Background: Chronic fatigue syndrome has been shown in a study to have fast-twitch muscle fibers and cold sensitivity is a common complaint in patients with CFS. Mitochondrial biogenesis is dependant on a transcription protein that interacts with other proteins in mitochondrial synthesis. PGC-1a activity directly effects the number and density of mitochondria. Different tissues have different levels of mitochondria.
Other studies have shown that increasing the number of mitochondria may result in longer lifespan and improved quality of life. In mice, increasing the number of mitochondria can improve muscle weakness and increase survival. With more mitochondria, mice lived longer without symptoms.
"The essential role of PGC-1 in adaptive thermogenesis is convincingly demonstrated by the observation that the PGC-1-deficient mice are unable to withstand a cold stress (4°C) for longer than 6 h due to a continuous decrease of core body temperature. Wild-type control mice, on the other hand, were able to tolerate the cold stress by keeping their core body temperature at 36.5°C, after an initial drop of 1.5°C.".....
Pietrangelo explains from his study that "fibre-type proportion was significantly altered in CSF samples, which showed a shift from the slow- to the fast-twitch phenotype. Lane showed several years ago that patients with lactate responses to exercise also exhibited a lower proportion of mitochondrial-rich fiber type. Liang explains that "skeletal muscle fibers are classified into three types: type I, type IIa, and type IIb. Slow-twitch type I and fast-twitch type IIa fibers contain more mitochondria and exhibit relatively higher rates of oxidative metabolism. In contrast, type IIb fibers have fewer mitochondria and are metabolically glycolytic. It is now well established that PGC-1 induces a remodeling of skeletal muscle fiber composition. In general, the ratio of glycolytic type IIb fibers to the more oxidative type I and type IIa fibers decreases. The expression of PGC-1 in skeletal muscle is readily inducible by both short-term exercise and endurance training in rodent models and human subjects. Our understanding of the biological role of PGC-1 in skeletal muscle structure and function has been greatly improved through the use of gain of function and loss of function mouse models. In a gain of function transgenic model, PGC-1 is overexpressed in a skeletal muscle-specific manner under the control of the muscle creatine kinase (MCK) promoter. PGC-1 overexpression results in the conversion of fast-twitch type IIb muscle fibers to type IIa and slow-twitch type I fibers by 20% and 10%, respectively, in plantaris muscle." Handchin explains the mice with an absence of PGC-1a in muscle present with an increase inflammatory cytokines including Tnf-a and IL-6 and that heterozygous animals produce smaller but significant increases in these cytokines. This provides evidence that inflammation, he says, is originating from the muscles themselves. A drop in PGC-1a expression in heterozygoes is similar to that of patients with a 36% drop in PGC-1a in diabetic patients which also corresponds to a PGC-1a drop in active vs. non-active animals. He says also that while one can not make a causality connection between PGC-1a and pro-inflammatory genes is not possible in humans, the patients do exhibit an increase in Tnf-a and Il-6 in muscle and Il-6 in serum. The reduction of PGC-1a mRNA in diabetic Type 2 patients is likely linked to a chronic state of low-grade inflammation." (Handchin)
Ding shows that "Nrf2 suppression blocks myogenesis. The knockdown of Nrf2 by siRNA transfection blocked the expression of myogenin and MHC, as well as morphological changes in myotube formation. We also verified these results via MCK-dependent luciferase assay using the MCK-responsive luciferase reporter plasmid, MCK-Luc. The knockdown of Nrf2 reduced MCK promoter activity, when measured 48 hours after the induction of differentiation." He also demonstrated that H2O2 signals are important for signaling and induction of GSH and the GSH/GSSH during muscle differentiation via Nrf2/GCL/GR/GSH signal pathway.
I can not provide all the citation below as it is in Japanese or Chinese.
Liang, H. and Ward, W. F. (2008). Pgc-1: a key regulator of energy metabolism. http://www.citeulike.org/user/HEIRS/article/5805611
Ding, Y., Choi, K. J., Kim, J. H., Han, X., Piao, Y., Jeong, J.-H., Choe, W., Kang, I., Ha, J., Forman, H. J., Lee, J., Yoon, K.-S., and Kim, S. S. (2008). Endogenous hydrogen peroxide regulates glutathione redox via nuclear factor erythroid 2-related factor 2 downstream of phosphatidylinositol 3-kinase during muscle differentiation. Am J Pathol, 172(6):1529-1541. http://www.citeulike.org/user/HEIRS/article/3481324
New Hope For Treating Common Form Of Inherited Neuromuscular Disease. Medical News Today.
Lane, R. J., Barrett, M. C., Woodrow, D., Moss, J., Fletcher, R., and Archard, L. C. (1998). Muscle fibre characteristics and lactate responses to exercise in chronic fatigue syndrome. Journal of neurology, neurosurgery, and psychiatry, 64(3):362-367. http://www.citeulike.org/user/HEIRS/article/3578915
Pietrangelo, T., Toniolo, L., Paoli, A., Fulle, S., Puglielli, C., Fan X00f2, G., and Reggiani, C. (2009). Functional characterization of muscle fibres from patients with chronic fatigue syndrome: case-control study. International journal of immunopathology and pharmacology, 22(2):427-436. http://www.citeulike.org/user/HEIRS/article/4812216
Handschin, C. and Spiegelman, B. M. (2008). The role of exercise and pgc1alpha in inflammation and chronic disease. Nature, 454(7203):463-469. http://www.citeulike.org/user/HEIRS/article/3038457
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