Nikolić Nataša, Rhedin Magdalena, Rustan Arild C, Storlien Len, Thoresen G Hege, Strömstedt Maria
Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, N-0316 Oslo, Norway.
Biochem Res Int. 2012;2012:714074. doi: 10.1155/2012/714074. Epub 2011 Sep 4.
We investigated the effects of PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α) overexpression on the oxidative capacity of human skeletal muscle cells ex vivo. PGC-1α overexpression increased the oxidation rate of palmitic acid and mRNA expression of genes regulating lipid metabolism, mitochondrial biogenesis, and function in human myotubes. Basal and insulin-stimulated deoxyglucose uptake were decreased, possibly due to upregulation of PDK4 mRNA. Expression of fast fiber-type gene marker (MHCIIa) was decreased. Compared to skeletal muscle in vivo, PGC-1α overexpression increased expression of several genes, which were downregulated during the process of cell isolation and culturing. In conclusion, PGC-1α overexpression increased oxidative capacity of cultured myotubes by improving lipid metabolism, increasing expression of genes involved in regulation of mitochondrial function and biogenesis, and decreasing expression of MHCIIa. These results suggest that therapies aimed at increasing PGC-1α expression may have utility in treatment of obesity and obesity-related diseases.
我们在体外研究了过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）过表达对人骨骼肌细胞氧化能力的影响。PGC-1α过表达增加了人肌管中棕榈酸的氧化速率以及调节脂质代谢、线粒体生物发生和功能的基因的mRNA表达。基础和胰岛素刺激的脱氧葡萄糖摄取减少，这可能是由于PDK4 mRNA上调所致。快肌纤维型基因标记物（MHCIIa）的表达降低。与体内骨骼肌相比，PGC-1α过表达增加了几个基因的表达，这些基因在细胞分离和培养过程中被下调。总之，PGC-1α过表达通过改善脂质代谢、增加参与线粒体功能和生物发生调节的基因表达以及降低MHCIIa表达，提高了培养肌管的氧化能力。这些结果表明，旨在增加PGC-1α表达的疗法可能对肥胖症及肥胖相关疾病的治疗有用。
