Metabolic disturbances associated with systemic lupus erythematosus

Tianfu Wu, Chun Xie, Jie Han, Yujin Ye, Jim Weiel, Quan Li, Irene Blanco, Chul Ahn, Nancy Olsen, Chaim Putterman, Ramesh Saxena, Chandra Mohan

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

The metabolic disturbances that underlie systemic lupus erythematosus are currently unknown. A metabolomic study was executed, comparing the sera of 20 SLE patients against that of healthy controls, using LC/MS and GC/MS platforms. Validation of key differences was performed using an independent cohort of 38 SLE patients and orthogonal assays. SLE sera showed evidence of profoundly dampened glycolysis, Krebs cycle, fatty acid β oxidation and amino acid metabolism, alluding to reduced energy biogenesis from all sources. Whereas long-chain fatty acids, including the n3 and n6 essential fatty acids, were significantly reduced, medium chain fatty acids and serum free fatty acids were elevated. The SLE metabolome exhibited profound lipid peroxidation, reflective of oxidative damage. Deficiencies were noted in the cellular anti-oxidant, glutathione, and all methyl group donors, including cysteine, methionine, and choline, as well as phosphocholines. The best discriminators of SLE included elevated lipid peroxidation products, MDA, gamma-glutamyl peptides, GGT, leukotriene B4 and 5-HETE. Importantly, similar elevations were not observed in another chronic inflammatory autoimmune disease, rheumatoid arthritis. To sum, comprehensive profiling of the SLE metabolome reveals evidence of heightened oxidative stress, inflammation, reduced energy generation, altered lipid profiles and a pro-thrombotic state. Resetting the SLE metabolome, either by targeting selected molecules or by supplementing the diet with essential fatty acids, vitamins and methyl group donors offers novel opportunities for disease modulation in this disabling systemic autoimmune ailment.

Original languageEnglish (US)
Article numbere37210
JournalPloS one
Volume7
Issue number6
DOIs
StatePublished - Jun 19 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Wu, T., Xie, C., Han, J., Ye, Y., Weiel, J., Li, Q., Blanco, I., Ahn, C., Olsen, N., Putterman, C., Saxena, R., & Mohan, C. (2012). Metabolic disturbances associated with systemic lupus erythematosus. PloS one, 7(6), [e37210]. https://doi.org/10.1371/journal.pone.0037210