Identification of an endogenous PPAR gamma ligand

内源性 PPAR γ 配体的鉴定

• 批准号: 6650437
• 负责人: JONATHAN K HAMM
• 金额: $ 4.64万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-23 至 2004-04-22
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6650437
• 关键词: 3T3 cells; adipocytes; bioenergetics; cell differentiation; cell line; gene expression; high performance liquid chromatography; ligands; mass spectrometry; peroxisome proliferator activated receptor; postdoctoral investigator; protein quantitation /detection; receptor binding; transcription factor; transfection

DESCRIPTION (provided by applicant): Understanding adipocyte differentiation and function is crucial to the treatment of obesity and diabetes. The nuclear receptor PPARgamma is required for these processes. While many known ligands for PPARgamma exist, including the thiazolidinedione (TZD) class of antidiabetic drugs, the identity of the actual endogenous ligand(s) is not known. We have developed a feedback-inducible reporter system for the detection and monitoring of PPARgamma ligand activity. A potent, PPARgamma-activating ligand activity was found in the conditioned medium of differentiating adipocytes. This ligand activity will be isolated, characterized, and identified by chemical extraction, high-performance liquid chromatography, and mass spectrometry. Specificity of the ligand for PPARgamma will be characterized. The physiological regulation and metabolism of the ligand will be investigated, including determining the roles of candidate transcriptional activators of ligand production. This work will be the foundation for a research program investigating the role of natural PPARgamma ligands in health and disease.

描述（由申请人提供）：了解脂肪细胞分化和功能对于治疗肥胖和糖尿病至关重要。这些过程需要核受体ppargamma。尽管存在许多已知的ppargamma配体，但抗糖尿病药物包括噻唑烷二酮（TZD）类别，但实际的内源性配体的身份尚不清楚。我们已经开发了一种反馈诱导的记者系统，用于检测和监测PPARGAMMA配体活动。在区分脂肪细胞的条件培养基中发现了有效的ppargamma激活配体活性。这种配体活性将通过化学提取，高性能液相色谱和质谱法分离，表征和鉴定。配体对ppargamma的特异性将被表征。将研究配体的生理调节和代谢，包括确定配体产生的候选转录激活剂的作用。这项工作将是研究天然ppargamma配体在健康和疾病中的作用的研究计划的基础。