HEPATIC FLUXES IN PGC-1 ALPHA KO MICE

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。过氧化物酶体增殖物激活受体(PPAR)共激活剂1(PGC-1α)是一种高度可诱导的共激活剂，通过转录激活这些代谢途径中的多个靶点来协调肝脏线粒体脂肪酸氧化、氧化磷酸化和糖异生的能力。在肥胖和糖尿病等代谢性疾病中，PGC-1在肌肉和肝脏中都扮演着重要的角色。在肌肉中，PGC-1的表达在胰岛素抵抗时减少，这与脂肪和碳水化合物氧化之间的不适当切换一致。在肝脏中，PGC-1在糖尿病患者中过度表达，产生能量盈余，能够驱动糖异生和脂肪生成。然而，PGC-1缺乏对这些基因表达的影响，由此导致的通过这些途径对通量的影响，以及对急性禁食的代谢反应，还不完全清楚。

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. The peroxisome proliferator-activated receptor (PPAR) coactivator 1 (PGC-1alpha) is a highly inducible coactivator that coordinates the capacity for hepatic mitochondrial fatty acid oxidation, oxidative phosphorylation, and gluconeogenesis via transcriptional activation of multiple targets in these metabolic pathways. PGC-1 plays an important role in both muscle and liver during metabolic maladies such as obesity and diabetes. In muscle, PGC-1 expression is decreased in insulin resistance consistent with inappropriate switching between fat and carbohydrate oxidation. In liver, PGC-1 is overexpressed in diabetes generating an energy surplus capable of driving gluconeogenesis and lipogenesis. However, the effects of PGC-1 deficiency on the expression of these genes, the resulting effects on flux via these pathways, and the metabolic response to acute fasting is incompletely understood.