Role of adipose tissue cellular composition on healthy metabolism

脂肪组织细胞组成对健康代谢的作用

基本信息

批准号：
10046434
负责人：
MICHAL Mateusz MASTERNAK
金额：
$ 2.1万
依托单位：
UNIVERSITY OF CENTRAL FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-11-01 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10046434
关键词：
Activities of Daily Living Adipocytes Adipose tissue Aging Animal Model Animals Anti-Inflammatory Agents Body fat Caloric Restriction Cardiovascular Diseases Cell physiology Cells Diabetes Mellitus Diet Disease Dwarfism Endocrine Equilibrium Excision Exhibits FOXP3 gene Fatty acid glycerol esters Genetic Goals Health Hormonal Human Immune Infiltration Inflammation Inflammatory Insulin Resistance Interleukin-6 Laboratories Life Life Style Link Longevity Malignant Neoplasms Mesenchymal Stem Cells Metabolic Metabolism MicroRNAs Molecular Mus Obesity Phenotype Physiological Physiology Play Population Predisposition Prevalence Production Race Rattus Regulatory T-Lymphocyte Research Role Siblings Somatotropin T-Lymphocyte TNF gene Testing Visceral Visceral fat adipokines comorbidity cytokine fasting glucose functional plasticity glucose tolerance healthspan healthy aging human model improved insight insulin sensitivity insulin signaling macrophage prevent self-renewal stem cell division stem cell population

项目摘要

The long-term goal of our research is to determine the mechanism responsible for beneficial alteration of the physiology and cellular function of adipose tissue, which improves insulin signaling function, suppresses systemic inflammation, and promotes healthy aging. Several studies with mice, rats, and humans have indicated that obesity causes insulin resistance and has negative effects on longevity. However, our studies with long-living Ames dwarf mice indicate that these growth hormone deficient animals have altered functions of adipose tissue that promote healthy phenotypes regardless of a predisposition to obesity during aging. Following our previous studies, we are determined to discover the mechanism responsible for high insulin sensitivity, low inflammation, and healthy aging. We propose the general hypothesis that the quality (cellular composition), and not quantity, of white adipose tissue (WAT) regulates high insulin sensitivity, protects against systemic inflammation, and promotes healthy aging. In our proposed studies we will (i) study whether WAT residing Treg cells help maintain a healthy immune balance and low inflammation by promoting mesenchymal stem cells (MSCs) self-renewal, (ii) investigate the consequences of Treg cells depletion on metabolism and inflammation, (iii) elucidate the mechanism responsible for self-renewal of adipose derived MSCs in df/df mice, and (iv) determine the regulatory role of Treg cells and MSCs on the endocrine function of adipocytes. We propose the following specific aims: Aim 1. To determine the role of WAT residing Treg cells and MSCs on insulin sensitivity and inflammatory status in df/df and N/df mice during aging: (A) investigate if expansion of Treg cells will promote self-renewal of WAT residing MSCs and healthy insulin sensitivity, and (B) study whether depletion of Treg cells will have a negative effect on insulin sensitivity, inflammation, and self-renewal of WAT residing MSCs populations. Aim 2. To determine the molecular mechanism by which fat-resident and infiltrating Treg cells and MSCs regulate the endocrine activity of adipocytes.

我们研究的长期目标是确定负责改变的机制脂肪组织的生理和细胞功能（改善胰岛素信号传导功能）抑制系统性炎症，并促进健康的衰老。对小鼠，大鼠和人类的几项研究表明，肥胖会引起胰岛素抵抗和对寿命有负面影响。但是，我们对悠久的AMES矮小小鼠的研究表明生长激素缺乏动物改变了促进健康表型的脂肪组织功能不论衰老期间肥胖的易感性。遵循我们先前的研究，我们决心发现负责高胰岛素敏感性，低炎症和健康衰老的机制。我们提出了一个总体假设，即质量（细胞组成），而不是白色脂肪组织（WAT）的数量调节高胰岛素敏感性，可预防系统性炎症，并促进健康的衰老。在我们提出的研究中，我们将（i）研究居住在Treg细胞的WAT是否有助于维持健康的免疫力通过促进间充质干细胞（MSC）自我更新来平衡和低炎症，（ii）研究 Treg细胞耗尽对代谢和炎症的后果，（iii）阐明了机制负责DF/DF小鼠中脂肪衍生的MSC的自我更新，（iv）确定调节作用 Treg细胞和MSC在脂肪细胞的内分泌功能上。我们提出以下具体目标：目的1。确定居住在Treg细胞和MSC对胰岛素敏感性和炎症性的WAT的作用衰老期间DF/DF和N/DF小鼠的状态：（a）调查Treg细胞的膨胀是否会促进自我更新驻留MSC和健康胰岛素敏感性的WAT，（B）研究Treg细胞的耗竭是否会具有对胰岛素敏感性，炎症和自我更新的负面影响。目的2。确定脂肪和浸润Treg细胞和MSC的分子机制调节脂肪细胞的内分泌活性。