Poster Topical Area: Vitamins and Minerals

Location: Hall D

Poster Board Number: 471

P26-009 - Collagen-induced arthritis alters citric cycle and one-carbon metabolismin vivo

Sunday, Jun 10
8:00 AM – 6:00 PM

Background. Rheumatoid arthritis (RA) is a systemic autoimmune disease accompanying with abnormal metabolic activities with unclear etiology and pathogenesis. Citric acid cycle is a central pathway connecting many metabolic routes. One-carbon (1C) metabolism is essential for DNA synthesis and methylation. Previous studies indicated that FLS cells from RA synovium have altered citric cycle activity. The objective of the present study was to investigate citric cycle and 1C metabolic kinetics during inflammation in vivo. Designs. Collagen-induced arthritis (CIA), a commonly used animal model for humans with RA was induced in mice. Stable isotopic labeling experiments were performed in cell models as well as in vivo to trace the citric cycle and 1C metabolic fluxes during inflammation. Twenty-10-week-old male C57BL/6JNarl mice were housed individually under pathogen-free condition on a 12h day/night cycle and received AIN93M diet ad lib during the experimental period. Arthritis was induced by 2 emulsion injections with the chicken type II collagen and Mycobacterium butyricum at the age of 12- and 14- week. Mice were sacrificed at the age of 23-weeks during chronic inflammation. Results & Conclusions. CIA resulted in swollen joints to various degree and low hemoglobin (11% reduction in hemoglobin compared to controls, p=0.01). CIA modestly increased intake (p<0.1) but not change body weight at peak inflammation. No significant difference was observed in weight, intake or feeding efficiency during chronic inflammation while inflammation sustained. CIA significantly decreased glucose utilization for citric cycle but promoted de novo serine synthesis from glycolysis. Furthermore, CIA significantly altered plasma formate concentrations, as well as the formate metabolic fluxes derived from serine, glycine, and glucose utilization. CIA decreased thymidine synthesis but promoted purine synthesis derived from one carbon moieties in the bone marrow during chronic inflammation. Transmethylation fluxes were also changed. In summary, chronic systemic inflammation drastically perturbs the metabolic homeostasis in vivo. The elucidation of metabolic kinetics can give new insights on pathogenesis, clinical complications, and future metabolic therapy in humans suffering chronic inflammatory diseases.

Funding Source: Supported by MOST 104-2320-B005-010-MY3 (Chiang), NSC103-2320-B005-006-MY3 (Chiang) and the Ministry of Education Taiwan (ROC) under the ATU plan (Chiang)

CoAuthors: Yi-Ying Lin – National Chung Hsing Univ; Yu Hsuan Huang – National Chung Hsing Univ; Nga-Lai Sou – National Chung Hsing Univ

EnPei Chiang

National Chung Hsing Univ
Taichung, Taichung, Taiwan (Republic of China)