Substrate utilisation of cultured skeletal muscle cells in patients with CFS

Cara Tomas,Mark Walker,Julia L Newton,Joanna L Elson

doi:10.1038/s41598-020-75406-w

Abstract

Chronic fatigue syndrome (CFS) patients often suffer from severe muscle pain and an inability to exercise due to muscle fatigue. It has previously been shown that CFS skeletal muscle cells have lower levels of ATP and have AMP-activated protein kinase dysfunction. This study outlines experiments looking at the utilisation of different substrates by skeletal muscle cells from CFS patients (n = 9) and healthy controls (n = 11) using extracellular flux analysis. Results show that CFS skeletal muscle cells are unable to utilise glucose to the same extent as healthy control cells. CFS skeletal muscle cells were shown to oxidise galactose and fatty acids normally, indicating that the bioenergetic dysfunction lies upstream of the TCA cycle. The dysfunction in glucose oxidation is similar to what has previously been shown in blood cells from CFS patients. The consistency of cellular bioenergetic dysfunction in different cell types supports the hypothesis that CFS is a systemic disease. The retention of bioenergetic defects in cultured cells indicates that there is a genetic or epigenetic component to the disease. This is the first study to use cells derived from skeletal muscle biopsies in CFS patients and healthy controls to look at cellular bioenergetic function in whole cells.

Highlights

Chronic fatigue syndrome (CFS) patients often suffer from severe muscle pain and an inability to exercise due to muscle fatigue
This study showed that was the impairment present at baseline levels, but CFS patient cells had significantly lower levels of oxidative phosphorylation pathway (OXPHOS) when the cells were pushed to their maximum using a cellular stressor
Having previously shown that CFS peripheral blood mononuclear cells (PBMCs) have impaired OXPHOS in response to glucose, this technique is used in this study to investigate the ability of CFS skeletal muscle cells, and age/sex matched healthy control cells, to utilise different fuel sources for cellular energy production

Summary

Introduction

Chronic fatigue syndrome (CFS) patients often suffer from severe muscle pain and an inability to exercise due to muscle fatigue. The retention of bioenergetic defects in cultured cells indicates that there is a genetic or epigenetic component to the disease This is the first study to use cells derived from skeletal muscle biopsies in CFS patients and healthy controls to look at cellular bioenergetic function in whole cells. Our group has previously used peripheral blood mononuclear cells (PBMCs) to show that CFS patient cells in the presence of glucose do not utilise the oxidative phosphorylation pathway (OXPHOS), known as mitochondrial respiration, to the same extent as healthy c ontrols[4]. Having previously shown that CFS PBMCs have impaired OXPHOS in response to glucose, this technique is used in this study to investigate the ability of CFS skeletal muscle cells, and age/sex matched healthy control cells, to utilise different fuel sources for cellular energy production. This study is the first to use CFS skeletal muscle cells to look at cellular bioenergetic function in whole cells

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Conclusion