Role of adipocytes in local and systemic inflammation

点击翻译按钮获取中文摘要

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.