Mitochondrial impairment but not peripheral inflammation predicts greater Gulf War illness severity.

Autor:	Golomb BA; Department of Medicine, University of California, San Diego, 9500 Gilman Drive #0995, La Jolla, CA, 92093-0995, USA. bgolomb@ucsd.edu., Sanchez Baez R; Department of Medicine, University of California, San Diego, 9500 Gilman Drive #0995, La Jolla, CA, 92093-0995, USA.; San Ysidro Health Center, San Diego, CA, 92114, USA., Schilling JM; VA San Diego Healthcare System and Department of Anesthesiology, University of California, San Diego, San Diego, CA, 92161, USA., Dhanani M; VA San Diego Healthcare System and Department of Anesthesiology, University of California, San Diego, San Diego, CA, 92161, USA.; Avidity Biosciences, San Diego, CA, 92121, USA., Fannon MJ; VA San Diego Healthcare System and Department of Anesthesiology, University of California, San Diego, San Diego, CA, 92161, USA., Berg BK; Department of Medicine, University of California, San Diego, 9500 Gilman Drive #0995, La Jolla, CA, 92093-0995, USA., Miller BJ; Department of Medicine, University of California, San Diego, 9500 Gilman Drive #0995, La Jolla, CA, 92093-0995, USA., Taub PR; Division of Cardiovascular Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA, 92037, USA., Patel HH; VA San Diego Healthcare System and Department of Anesthesiology, University of California, San Diego, San Diego, CA, 92161, USA.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2023 Jul 12; Vol. 13 (1), pp. 10739. Date of Electronic Publication: 2023 Jul 12.
DOI:	10.1038/s41598-023-35896-w
Abstrakt:	Gulf War illness (GWI) is an important exemplar of environmentally-triggered chronic multisymptom illness, and a potential model for accelerated aging. Inflammation is the main hypothesized mechanism for GWI, with mitochondrial impairment also proposed. No study has directly assessed mitochondrial respiratory chain function (MRCF) on muscle biopsy in veterans with GWI (VGWI). We recruited 42 participants, half VGWI, with biopsy material successfully secured in 36. Impaired MRCF indexed by complex I and II oxidative phosphorylation with glucose as a fuel source (CI&CIIOXPHOS) related significantly or borderline significantly in the predicted direction to 17 of 20 symptoms in the combined sample. Lower CI&CIIOXPHOS significantly predicted GWI severity in the combined sample and in VGWI separately, with or without adjustment for hsCRP. Higher-hsCRP (peripheral inflammation) related strongly to lower-MRCF (particularly fatty acid oxidation (FAO) indices) in VGWI, but not in controls. Despite this, whereas greater MRCF-impairment predicted greater GWI symptoms and severity, greater inflammation did not. Surprisingly, adjusted for MRCF, higher hsCRP significantly predicted lesser symptom severity in VGWI selectively. Findings comport with a hypothesis in which the increased inflammation observed in GWI is driven by FAO-defect-induced mitochondrial apoptosis. In conclusion, impaired mitochondrial function-but not peripheral inflammation-predicts greater GWI symptoms and severity. (© 2023. The Author(s).)
Databáze:	MEDLINE
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