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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：
10251932
负责人：
Brady Barron
金额：
$ 3.45万
依托单位：
UNIVERSITY OF VIRGINIA
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 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10251932
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/antagonist 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/摘要每天，我们周转数十亿个凋亡细胞，这些细胞被吞噬细胞清除，如巨噬细胞细胞死亡和吞噬清除过程对维持体内平衡至关重要，与许多疾病病理学有关。据报道，脂肪组织经历基础周转，并且在在肥胖症的情况下，凋亡脂肪细胞已显示在小鼠和人中增加。这种细胞死亡和随后巨噬细胞浸润以清除垂死细胞被描述为炎症的关键诱导物，导致胰岛素抵抗的发展。这种炎症特别归因于巨噬细胞活性，因为巨噬细胞的消耗减少了炎症并提高了胰岛素敏感性。有趣的是，这些巨噬细胞耗竭条件不导致死细胞的积累，可能证明了额外的吞噬细胞群。除了专职吞噬细胞（如巨噬细胞），也存在吞噬细胞，例如消化道和肺中的上皮细胞，或胚胎发育期间的间充质细胞。肢体发育这些非专职吞噬细胞在维持体内平衡方面发挥着重要作用，但在脂肪组织迄今为止还没有定义这样的群体。根据初步研究，我们建议调查脂肪组织中特定的非专职吞噬细胞群，并确定这些细胞如何有助于炎症、炎症消退和与肥胖相关的胰岛素抵抗。PtdSer是一种脂质，暴露在凋亡细胞的表面上，并被吞噬细胞用于清除。让我们更好地操纵这些细胞群的吞噬活性，我们将另外研究磷脂酰丝氨酸（PtdSer）受体。了解细胞类型、吞噬过程和分子参与者在体内平衡和脂肪组织炎症期间将为肥胖提供重要的治疗机会。