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Article

Metabolomic Biomarker Candidates for Skeletal Muscle Loss in the Collagen-Induced Arthritis (CIA) Model

1
VA San Diego Healthcare System, Veteran Medical Research Foundation, San Diego, CA 92161, USA
2
Hospital de Clínicas de Porto Alegre, Serviço de Reumatologia, Laboratório de Doenças Autoimunes, Porto Alegre 90035-903, Brazil
3
Queen Elizabeth Hospital and National Institute for Health Research, Birmingham Biomedical Research Centre, University of Birmingham, Birmingham B15 2TT, UK
4
Universidade La Salle, Canoas 92010-000, Brazil
5
Universidade do Vale do Rio dos Sinos, São Leopoldo 93022-750, Brazil
*
Author to whom correspondence should be addressed.
Academic Editor: Michael Freeley
J. Pers. Med. 2021, 11(9), 837; https://doi.org/10.3390/jpm11090837
Received: 20 July 2021 / Revised: 10 August 2021 / Accepted: 16 August 2021 / Published: 26 August 2021
(This article belongs to the Special Issue Precision Medicine for Inflammatory and Autoimmune Diseases)
There is no consensus for diagnosis or treatment of RA muscle loss. We aimed to investigate metabolites in arthritic mice urine as biomarkers of muscle loss. DBA1/J mice comprised collagen-induced arthritis (CIA) and control (CO) groups. Urine samples were collected at 0, 18, 35, 45, 55, and 65 days of disease and subjected to nuclear magnetic resonance spectroscopy. Metabolites were identified using Chenomx and Birmingham Metabolite libraries. The statistical model used principal component analysis, partial least-squares discriminant analysis, and partial least-squares regression analysis. Linear regression and Fisher’s exact test via the MetaboAnalyst website were performed (VIP-score). Nearly 100 identified metabolites had CIA vs. CO and disease time-dependent differences (p < 0.05). Twenty-eight metabolites were muscle-associated: carnosine (VIPs 2.8 × 102) and succinyl acetone (VIPs 1.0 × 10) showed high importance in CIA vs. CO models at day 65; CIA pair analysis showed histidine (VIPs 1.2 × 102) days 55 vs. 65, histamine (VIPs 1.1 × 102) days 55 vs. 65, and L-methionine (VIPs 1.1 × 102) days 0 vs. 18. Carnosine was fatigue- (0.039) related, creatine was food intake- (−0.177) and body weight- (−0.039) related, and both metabolites were clinical score- (0.093; 0.050) and paw edema- (0.125; 0.026) related. Therefore, muscle metabolic alterations were detected in arthritic mice urine, enabling further validation in RA patient’s urine, targeting prognosis, diagnosis, and monitoring of RA-mediated muscle loss. View Full-Text
Keywords: rheumatoid arthritis; precision medicine; NMR; CIA; metabolomics; cachexia; biomarkers rheumatoid arthritis; precision medicine; NMR; CIA; metabolomics; cachexia; biomarkers
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MDPI and ACS Style

Alabarse, P.V.G.; Silva, J.M.S.; Santo, R.C.E.; Oliveira, M.S.; Almeida, A.S.; de Oliveira, M.S.; Immig, M.L.; Freitas, E.C.; Teixeira, V.O.N.; Bathurst, C.L.; Brenol, C.V.; Filippin, L.I.; Young, S.P.; Lora, P.S.; Xavier, R.M. Metabolomic Biomarker Candidates for Skeletal Muscle Loss in the Collagen-Induced Arthritis (CIA) Model. J. Pers. Med. 2021, 11, 837. https://doi.org/10.3390/jpm11090837

AMA Style

Alabarse PVG, Silva JMS, Santo RCE, Oliveira MS, Almeida AS, de Oliveira MS, Immig ML, Freitas EC, Teixeira VON, Bathurst CL, Brenol CV, Filippin LI, Young SP, Lora PS, Xavier RM. Metabolomic Biomarker Candidates for Skeletal Muscle Loss in the Collagen-Induced Arthritis (CIA) Model. Journal of Personalized Medicine. 2021; 11(9):837. https://doi.org/10.3390/jpm11090837

Chicago/Turabian Style

Alabarse, Paulo V. G., Jordana M. S. Silva, Rafaela C. E. Santo, Marianne S. Oliveira, Andrelise S. Almeida, Mayara S. de Oliveira, Mônica L. Immig, Eduarda C. Freitas, Vivian O. N. Teixeira, Camilla L. Bathurst, Claiton V. Brenol, Lidiane I. Filippin, Stephen P. Young, Priscila S. Lora, and Ricardo M. Xavier. 2021. "Metabolomic Biomarker Candidates for Skeletal Muscle Loss in the Collagen-Induced Arthritis (CIA) Model" Journal of Personalized Medicine 11, no. 9: 837. https://doi.org/10.3390/jpm11090837

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