Transcription Profile Analysis of Vastus Lateralis Muscle from Patients with Chronic Fatigue Syndrome, 2009, Pietrangelo et al.

[SNT Gatchaman]

Transcription Profile Analysis of Vastus Lateralis Muscle from Patients with Chronic Fatigue Syndrome
T. Pietrangelo; R. Mancinelli; L. Toniolo; G. Montanari; J. Vecchiet; G. Fanò; S. Fulle

Chronic fatigue syndrome (CFS) is a disabling condition characterized by unexplained chronic fatigue that impairs normal activities. Many body systems are affected and etiology has not yet been identified. In addition to immunological and psychological aspects, skeletal muscle symptoms are prominent in CFS patients.

In an effort to establish which pathways might be involved in the onset and development of muscle symptoms, we used global transcriptome analysis to identify genes that were differentially expressed in vastus lateralis muscle of female and male CFS patients. We found that the expression of genes that play key roles in mitochondrial function and oxidative balance, including superoxide dismutase 2, were altered, as were genes involved in energy production, muscular trophism and fiber phenotype determination. Importantly, the expression of a gene encoding a component of the nicotinic cholinergic receptor binding site was reduced, suggesting impaired neuromuscular transmission.

We argue that these major biological processes could be involved in and/or responsible for the muscle symptoms of CFS.

Link | PDF (International Journal of Immunopathology and Pharmacology) [Open Access]

 

[SNT Gatchaman]

This is one of the Italian ME/CFS muscle biopsy and follow-on papers. Given findings in Muscle abnormalities worsen after post-exertional malaise in long COVID (2024, Nature Communications) and their planned follow-on in ME/CFS, I thought it was good to have this paper in view.

 

[SNT Gatchaman]

They used Fukuda/CDC 94 criteria with small, equal numbers of male and female patients, with HCs.

Some quotes from introduction and methods —

CFS patients have been shown to have reduced serum concentrations of acylcamitine, probably reflecting a reduction in muscle mitochondrial energy production. Mild exercise produces substantial muscular acidification and muscle adenylate and creatine kinase activities are defective in the muscles of CFS patients (5). Moreover, muscle pain in the absence of peripheral tissue damage and reduced oxygen saturation after exercise have been reported (6).

In a previous study we demonstrated that oxidative damage in CFS altered fluidity and fatty acid composition of skeletal muscle membranes with a specific and peculiar pattern completely different from that obtained by patients suffering from fibromyalgia syndrome.

 

[SNT Gatchaman]

DEGs in both female and both male patients —

Upregulated

• POLB
• VLDLR

Downregulated

• SOD2
• FDXl
• NQOl
• PFKFB3
• PDK4
• ABCA5
• AMPD3
• CHRNAl
• MYF6
• CALMl
• TIEG

 

[SNT Gatchaman]

Some quotes from results section —

One characteristic of the CFS vastus lateralis gene profile was the depressed transcription of several genes implicated inthe energy metabolism o fskeletal muscle fibers. Specifically,we found that two allosteric enzymes, 6-phosphofructo2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and 6-phosphofructo-2-kinase/fructose-2,6biphosphatase I (PFKFB3), were down-regulated, suggesting that glycolysis and/or gluconeogenesis was impaired. In fact, this allosteric enzyme is bifunctional and its specific activity depends on posttrascriptional phosphorylation. Also downregulated was the gene for pyruvate dehydrogenase kinase, isoenzyme 4 (PDK4), which phosphorylates pyruvate dehydrogenase

Only one gene of possible relevance for energy balance, very low density lipoprotein receptor (VLDLR), was found to be up-regulated in both female and male patients. This gene encodes the receptor responsible for VLDL uptake into the fiber and is involved in the primary pathway of fatty acid transport in skeletal muscle

Many genes involved in focal adhesion control and cytoskeletal and/or extracellular matrix regulation were also found to be down-regulated in CFS patients. Among these were i) proline/argininerich end leucine-rich repeat protein (PRELP), encoding a protein linking type-I collagen to heparan sulfate basal membranes (19), collagen type-V alpha 3 (COL5A3), ii) LIM domain kinase 1 (LIMKl), encoding aprotein that links proteins involved in actin cytoskeleton organization (20), and iii) spermidine/ spermine Nl-acetyltransferase-l (SATl)

The gene, CHRNA1, encoding a component o the acetylcholine binding site of the nicotinic receptor (cholinergic receptor, nicotin, alpha polypeptide 1 [muscle]), was found to be down-regulated. The absence of this gene's product might imply an impaired ability to respond to motor neuron firing at the neuromuscular junction. Motor neuron firing is important for slow fiber-type specification (24).

The transcription factor, myogenic factor 6 (MYF6/MRF4/herculin), was found to be down-regulated in CFS patients. In the mouse, MFR4 accumulates in slow fibers, and there is evidence indicating that MFR4 regulates the shift of fiber type towards the slow phenotype (25). This suggests that muscle remodeling is directed towards the fast phenotype in CFS patients, an interpretation that is consistent with results from fiber typing at the protein level (7).

In Muscle abnormalities worsen after post-exertional malaise in long COVID (2024, Nature Communications) —

Patients with long COVID displayed a markedly lower exercise capacity, which related to skeletal muscle metabolic alterations and a shift towards more fast-fatigable fibers.

 

[Turtle]

This is one of the Italian ME/CFS muscle biopsy and follow-on papers. Given findings in Muscle abnormalities worsen after post-exertional malaise in long COVID (2024, Nature Communications) and their planned follow-on in ME/CFS, I thought it was good to have this paper in view.

Good thinking!
Thanks a lot for all of your posts. Your highlights and comments are really helpful and highly appreciated. Sometimes, being a poor alpha, you can make even me understand a bit of the science behind ME/CFS.
I found a connection with muscle changes in space. Maybe of interest to you. If not feel free to delete.
Schenkman 2016 'From slow to fast: hypogravity-induced remodeling of muscle fiber myosin phenotype'.

 

[SNT Gatchaman]

Thank you @Turtle - I've downloaded and will read.

 

[Turtle]

In Muscle abnormalities worsen after post-exertional malaise in long COVID (2024, Nature Communications) —[/QUOTE]

Appelmans.. Wüst mention that fibre-type shifts occur at a very slow pace. Discussion 2nd paragraph.

When rodents, having been in space, change muscles from slow to fast in just 7 days (even 4 is mentioned) could the pace of fibre-type shifts occur in a much faster pace in ME/CFS and LC?

From having lived with an avid time-trial cyclist, I remember that training a slow muscle into a fast muscle is incredibly difficult.

My first attempt at cycling after I got ME/CFS, a one meter high bridge halted me completely, after just having done 400 meters.
I was only bedridden for 3 days due to high fever. Not decondioned otherwise. The bike ride was just 2 months later.
I'm the pyknic type so I already must have had more fast muscles anyway.

Could hypoxia fast-track the muscle fibre shift?

 

[Turtle]

Low AT, no Krebscycle on exertion, lipids problematic, greater use of amino-acids lead to an environment better suited for fast muscles?

 

[Turtle]

Low AT, no Krebscycle on exertion, lipids problematic, greater use of amino-acids lead to an environment better suited for fast muscles?

@SNT Gatchaman. Perish or adapt?