HEPATIC FLUXES IN PGC-1 ALPHA KO MICE

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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.