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Cited by 209Fibromyalgia and Chronic Fatigue Syndrome ResearchLong-Term Effects of COVID-19Mitochondrial Function and Pathology

Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome

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Fluge, Øystein, Mella, Olav, Bruland, Ove, Risa, Kristin, Dyrstad, Sissel E., Alme, Kine, Rekeland, Ingrid G., Sapkota, Dipak +18 more·2016·JCI Insight
DOI 10.1172/jci.insight.89376PMC PMC5161229
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Abstract

Myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) is a debilitating disease of unknown etiology, with hallmark symptoms including postexertional malaise and poor recovery. Metabolic dysfunction is a plausible contributing factor. We hypothesized that changes in serum amino acids may disclose specific defects in energy metabolism in ME/CFS. Analysis in 200 ME/CFS patients and 102 healthy individuals showed a specific reduction of amino acids that fuel oxidative metabolism via the TCA cycle, mainly in female ME/CFS patients. Serum 3-methylhistidine, a marker of endogenous protein catabolism, was significantly increased in male patients. The amino acid pattern suggested functional impairment of pyruvate dehydrogenase (PDH), supported by increased mRNA expression of the inhibitory PDH kinases 1, 2, and 4; sirtuin 4; and PPARδ in peripheral blood mononuclear cells from both sexes. Myoblasts grown in presence of serum from patients with severe ME/CFS showed metabolic adaptations, including increased mitochondrial respiration and excessive lactate secretion. The amino acid changes could not be explained by symptom severity, disease duration, age, BMI, or physical activity level among patients. These findings are in agreement with the clinical disease presentation of ME/CFS, with inadequate ATP generation by oxidative phosphorylation and excessive lactate generation upon exertion.

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Authors
Fluge, Ø., Mella, O., Bruland, O., Risa, K., Dyrstad, S. E., Alme, K., Rekeland, I. G., Sapkota, D., Røsland, G. V., Fosså, A., Ktoridou-Valen, I., Lunde, S., Sørland, K., Lien, K., Herder, I., Thürmer, H., Gotaas, M. E., Baranowska, K. A., Bohnen, L. M. L. J., Schäfer, C., McCann, A., Sommerfelt, K., Helgeland, L., Ueland, P. M., Dahl, O., & Tronstad, K. J.
Affiliations
  • Haukeland University Hospital (NO)
  • University of Bergen (NO)
  • Oslo University Hospital (NO)
  • Telemark Hospital (NO)
  • St Olav's University Hospital (NO)
  • University Hospital of North Norway (NO)
  • Bevital (Norway) (NO)
  • Department of Pediatrics and
ORCID
Venue
JCI Insight
Publisher
American Society for Clinical Investigation
Published
2016-12-22
Volume
1
Issue
21
Pages
e89376-e89376
ISSN
2379-3708 (ISSN-L)
DOI
10.1172/jci.insight.89376
PMC
PMC5161229
OpenAlex
W2563536139
Cited by
209
References
5
Citations by year
2026: 28 · 2025: 27 · 2024: 13 · 2023: 15 · 2022: 23 · 2021: 19 · 2020: 30 · 2019: 21 · 2018: 19 · 2017: 14
FWCI
13.76
Type
journal article
Language
en
Open access
Locations
  • JCI Insight (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • ME Association
  • Kavlifondet
  • Norges Forskningsråd
  • Haukeland Universitetssjukehus
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
  • Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
pyruvate dehydrogenase, serum amino acids, 3-methylhistidine, protein degradation, TCA cycle, energy metabolism, PPARδ, peripheral blood mononuclear cells, myoblasts, mitochondrial respiration, lactate secretion, oxidative phosphorylation, sex differences

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