Role of adipocytes in local and systemic inflammation

脂肪细胞在局部和全身炎症中的作用

• 批准号: 7102975
• 负责人: CHANTAL A RIVERA
• 金额: $ 13.24万
• 依托单位: LOUISIANA STATE UNIV HSC SHREVEPORT
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7102975
• 关键词: adipocytes; adipose tissue; biological signal transduction; body composition; capillary; cell migration; dietary lipid; genetically modified animals; inflammation; intravital microscopy; laboratory mouse; laboratory rat; leptin; leukocyte adhesion molecules; microcirculation; nutrition related tag; technology /technique development; vascular endothelium; weight gain

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.

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。 Rivera 博士选择从事血管生理学职业，重点研究营养和肥胖的后果。路易斯安那州立大学南健康科学中心博伊德教授兼分子和细胞生理学主席 Neil Granger 博士已同意担任主要导师。此外，还成立了一个由我们系的高级教师组成的咨询委员会：Tak Yee Aw博士和Mathew Grisham博士。拟议的开发计划将提供以下内容：1）关于使用活体显微镜和嵌合小鼠品系生产的技术指导。 2）微循环生理学教学课程。 3）负责任地进行研究的培训。 4) 与顾问委员会定期举行会议，审查进展情况并确保 Rivera 博士的独立研究生涯的成功建立。计划的研究将集中于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，这一事实凸显了肥胖研究的临床意义。越来越多的证据表明，肥胖与低度全身炎症反应有关，使宿主易患心血管疾病。伴随脂肪细胞生长和增殖的血管炎症的时程、程度和潜在机制尚未在体内得到解决。因此，该提案的一个主要目标是利用活体显微镜技术来系统地表征脂肪组织中微脉管系统所呈现的炎症表型，并检验生长的脂肪细胞通过产生脂肪因子（例如瘦素）在局部微循环中诱导炎症表型的假设。具体而言，将解决以下 3 个目标： 1. 建立活体显微镜技术来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. 定义膳食脂肪在富含脂肪组织的小静脉中引起的炎症反应（粘附分子）的分子决定因素。 3. 确定瘦素是否有助于诱导排出正在生长的脂肪组织的小静脉中的炎症表型。拟议的工作应该为伴随肥胖的局部和全身炎症反应的起源提供新的见解，并将为申请人在肥胖和心血管疾病领域的独立研究事业的发展奠定基础。