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: 7720513
• 负责人: ZELPHA ELIZABETH FLOYD
• 金额: $ 15.5万
• 依托单位: LSU PENNINGTON BIOMEDICAL RESEARCH CTR
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7720513
• 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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 肥胖是2型糖尿病、代谢综合征和高血压等心血管疾病的主要危险因素。脂肪组织表达高水平的过氧化物酶体增殖物激活受体PPARγ，它是脂肪细胞形成的主开关。最近的研究表明，调节PPARγ水平可以改善胰岛素敏感性，防止与衰老相关的胰岛素抵抗。我们的研究表明，泛素-前列腺体系统对PPAR伽马水平的调节与PPAR伽马活性的控制有关。此外，我们还了解到，泛素样蛋白SUMO-1对N端AF-1结构域的PPARGamma进行修饰会影响PPARGamma的稳定性和活性。 这些研究表明，泛素和泛素样蛋白对PPAR-γ活性的调节在脂肪形成和肥胖的发生发展中起着重要作用。然而，这些研究使用了小鼠3T3-L1脂肪细胞系，有证据表明，小鼠和小鼠的脂肪生成可能不同。 人类系统。在这项研究中，我们建议开始利用从人吸脂抽吸物中分离的成人干细胞来表征PPAR活性和泛素蛋白酶体依赖的降解之间的关系。这些原代培养的细胞被鉴定为脂肪来源的成体干细胞(ADAS)，是一种丰富的资源，可以通过重复诱导进行脂肪生成。我们将使用这个原代细胞培养系统来检验PPAR-γ活性和临床相关的人类细胞系中普遍独立的周转之间的关系。我们假设泛素依赖的降解是PPARGamma活性的重要调节因子，并且PPARGamma也被 人ADAS来源的脂肪细胞中的SUMO-1。具体目标1将重点研究在基础条件和配体激活条件下PPARγ的泛素化和SUMO化状态。具体目标2将重点研究来自皮下和内脏脂肪库的脂肪细胞中PPAR伽马的周转情况。