权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Understanding Phagocytosis Within the Adipose Tissue

了解脂肪组织内的吞噬作用

基本信息

批准号：
10557389
负责人：
Brady Barron
金额：
$ 3.31万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2023-08-01
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10557389
关键词：
ANXA5 gene Address Adipocytes Adipose tissue Adult Affect Apoptosis Apoptotic Biological Assay CRISPR/Cas technology Cell Death Cell physiology Cells Cessation of life Coupled Data Dendritic Cells Development Diabetes Mellitus Disease Embryo Epithelial Cells Fatty acid glycerol esters Gastrointestinal tract structure Genes Goals High Fat Diet Homeostasis Human Hypertrophy Immune Immune system In Vitro Individual Infiltration Inflammation Inflammatory Insulin Insulin Resistance Knock-out Knockout Mice Lead Limb Development Lipids Lung Maintenance Mesenchymal Methods Molecular Mus Necrosis Non-Insulin-Dependent Diabetes Mellitus Obesity Pathogenesis Pathology Phagocytes Phagocytosis Phosphatidylserines Play Population Process Production Proteins Reporting Resolution Role Secondary to Stress Surface TNF gene Testing Therapeutic United States Visceral Weight Gain adipocyte differentiation base cell type comorbidity diabetes mellitus therapy feeding improved in vivo inhibitor insulin sensitivity lipid biosynthesis macrophage novel obesity development phosphatidylserine receptor prevent stem cells subcutaneous

项目摘要

PROJECT SUMMARY/ABSTRACT On a daily basis, we turnover billions of apoptotic cells that are removed by phagocytic cells, such as macrophages. The processes of cell death and phagocytic clearance are vital to maintaining homeostasis and are related to many disease pathologies. The adipose tissue has been reported to undergo basal turnover, and during conditions of obesity, apoptotic adipocytes have been shown to increase in mice and humans. This cell death and subsequent macrophage infiltration to clear the dying cells has been described as a key inducer of inflammation and causative in the development of insulin resistance. This inflammation has been specifically attributed to macrophage activity, as depletion of macrophages reduces inflammation and improves insulin sensitivity. Interestingly, these macrophage depletion conditions do not result in the accumulation of dead cells, possibly demonstrating additional phagocytic population(s). In addition to professional phagocytes (such as macrophages), non-professional phagocytes also exist, such as epithelial cells in the digestive tract and lung, or mesenchymal cells during embryonic limb development. These non-professional phagocytes can play vital roles in maintaining homeostasis, yet in the adipose tissue no such population has been defined thus far. Based on preliminary studies, we propose to investigate specific non-professional phagocytic cell populations in the adipose tissue and define how these cells contribute to inflammation, inflammation resolution, and insulin resistance associated with obesity. PtdSer is a lipid specifically exposed on the surface of apoptotic cells and is used by phagocytic cells for clearance. To allows us to better manipulate the phagocytic activity of these cell populations, we will additionally investigate the role of phosphatidylserine (PtdSer) receptors. Understanding cell types, the phagocytic process, and molecular players during homeostasis and adipose tissue inflammation will provide important therapeutic opportunities for obesity.

项目总结/文摘