IDENTIFICATION OF THE PHYSIOLOGICALLY RELEVANT ENDOGENOUS LIGAND FOR PPAR?

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。 PPAR？是一种核受体，可被治疗人类血脂紊乱的药物激活 新陈代谢。其内源性配体尚不清楚。依赖PPAR的基因表达受损 在组织特异性脂肪酸合成酶(Fas)失活的小鼠中， 棕榈酸，16：0)，表明Fas参与了PPAR？细胞配体的产生。 在这里，我们展示了依赖于Fas的特定磷脂与野生型结合的存在 PPAR是从小鼠肝细胞核中分离得到的。依赖于Fas的同源结合 DNA结合缺陷(DBD)PPAR的分子种类也被证明。在诱导Fas活性的条件下，磷脂与野生型和DBD PPAR的结合增加，并在几分钟内被全身注射PPAR激动剂所取代。

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. PPAR¿ is a nuclear receptor activated by drugs to treat human disorders of lipid metabolism. Its endogenous ligand is unknown. PPAR¿-dependent gene expression is impaired in mice with tissue-specific inactivation of fatty acid synthase (FAS, which synthesizes palmitate, 16:0), suggesting that FAS is involved in generation of the PPAR¿ cellular ligand. Here we demonstrate the FAS-dependent presence of a specific phospholipid bound to wild type PPAR¿ isolated from the nuclear fraction of mouse liver. FAS-dependent binding of the same Molecular species was also demonstrated for DNA binding-defective (DBD) PPAR¿. Phospholipid binding to wild type as well as DBD PPAR¿ was increased under conditions that induce FAS activity and displaced within minutes by systemic injection of a PPAR¿ agonist.