Abstract: "Assessment of Cellular Bioenergetics in CFS" (Newton team, Newcastle, UK)

[Tom Kindlon]

Poster presentation, IACFS/ME 2016 conference

Assessment of Cellular Bioenergetics in Chronic Fatigue Syndrome

Cara Tomas, Julia Newton, Audrey Brown, Gina Rutherford, Philip Manning
Newcastle University, UK

Introduction:

Abnormalities in bioenergetic function have been cited as one possible cause for chronic fatigue syndrome (CFS). One hypothesis to explain this suggests that CFS may be caused, at least in part, by an acquired mitochondrial dysfunction.

Extracellular flux analysers make real-time, in vitro assessment of cellular energy pathways possible. Using this technology, mitochondrial function can be measured in a variety of cell types in real-time thus increasing our understanding of the role of metabolism in CFS.

Objectives:

This project aims to utilise extracellular flux detection technology in order to investigate the cellular bioenergetics of different cell types obtained from CFS patients and healthy controls.

Methods:

Mitochondrial stress tests were conducted using skeletal muscle cells and peripheral blood mononuclear cells (PBMCs) derived from CFS patients and controls. During this test mitochondrial complexes are inhibited in turn to modulate respiration so mitochondrial function can be evaluated. The oxygen consumption rate of cells is measured which allows keys parameters of mitochondrial function to be measured and calculated in a single experiment, providing an overall assessment of mitochondrial function. Parameters measured are: basal respiration, maximal respiration and non-mitochondrial respiration. Proton leak, ATP-production and spare respiratory capacity are subsequently able to be calculated using the three measured parameters.

CFS patients whose samples were used in these studies were diagnosed using the Fukuda definition.

Results:

Results using skeletal muscle cells obtained from CFS patients (n=3) and controls (n=5), indicate that there is no difference in the energy profiles of the skeletal muscle cells of CFS patients in any of the parameters investigated.

Mitochondrial stress test results using PBMCs show CFS PBMCs (n=7) to be significantly lower than control cells (n=10) in all parameters investigated (p≤0.016). Importantly, these results suggest that CFS PBMCs perform closer to their maximum under normal conditions. This means that when CFS PBMCs come under stress they are less able to increase their respiration rate to compensate for the increase in stress.

Conclusions:

These findings provide an interesting starting point for investigations into cellular bioenergetics in CFS.

Cara Jasmine Tomas; First year medical science PhD student; Institute of Cellular Medicine, Level 1, William Leech Building, Medical School, Newcastle University, Newcastle Upon-Tyne, NE2 4HH, England; c.j.tomas@ncl.ac.uk
This work was funded by the Medical Research Council and Newcastle University.

https://twitter.com/i/web/status/797129112653627392

 

[Valentijn]

It's great to see Newton on a more productive track again

 

[Mary]

Mitochondrial stress test results using PBMCs show CFS PBMCs (n=7) to be significantly lower than control cells (n=10) in all parameters investigated (p≤0.016). Importantly, these results suggest that CFS PBMCs perform closer to their maximum under normal conditions. This means that when CFS PBMCs come under stress they are less able to increase their respiration rate to compensate for the increase in stress.

I wonder if this has any correlation to the theory that people with ME/CFS are very often in a state of anaerobic metabolism, while doing very minimal effort, as opposed to the much more efficient aerobic metabolism. I think anaerobic metabolism is typically only used under stressful or strenuous circumstances, by ordinary healthy people.

 

[Jonathan Edwards]

This is an interesting finding. I wonder, however, why PBMC are studied. PBMC are a mixture of T and B lymphocytes, NK cells and monocytes. In general in the blood they are not expected to do anything at all. They are just 'in the post' to some tissue where they might function. Lymphocytes in blood have hardly any cytoplasm - just a thin ring you can hardly see - because they have no work to do. Monocytes have a bit more but increase their cytoplasm about tenfold when they get into tissue.

If you put B cells into tissue culture they almost all die rapidly. They are programmed to die anywhere where there are no VCAM-1 expressing 'nurse cells'. T cells hang around but do not do much unless you feed them an antigen. Monocytes turn into macrophages and start trying to eat the plastic with the result they spread out flat. I am not quite sure what this odd mix of cells is going to tell us.

In tissue culture more or less all the signals present in an acquired (i.e. not genetically programmed) disease are likely to be washed away. So any difference found in culture seems likely to be due either to genetics, or due to some sort of sampling bias due to the cells circulating being skewed in type or age before you start. A genetic difference would be interesting but I cannot see how it can be related to fatigue directly since people with ME are not born fatigued.

So I am not sure quite how one would interpret these findings. It seems worthwhile trying to study mitochondrial function but I am unsure this sort of approach will show anything up that we can make sense of.