Golomb 2023 Sci Rep: Difference between revisions

Latest revision as of 17:30, 17 July 2023

Golomb BA, Sanchez Baez R, Schilling JM, Dhanani M, Fannon MJ, Berg BK, Miller BJ, Taub PR, Patel HH (2023) Mitochondrial impairment but not peripheral inflammation predicts greater Gulf War illness severity. https://doi.org/10.1038/s41598-023-35896-w

» Sci Rep 13:10739. PMID: 37438460 Open Access

Golomb Beatrice A, Sanchez Baez Roel, Schilling Jan M, Dhanani Mehul, Fannon McKenzie J, Berg Brinton K, Miller Bruce J, Taub Pam R, Patel Hemal H (2023) Sci Rep

Abstract: 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.

• Bioblast editor: Plangger M • O2k-Network Lab: US CA San Diego Patel HH

Labels: MiParea: Respiration Pathology: Other

Organism: Human Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue

Coupling state: LEAK, OXPHOS, ET Pathway: F, N, S, NS, ROX HRR: Oxygraph-2k

2023-07

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 |title=Golomb BA, Sanchez Baez R, Schilling JM, Dhanani M, Fannon MJ, Berg BK, Miller BJ, Taub PR, Patel HH (2023) Mitochondrial impairment but not peripheral inflammation predicts greater Gulf War illness severity. https://doi.org/10.1038/s41598-023-35896-w
 |info=Sci Rep 13:10739. [https://www.ncbi.nlm.nih.gov/pubmed/37438460 PMID: 37438460 Open Access]
-|authors=Golomb BA, Sanchez Baez R, Schilling JM, Dhanani M, Fannon MJ, Berg BK, Miller BJ, Taub PR, Patel HH
+|authors=Golomb Beatrice A, Sanchez Baez Roel, Schilling Jan M, Dhanani Mehul, Fannon McKenzie J, Berg Brinton K, Miller Bruce J, Taub Pam R, Patel Hemal H
 |year=2023
 |journal=Sci Rep
 |abstract=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.
 |editor=[[Plangger M]]
+|mipnetlab=US CA San Diego Patel HH
 }}
 {{Labeling
 |area=Respiration
+|diseases=Other
+|organism=Human
+|tissues=Skeletal muscle
+|preparations=Permeabilized tissue
 |couplingstates=LEAK, OXPHOS, ET
 |pathways=F, N, S, NS, ROX