Altered Fatty Acid Oxidation in Lymphocyte Populations of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

• Published in: International journal of molecular sciences Vol. 24; no. 3; p. 2010
• Main Authors: Maya, Jessica, Leddy, Sabrina M, Gottschalk, C Gunnar, Peterson, Daniel L, Hanson, Maureen R
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 19.01.2023; MDPI
• Subjects: Antigens; beta-oxidation; CD4 antigen; CD4-Positive T-Lymphocytes; CD8 antigen; CD8-Positive T-Lymphocytes; Cell activation; Cells; Chronic fatigue syndrome; Cytokines; Dehydrogenases; Effector cells; Encephalomyelitis; Enzymes; Fatigue; Fatigue Syndrome, Chronic - immunology; fatty acid oxidation; Fatty acids; Fatty Acids - immunology; Humans; Illnesses; Immune system; Inflammation; Killer Cells, Natural; Lipid metabolism; Lipid Metabolism - immunology; Lipids; Lymphocyte Subsets - immunology; Lymphocytes; Lymphocytes - immunology; Lymphocytes T; Memory; Memory cells; Metabolic pathways; Metabolism; Metabolites; myalgic encephalomyelitis; Natural Killer cells; Oxidation; Oxidation-Reduction; Phosphorylation; Populations; Respiration; Signs and symptoms; T cells; Natural Killer cells; beta-oxidation; immunometabolism; chronic fatigue syndrome; fatty acid oxidation; myalgic encephalomyelitis; T cells
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24032010

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disabling multisystem illness in which individuals are plagued with fatigue, inflammatory symptoms, cognitive dysfunction, and the hallmark symptom, post-exertional malaise. While the cause of this disease remains unknown, there is evidence of a potential infectious component that, along with patient symptoms and common onsets of the disease, implicates immune system dysfunction. To further our understanding of the state of ME/CFS lymphocytes, we characterized the role of fatty acids in isolated Natural Killer cells, CD4+ T cells, and CD8+ T cells in circulation and after overnight stimulation, through implicit perturbations to fatty acid oxidation. We examined samples obtained from at least 8 and as many as 20 subjects for immune cell fatty acid characterization in a variety of experiments and found that all three isolated cell types increased their utilization of lipids and levels of pertinent proteins involved in this metabolic pathway in ME/CFS samples, particularly during higher energy demands and activation. In T cells, we characterized the cell populations contributing to these metabolic shifts, which included CD4+ memory cells, CD4+ effector cells, CD8+ naïve cells, and CD8+ memory cells. We also discovered that patients with ME/CFS and healthy control samples had significant correlations between measurements of CD4+ T cell fatty acid metabolism and demographic data. These findings provide support for metabolic dysfunction in ME/CFS immune cells. We further hypothesize about the consequences that these altered fuel dependencies may have on T and NK cell effector function, which may shed light on the illness's mechanism of action.