Metabolism in Chronic Fatigue Syndrome

Armstrong, Christopher W.; McGregor, Neil; Butt, Henry L.; Gooley, Paul R.

doi:10.1016/b978-0-12-801401-1.00005-0

Cited by 55 publications

(42 citation statements)

References 202 publications

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“…Our unpublished results and along with the other data from different organ systems including skeletal muscles during HHcy condition, may point to the compromised oxidative stress handling during HHcy condition [8, 45]. Further, oxidative stress has been implicated with fatigue, mitochondrial dysfunction as well [46]. When considered moderate exercise and HHcy both increase oxidative stress [8, 47], it is still not clear how HHcy condition differs from exercise.…”

Section: Discussionmentioning

confidence: 80%

Hyperhomocysteinemia associated skeletal muscle weakness involves mitochondrial dysfunction and epigenetic modifications

Veeranki

Winchester

Tyagi

2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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HHcy has been implicated in elderly frailty, but the underlying mechanisms are poorly understood. Using C57 and CBS+/- mice and C2C12 cell line, we investigated mechanisms behind HHcy induced skeletal muscle weakness and fatigability. Possible alterations in metabolic capacity (levels of LDH, CS, MM-CK and COX-IV), in structural proteins (levels of dystrophin) and in mitochondrial function (ATP production) were examined. An exercise regimen was employed to reverse HHcy induced changes. CBS+/- mice exhibited more fatigability, and generated less contraction force. No significant changes in muscle morphology were observed. However, there is corresponding reduction in large muscle fiber number in CBS+/- mice. Excess fatigability was not due to changes in key enzymes involved in metabolism, but was due to reduced ATP levels. A marginal reduction in dystrophin levels along with a decrease in mitochondrial transcription factor A (mtTFA) were observed. There was also an increase in the mir-31, and mir-494 quantities that were implicated in dystrophin and mtTFA regulation respectively. The molecular changes elevated during HHcy, with the exception of dystrophin levels, were reversed after exercise. In addition, amount of NRF-1, one of the transcriptional regulators of mtTFA, was significantly decreased. Furthermore, there was enhancement in mir-494 levels and a concomitant decline in mtTFA protein quantity in homocysteine treated cells. These changes in C2C12 cells were also accompanied by an increase in DNMT3a and DNMT3b proteins and global DNA methylation levels. Together, these results suggest that HHcy plays a causal role in enhanced fatigability through mitochondrial dysfunction which involves epigenetic changes.

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Section: Discussionmentioning

confidence: 80%

Hyperhomocysteinemia associated skeletal muscle weakness involves mitochondrial dysfunction and epigenetic modifications

Veeranki

Winchester

Tyagi

2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…Given the symptoms of fatigue and postexertional malaise, there has also been substantial research into metabolism in patients with ME/CFS. Studies have shown some evidence of oxidative stress and decreased coenzyme Q10 in ME/CFS (19)(20)(21)(22). The findings are conflicting with regard to ME/CFS cellular mitochondrial content, but multiple studies have found no difference in specific mitochondrial complex activities (19,(23)(24)(25).…”

Section: Resultsmentioning

confidence: 99%

Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations

Mandarano¹,

Maya²,

Giloteaux³

et al. 2020

Journal of Clinical Investigation

125

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“…ME/CFS has been found to involve irregularities in metabolism, energy, amino acids, nucleotides, nitrogen, hormones, and oxidative stress (Armstrong et al, 2014;Germain et al, 2017). In particular, it has been proposed that the severe and prolonged fatigue experienced by ME/CFS patients may be a consequence of abnormalities in bioenergetic function (Tomas et al, 2017).…”

Section: Metabolic Irregularitiesmentioning

confidence: 99%

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome—Metabolic Disease or Disturbed Homeostasis due to Focal Inflammation in the Hypothalamus?

Hatziagelaki

Adamaki

Tsilioni

et al. 2018

J Pharmacol Exp Ther

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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex disease characterized by debilitating fatigue, lasting for at least 6 months, with associated malaise, headaches, sleep disturbance, and cognitive impairment, which severely impacts quality of life. A significant percentage of ME/CFS patients remain undiagnosed, mainly due to the complexity of the disease and the lack of reliable objective biomarkers. ME/CFS patients display decreased metabolism and the severity of symptoms appears to be directly correlated to the degree of metabolic reduction that may be unique to each individual patient. However, the precise pathogenesis is still unknown, preventing the development of effective treatments. The ME/CFS phenotype has been associated with abnormalities in energy metabolism, which are apparently due to mitochondrial dysfunction in the absence of mitochondrial diseases, resulting in reduced oxidative metabolism. Such mitochondria may be further contributing to the ME/CFS symptomatology by extracellular secretion of mitochondrial DNA, which could act as an innate pathogen and create an autoinflammatory state in the hypothalamus. We propose that stimulation of hypothalamic mast cells by environmental, neuroimmune, pathogenic and stress triggers activates microglia, leading to focal inflammation in the brain and disturbed homeostasis. This process could be targeted for the development of novel effective treatments.

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Metabolism in Chronic Fatigue Syndrome

Cited by 55 publications

References 202 publications

Hyperhomocysteinemia associated skeletal muscle weakness involves mitochondrial dysfunction and epigenetic modifications

Hyperhomocysteinemia associated skeletal muscle weakness involves mitochondrial dysfunction and epigenetic modifications

Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome—Metabolic Disease or Disturbed Homeostasis due to Focal Inflammation in the Hypothalamus?

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