微技术，以评估饮食和体重增加/脂肪沉积对排出脂肪组织的毛细血管后微静脉中白细胞运输的影响。2.确定饮食脂肪在富含脂肪组织的小静脉中引发炎症反应(黏附分子)的分子决定因素。3.确定瘦素是否参与了小静脉炎症表型的诱导，这些小静脉排出了生长中的脂肪组织。这项拟议的工作将为肥胖伴随的局部和全身炎症反应的起源提供新的见解，并将为申请者在肥胖症和心血管疾病领域发展独立的研究生涯提供基础。

DESCRIPTION (provided by applicant): The primarily focus of the proposed Minority KO1 application is to further the training and career development of Dr. Chantal A. Rivera. Dr. Rivera has chosen to pursue a career in vascular physiology focusing on the consequences of nutrition and obesity. Dr. Neil Granger, Boyd Professor and Chairman of Molecular and Cellular Physiology at LSU-S Health Sciences Center, has agreed to serve as primary mentor. In addition, an advisory committee has also been established consisting of senior faculty members from our department: Dr. Tak Yee Aw and Dr. Mathew Grisham. The proposed development plan would provide the following: 1) technical instruction on the use of intravital microscopy and production of chimeric mouse strains. 2) didactic course work on microcirculation physiology. 3) training in the responsible conduct of research. 4) regular meetings with an advisory committee to reivew progress and ensure the successful establishment of Dr. Rivera's independent research career. The planned research will focus on the role of adipocytes in inflammation. The clinical relevance in studying obesity is underscored by the fact that 60% of adults in the United States are now classified as overweight or obese. There is growing evidence that obesity is associated with a low-grade systemic inflammatory response that predisposes the host to cardiovascular disease. The time-course, magnitude and underlying mechanisms for the vascular inflammation that accompany the growth and proliferation of adipose cells have not been addressed in vivo. Therefore, a major objective of this proposal is to use intravital microscopic techniques to systematically characterize the inflammatory phenotype that is assumed by the microvasculature in adipose tissue and to test the hypothesis that growing adipocytes induce an inflammatory phenotype in the local microcirculation through the production of adipokines (e.g. leptin). Specifically, the following 3 aims will be addressed: 1. Establish intravital microscopic techniques to assess the influence of diet and weight gain/fat deposition on leukocyte trafficking in postcapillary venules that drain adipose tissue. 2. Define the molecular determinants of the inflammatory response (adhesion molecules) elicited in venules of adipose-rich tissue by dietary fat. 3. Determine if leptin contributes to the induction of the inflammatory phenotype in venules that drain growing adipose tissue. The proposed work should provide novel insights into the genesis of the local and systemic inflammatory responses that accompany obesity, and it will provide a foundation for development of an independent research career of the applicant in the areas of obesity and cardiovascular diseases.