LOUISIANA COBRE: P3: PPARGAMRNA IN HUMAN ADIPOSE TISSUE DERIVED ADULT STEM CELL

路易斯安那 COBRE：P3：人体脂肪组织来源的成人干细胞中的 PPARGAMRNA

• 批准号: 7610783
• 负责人: ZELPHA ELIZABETH FLOYD
• 金额: $ 15.37万
• 依托单位: LSU PENNINGTON BIOMEDICAL RESEARCH CTR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7610783
• 关键词: Adipocytes; Adipose tissue; Adult; Affect; Age; Aspirate substance; Cardiovascular Diseases; Cell Culture System; Cell Line; Computer Retrieval of Information on Scientific Projects Database; Condition; Development; Fatty acid glycerol esters; Funding; Grant; Human; Hypertension; Institution; Insulin Resistance; Interferon Gamma Receptor Beta Chain; Learning; Ligands; Link; Louisiana; Metabolic syndrome; Modification; Mus; Non-Insulin-Dependent Diabetes Mellitus; Obesity; PPAR gamma; Peroxisome Proliferator-Activated Receptors; Play; Primary Cell Cultures; Regulation; Research; Research Personnel; Resources; Risk Factors; Role; Source; Suction Lipectomy; System; Ubiquitin; Ubiquitin Like Proteins; United States National Institutes of Health; Visceral; adult stem cell; base; clinically relevant; improved; insulin sensitivity; lipid biosynthesis; multicatalytic endopeptidase complex; stem; subcutaneous

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Obesity is a primary risk factor for type 2 diabetes, metabolic syndrome and cardiovascular diseases such as hypertension. Adipose tissues express high levels of the peroxisome proliferator-activated receptor, PPARgamma, the master switch in adipose cell formation. Recent studies show that modulation of PPARgamma levels improves insulin sensitivity and protects against insulin resistance associated with aging. Our studies indicate that regulation of PPARgamma levels by the ubiquitin-proleasome system is linked to control of PPARgamma activity. In addition, we have learned that modification of PPARgamma in the Nterminal AF-1 domain by the ubiquitin-like protein, SUMO-1, affects PPARgamma stability and activity. These studies suggest that modulation of PPARgamma activity by ubiquitin and ubiquitin-like proteins plays an important role in adipogenesis and the development of obesity. However, these studies have used the murine 3T3-L1 adipocyte cell line and there is evidence that adipogenesis may differ between muririe and human systems. In this study, we propose to begin characterizing the relationship between PPARgainma activity and ubiquitin-proteasome-dependent degradation using adult stem cells isolated from human liposuction aspirates. These primary cell cultures, identified as Adipose Derived Adult Stem (ADAS) cells, are an abundant resource that can be reproducibly induced to undergo adipogenesis. We will employ this primary cell culture system to examine the relationship between PPARgamma activity and ubiquitindependent turnover in a human-based, clinically relevant cell line. We hypothesize that ubiquitin-dependent degradation is an important regulator of PPARgamma activity and that PPARgamma is also modified by SUMO-1 in the human ADAS-derived adipocyte. Specific aim 1 will focus on examining the ubiquitylation and SUMOylation status of PPARgamma under basal and ligand-activated conditions. Specific aim 2 will focus on examining PPARgamma turnover in adipocytes derived from subcutaneous and visceral fat depots.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 肥胖是2型糖尿病，代谢综合征和心血管疾病（例如高血压）的主要危险因素。脂肪组织表达高水平的过氧化物酶体增殖物激活的受体Ppargamma，脂肪细胞形成中的主开关。最近的研究表明，ppargamma水平的调节可提高胰岛素敏感性，并防止与衰老相关的胰岛素抵抗。 我们的研究表明，泛素促蛋白 - 促进系统对ppargamma水平的调节与控制ppargamma活性有关。此外，我们了解到，泛素样蛋白SUMO-1对Nterminal AF-1结构域中的ppargamma进行了修饰会影响ppargamma的稳定性和活性。 这些研究表明，泛素和泛素样蛋白对ppargamma活性的调节在脂肪生成和肥胖的发展中起重要作用。但是，这些研究使用了鼠3T3-L1脂肪细胞细胞系，有证据表明，在Muririe和Muririe和 人类系统。在这项研究中，我们建议开始使用从人类吸脂剂中分离出的成年干细胞来表征ppargainma活性与泛素 - 蛋白酶依赖性降解之间的关系。这些原代细胞培养物，被鉴定为脂肪衍生的成年茎（ADAS）细胞，是一种丰富的资源，可重复引起进行脂肪生成。我们将利用这种原代细胞培养系统来检查基于人类的临床相关细胞系中ppargamma活性与泛素独立转移之间的关系。我们假设泛素依赖性降解是ppargamma活性的重要调节剂，并且ppargamma也通过 人类ADA衍生的脂肪细胞中的SUMO-1。具体目标1将重点介绍ppargamma在基础和配体激活条件下的泛素化状态和sumoylation状态。特定的目标2将集中于检查源自皮下和内脏脂肪库的脂肪细胞中的ppargamma周转率。