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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 6

Overview of lipid classes.

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Overview of lipid classes.
The serum lipidome data set was analyzed to o...
The serum lipidome data set was analyzed to overall compare the ME/CFS group (ME/All) and the 3 metabotype subsets (M1–M3) relative to the HC group. (A) The volcano plots give a general overview of all lipid molecules in a given class, with the –log10 of the P value on the y axis and log2 fold change on the x axis. Each dot represents a metabolite and is colored according to direction of change and significance level relative to HC as indicated (P < 0.05, 2-tailed Welch’s test; q < 0.05, adjusted P value). The number in each quadrant provides the respective counts of q-significant metabolites, and additional p-significant metabolites are shown in parentheses. (B) The relative amount of specific fatty acids (FA, first column) in the different lipid classes (column title) in the total ME/CFS group (bottom label, A) and according to metabotype subsets (M1–M3). The color of the heatmap cells display the log2 fold change relative to HC, as indicated. *P < 0.05, 2-tailed Welch’s test; **q < 0.05, adjusted P value. Total, total sum of fatty acids across all lipid classes; CE, cholesterol ester; CER, ceramide; DAG, diacylglycerol; DCER, dihydroceramide; FFA, free fatty acid (synonymous to nonesterified fatty acid, NEFA); HCER, hexosylceramide; LCER, lactosylceramide; LPC, lysophosphatidylcholine; LPE, lysophosphatidylethanolamine; LPL, lysophospholipid; MAG, monoacylglycerol; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PI, phosphatidylinositol; PL, phospholipids, SM, sphingomyelin; SP, sphingolipids; TAG, triacylglycerol.

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