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: 7417438
• 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/7417438
• 关键词: Address; Adherent Culture; Adipocytes; Adipose tissue; Adult; Advisory Committees; Area; Attention; Blood Circulation; Blood Vessels; Cardiovascular Diseases; Cell Adhesion; Cell Adhesion Molecules; Cell physiology; Chairperson; Condition; Conditioned Culture Media; Deposition; Development; Development Plans; Diabetes Mellitus; Diet; Dietary Fats; Endothelial Cells; Endothelium; Ensure; Epidemic; Faculty; Fatty acid glycerol esters; Foundations; Genes; Goals; Growth; Health Sciences; Hypertension; Inflammation; Inflammatory; Inflammatory Response; Instruction; Intercellular adhesion molecule 1; Kinetics; Leptin; Leukocyte Trafficking; Leukocytes; Measurement; Mediating; Mentors; Mesentery; Microcirculation; Microscopic; Minority; Molecular; Mouse Strains; Mus; Obesity; Overweight; P-Selectin; Pathology; Phenotype; Physiology; Production; Rattus; Recombinants; Research; Rodent; Rodent Model; Role; Series; Source; Techniques; Testing; Time; Tissues; Training; United States; Vascular Cell Adhesion Molecule-1; Visceral; Weight Gain; Work; adipokines; base; career; clinically relevant; cytokine; feeding; in vivo; insight; intravital microscopy; leptin receptor; macrophage; member; monocyte; mouse model; mutant; neutralizing antibody; novel; nutrition; postcapillary venule; professor; research study; saturated fat; vascular inflammation; venule

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）： 拟议的少数族裔KO 1申请的主要重点是进一步培训和Chantal A博士的职业发展。里维拉。里维拉博士选择从事血管生理学的职业，重点研究营养和肥胖的后果。尼尔格兰杰博士，博伊德教授和LSU-S健康科学中心的分子和细胞生理学主席，已同意担任主要导师。此外，还成立了一个咨询委员会，由我们系的高级教职员工：Tak Yee Aw博士和Mathew Grisham博士组成。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生产嵌合小鼠品系的技术指导。2)微循环生理学的教学课程。3)培训负责任的研究行为。4)与咨询委员会定期举行会议，以审查进展情况，并确保里维拉博士的独立研究事业的成功建立。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，这一事实强调了研究肥胖的临床相关性。越来越多的证据表明，肥胖与低级别的全身炎症反应有关，这种炎症反应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间过程、程度和潜在机制尚未在体内得到解决。因此，本提案的一个主要目的是使用活体显微镜技术来系统地表征脂肪组织中微血管系统所假定的炎症表型，并测试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，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.定义由膳食脂肪引起的富含脂肪组织的小静脉中炎症反应的分子决定因素（粘附分子）。3.确定瘦素是否有助于在排出生长中的脂肪组织的小静脉中诱导炎性表型。拟议的工作应该提供新的见解，伴随肥胖症的局部和全身炎症反应的起源，它将提供一个基础，为申请人在肥胖症和心血管疾病领域的独立研究生涯的发展。