Altered lipid metabolism in synovial fibroblasts of individuals at risk of developing rheumatoid arthritis

Fibroblast-like synoviocytes (FLS) can augment the inflammatory process observed in synovium of patients with rheumatoid arthritis (RA). A recent transcriptomic study in synovial biopsies revealed changes in metabolic pathways before disease onset in absence of synovial tissue inflammation. This raises the question whether alterations in cellular metabolism in tissue resident FLS underlie disease pathogenesis. To study this, we compared the metabolic profile of FLS isolated from synovial biopsies from individuals with arthralgia who were autoantibody positive but without any evidence of arthritis (RA-risk individuals, n = 6) with FLS from patients with RA (n = 6), osteoarthritis (OA, n = 6) and seronegative controls (n = 6). After synovial digestion, FLS were cultured in vitro and cellular metabolism was assessed using quantitative PCR, flow cytometry, XFe96 Seahorse Analyzer and tritium-labelled oleate oxidation assays. Real-time metabolic profiling revealed that basal (p