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A map of metabolic phenotypes in patients with myalgic encephalomyelitis/chronic fatigue syndrome
Fredrik Hoel, … , Øystein Fluge, Karl J. Tronstad
Fredrik Hoel, … , Øystein Fluge, Karl J. Tronstad
Published August 23, 2021
Citation Information: JCI Insight. 2021;6(16):e149217. https://doi.org/10.1172/jci.insight.149217.
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Research Article Immunology Metabolism

A map of metabolic phenotypes in patients with myalgic encephalomyelitis/chronic fatigue syndrome

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Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease usually presenting after infection. Emerging evidence supports that energy metabolism is affected in ME/CFS, but a unifying metabolic phenotype has not been firmly established. We performed global metabolomics, lipidomics, and hormone measurements, and we used exploratory data analyses to compare serum from 83 patients with ME/CFS and 35 healthy controls. Some changes were common in the patient group, and these were compatible with effects of elevated energy strain and altered utilization of fatty acids and amino acids as catabolic fuels. In addition, a set of heterogeneous effects reflected specific changes in 3 subsets of patients, and 2 of these expressed characteristic contexts of deregulated energy metabolism. The biological relevance of these metabolic phenotypes (metabotypes) was supported by clinical data and independent blood analyses. In summary, we report a map of common and context-dependent metabolic changes in ME/CFS, and some of them presented possible associations with clinical patient profiles. We suggest that elevated energy strain may result from exertion-triggered tissue hypoxia and lead to systemic metabolic adaptation and compensation. Through various mechanisms, such metabolic dysfunction represents a likely mediator of key symptoms in ME/CFS and possibly a target for supportive intervention.

Authors

Fredrik Hoel, August Hoel, Ina K.N. Pettersen, Ingrid G. Rekeland, Kristin Risa, Kine Alme, Kari Sørland, Alexander Fosså, Katarina Lien, Ingrid Herder, Hanne L. Thürmer, Merete E. Gotaas, Christoph Schäfer, Rolf K. Berge, Kristian Sommerfelt, Hans-Peter Marti, Olav Dahl, Olav Mella, Øystein Fluge, Karl J. Tronstad

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Figure 5

Key characteristics of ME/CFS metabotypes.

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Key characteristics of ME/CFS metabotypes.
Key serum molecules were inve...
Key serum molecules were investigated to evaluate contextual changes in systemic energy metabolism. (A and B) Nonesterified saturated fatty acids (A) and saturated acylcarnitines (B) in the ME/CFS group (ME) and subsets (M1-M3), calculated relative to the HC group. The fatty acid chain length is denoted on the x axis (Carbons#). (C–H) Serum levels of pyruvate (glucose metabolite) (C), glycerol (product of lipolysis) (D), kynurenate (Trp metabolite) (E), xanthosine (purine metabolite) (F), 3-hydroxybutyrate (β-hydroxybutyrate; ketone body) (G), and isovalerylglycine (BCAA product) (H). The metabolite levels are displayed as log2 transformed normalized compound peak values. Data are presented as mean ± SD. *P < 0.05, 2-tailed Welch’s test; **q <0.05, adjusted P value.

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ISSN 2379-3708

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