Identification of an endogenous PPAR gamma ligand

描述（由申请人提供）：了解脂肪细胞的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。虽然存在许多已知的PPARgamma配体，包括噻唑烷二酮（TZD）类抗糖尿病药物，但实际内源性配体的身份尚不清楚。我们已经开发了一个反馈诱导报告系统的检测和监测的PPARgamma配体活性。在分化脂肪细胞的条件培养基中发现了有效的PPARgamma激活配体活性。该配体活性将通过化学提取、高效液相色谱和质谱法进行分离、表征和鉴定。将表征配体对PPARgamma的特异性。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因子的作用。这项工作将是一项研究计划的基础，该计划将调查天然PPARgamma配体在健康和疾病中的作用。

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.