Centre of Inflammation and Metabolism and Copenhagen Muscle Research Centre, Section of Molecular and Integrative Physiology, Dept. of Biology, University of Copenhagen, Copenhagen, Denmark.
Am J Physiol Regul Integr Comp Physiol. 2011 Nov;301(5):R1501-9. doi: 10.1152/ajpregu.00775.2010. Epub 2011 Aug 10.
The transcriptional coactivator peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC)-1α plays a role in regulation of several metabolic pathways. By use of whole body PGC-1α knockout (KO) mice, we investigated the role of PGC-1α in fasting, acute exercise and exercise training-induced regulation of key proteins in gluconeogenesis and metabolism in the liver. In both wild-type (WT) and PGC-1α KO mice liver, the mRNA content of the gluconeogenic proteins glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) was upregulated during fasting. Pyruvate carboxylase (PC) remained unchanged after fasting in WT mice, but it was upregulated in PGC-1α KO mice. In response to a single exercise bout, G6Pase mRNA was upregulated in both genotypes, whereas no significant changes were detected in PEPCK or PC mRNA. While G6Pase and PC protein remained unchanged, liver PEPCK protein content was higher in trained than untrained mice of both genotypes. The mRNA content of the mitochondrial proteins cytochrome c (Cyt c) and cytochrome oxidase (COX) subunit I was unchanged in response to fasting. The mRNA and protein content of Cyt c and COXI increased in the liver in response to a single exercise bout and prolonged exercise training, respectively, in WT mice, but not in PGC-1α KO mice. Neither fasting nor exercise affected the mRNA expression of antioxidant enzymes in the liver, and knockout of PGC-1α had no effect. In conclusion, these results suggest that PGC-1α plays a pivotal role in regulation of Cyt c and COXI expression in the liver in response to a single exercise bout and prolonged exercise training, which implies that exercise training-induced improvements in oxidative capacity of the liver is regulated by PGC-1α.
转录共激活因子过氧化物酶体增殖物激活受体（PPAR）-γ共激活因子（PGC）-1α在调节几种代谢途径中发挥作用。通过使用全身 PGC-1α 敲除（KO）小鼠，我们研究了 PGC-1α 在禁食、急性运动和运动训练诱导的肝脏糖异生和代谢关键蛋白调节中的作用。在野生型（WT）和 PGC-1α KO 小鼠的肝脏中，禁食期间糖异生蛋白葡萄糖-6-磷酸酶（G6Pase）和磷酸烯醇丙酮酸羧激酶（PEPCK）的 mRNA 含量上调。在 WT 小鼠中，禁食后丙酮酸羧化酶（PC）保持不变，但在 PGC-1α KO 小鼠中上调。单次运动后，两种基因型的 G6Pase mRNA 均上调，而 PEPCK 或 PC mRNA 无明显变化。虽然 G6Pase 和 PC 蛋白保持不变，但两种基因型的训练小鼠肝脏 PEPCK 蛋白含量均高于未训练小鼠。禁食时，线粒体蛋白细胞色素 c（Cyt c）和细胞色素氧化酶（COX）亚基 I 的 mRNA 含量不变。在 WT 小鼠中，单次运动和长时间运动训练分别引起肝脏 Cyt c 和 COX I 的 mRNA 和蛋白含量增加，但在 PGC-1α KO 小鼠中则没有。禁食或运动均不影响肝脏抗氧化酶的 mRNA 表达，PGC-1α 的缺失也没有影响。总之，这些结果表明，PGC-1α 在响应单次运动和长时间运动训练时，在调节肝脏 Cyt c 和 COXI 表达方面发挥关键作用，这意味着运动训练诱导的肝脏氧化能力的改善受 PGC-1α 调节。
