The Oxidative Capacity of Skeletal Muscle: Effects of Genotype, High-Fat Diet and Physical Activity

The primary purpose of the current dissertation was to investigate the effects of genotype, high-fat diet and physical activity on constituents of skeletal muscle oxidative capacity. More specifically we aimed to: 1) determine the characteristics of inherited oxidative capacity in rat skeletal muscle and investigate the gene expression profiles that could connect aerobic exercise capacity with metabolic disease risk factors; 2) investigate the effects of high-fat diet (HFD) and voluntary running on capillarization in skeletal muscle of mice; 3) to develop a system that is able to quantify the physical activity of sedentary and voluntary running mice; 4) to study skeletal muscle adaptation mechanisms after resistance exercise (RE) or endurance exercise (EE) by investigating acute gene expression responses of PGC-1 isoforms in humans. The rats with low inherited oxidative capacity (LCRs) had higher levels of metabolic disease risk factors. The rats with high inherited oxidative capacity (HCRs) had higher resting metabolic rate and levels of voluntary activity, as well as higher capillarization and mitochondrial area in their skeletal muscles. In addition, HCRs had higher expression of genes related to aerobic energy production pathways and branched chain amino acid degradation. Furthermore, the analyses showed that the expression of genes related to oxidative phosphorylation and lipid metabolism was associated with whole-body glucose balance. Both HFD and voluntary running induced capillarization in the skeletal muscle of mice. HFD increased protein level of angiogenic factor VEGF-A in muscle tissue and mRNA levels of VEGF-A and HIF-1α in endothelial cells. Calibration measurements and long-term activity measurements of mice showed that the developed activity measurement system is valid for its intended purpose. The assay of PGC-1 mRNA expression responses in human skeletal muscle confirmed that the alternative promoter originated transcripts are vastly upregulated after both EE and RE, whereas the proximal promoter originated transcripts are less inducible and were upregulated only after EE. Truncated PGC-1α transcripts were upregulated after both EE and RE. In conclusion, the current dissertation described the characteristics of inherited oxidative capacity in skeletal muscle and supported the significant role of aerobic metabolism in the development of metabolic diseases. Furthermore, HFD induces angiogenesis in skeletal muscle, which may be linked to increased expression of HIF-1α and VEGF-A in endothelial cells. The current dissertation supported the idea that PGC-1α isoforms may have an important role in exercise mode-specific muscle adaptations. The current results increase our knowledge of factors affecting the oxidative capacity of skeletal muscles, which may help to understand the pathogenic processes of physical inactivity-mediated disorders, as well as helping to develop new treatments or preventive therapies.

The dissertation is available for free:

https://jyx.jyu.fi/dspace/handle/123456789/48494

 

The More information, please contact with Mr. Mika Silvennoinen

mika.m.silvennoinen@jyu.fi

 

City (for University):
University of Jyväskylä