ENDOGENOUS LIGANDS FOR PPAR-GAMMA

PPAR-γ 的内源性配体

• 批准号: 2900101
• 负责人: HAROLD M WRIGHT
• 金额: $ 3.84万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2900101
• 关键词: adipose tissue; cell differentiation; chimeric proteins; fatty acid metabolism; gas chromatography; high performance liquid chromatography; histogenesis; hormone receptor; ligands; lipids; obesity; prostaglandins; receptor binding; thin layer chromatography; transcription factor; yeast two hybrid system

The nuclear hormone receptor, peroxisome proliferator activated receptor gamma (PPAR gamma) is expressed preferentially in adipose tissue, where it is responsible for coordinating adipocyte gene expression and differentiation. Adipocytes are an important component of the energy equilibrium of vertebrate organisms; providing an abundant energy reserve upon demand. The excessive development of adipose tissue results in obesity, which is a significant risk factor for non-insulin- dependent diabetes mellitus and a number of cardiovascular diseases. Fatty acids, such as arachidonic acid (AA) are known to induce adipogenesis, however their mechanism of action is not known. Recently, an AA metabolite, 15-deoxy-delta-12,14-prostaglandin J2 (15d-PGJ2), has been shown to be a ligand for PPAR gamma. Whether 15d-PGJ2 is the physiologically relevant ligand for PPAR gamma is not certain and thus raises the possibility that other lipid metabolites may serve as endogenous ligands for PPAR gamma. Therefore, the primary objective of this research proposal is to determine endogenous ligand(s) for PPAR gamma and to investigate the physiological and biochemical mediators of their release. The specific aims involve: 1; Characterization of the major fatty acids/metabolites in 3T3-F442A preadipocytes. 2. Elucidation of the fatty acids/metabolites that stimulate PPAR gamma and induce adipocyte differentiation. 3. Determination as to whether agonists known to induce adipocyte differentiation (eg. IGF-1, glucocorticoids), exert their actions via the release of endogenous fatty acids/metabolites, and if so investigate the second messenger systems they employ.

核激素受体，过氧化物酶体增殖物激活受体 γ（PPAR γ）优先在脂肪组织中表达，其中 它负责协调脂肪细胞基因表达， 分化 脂肪细胞是能量的重要组成部分 脊椎动物有机体的平衡;提供充足的能量 储备需求。 脂肪组织的过度发育 导致肥胖，这是非胰岛素的一个重要风险因素， 依赖性糖尿病和一些心血管疾病。 已知脂肪酸，如花生四烯酸（AA）诱导 脂肪形成，然而它们的作用机制尚不清楚。 最近， AA代谢物15-脱氧-δ-12，14-前列腺素J2（15 d-PGJ 2） 是过氧化物酶体增殖物激活受体γ的配体。 15 d-PGJ 2是否为 PPAR γ的生理学相关配体是不确定的，因此 增加了其他脂质代谢物可能作为 PPAR γ的内源性配体。 因此， 本研究计划确定过氧化物酶体增殖物激活受体的内源性配体 γ和调查的生理和生化介质， 他们的释放 具体目标包括：1;表征的 3 T3-F442 A前脂肪细胞中的主要脂肪酸/代谢物。 2. 阐明刺激PPAR γ的脂肪酸/代谢物， 诱导脂肪细胞分化。 3.确定是否 已知诱导脂肪细胞分化的激动剂（例如，IGF-1， 糖皮质激素），通过释放内源性 脂肪酸/代谢物，如果是这样，研究第二信使 他们使用的系统。

项目成果

Comparison of radial 4D Flow-MRI with perivascular ultrasound to quantify blood flow in the abdomen and introduction of a porcine model of pre-hepatic portal hypertension.

• DOI: 10.1007/s00330-017-4862-4
• 发表时间: 2017-12
• 期刊: European radiology
• 影响因子: 5.9
• 作者: Frydrychowicz A;Roldan-Alzate A;Winslow E;Consigny D;Campo CA;Motosugi U;Johnson KM;Wieben O;Reeder SB
• 通讯作者: Reeder SB