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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 3

Validation of different metabotypes.

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Validation of different metabotypes.
Metabolomics in serum from 35 healt...
Metabolomics in serum from 35 healthy controls (HC) and 83 patients with ME/CFS (ME) identified 159 significantly different metabolites (2-tailed Welch’s test, P < 0.05). (A) Principal component analysis (PCA) plot based on the significantly different metabolites. The PCA was performed independently of the introductory k-means clustering analysis. However, the clusters from the k-means analysis (in Figure 2C) have been used as an overlay to evaluate the associations and robustness of the proposed ME/CFS subsets. The sex of each subject is also indicated (dots, female; triangles, male). (B) Loading plot showing the contributions of the 30 main metabolites of PC1 and PC2, color-coded according to the metabolite class. (C–E) Clinical laboratory measurements of serum glucose (C), serum triglycerides (s-TAG) (D), and serum nonesterified fatty acids (s-NEFA) (E). Data are presented as mean ± SD, and the reference range is shown with dotted lines. (F) Mean steps/24 hours. P values; 1-way Welch’s ANOVA test, comparison of M1, M2, and M3. *P < 0.05; ****P < 0.00001; 2-tailed Welch’s test.

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ISSN 2379-3708

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