HEPATIC FLUXES IN PGC-1 ALPHA KO MICE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。过氧化物酶体增殖物激活受体（过氧化物酶体增殖物激活受体）辅激活因子1（PGC-1 α）是一种高度诱导的辅激活因子，通过转录激活这些代谢途径中的多个靶点，协调肝脏线粒体脂肪酸氧化、氧化磷酸化和肝异生的能力。PGC-1在肥胖和糖尿病等代谢疾病中在肌肉和肝脏中起着重要作用。在肌肉中，PGC-1表达在胰岛素抵抗中降低，这与脂肪和碳水化合物氧化之间的不适当转换一致。在肝脏中，PGC-1在糖尿病中过表达，产生能够驱动脂肪生成和脂肪生成的能量盈余。然而，PGC-1缺乏对这些基因表达的影响，通过这些途径对通量的影响，以及对急性禁食的代谢反应尚不完全清楚。

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.