SAT0062 Association of Obesity with Rheumatoid Arthritis: the Visceral/Subcutaneous FAT Ratio Affects Disease Activity, Resistance to Methotrexate Treatment and the Expression of FAS Gene in Peripheral Blood
Authors: T. Higuchi, A. Nakamura, M. Tanino, Y. Koyama
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Adipose tissue is well known to induce adipocytokines and inflammatory cytokines. Recently, it has been reported that obesity may associate with disease severity and with resistance to treatments in rheumatoid arthritis (RA). On the other hand, the differences in the biological characters of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) have been discussed. So far, the involvement of these adipose tissues on the pathogenic importance in RA has not been elucidated. <h3>Objectives</h3> To investigate the impact of obesity or distribution of body fat on disease activity, therapeutic response and gene expression profiles of peripheral blood in RA patients. <h3>Methods</h3> A cross sectional image at navel level by Computed tomography (CT) was used for measuring the area of VAT and SAT in 125 women with RA. Next, we analyzed the correlations between disease activity score (DAS) and body mass index (BMI), VAT, SAT, or VAT/SAT ratio (V/S ratio). The DAS was randomly sampled if the treatment of patients was sustained for at least three months. As 11 of the patients were started MTX treatment after newly diagnosed as RA, the differences in the backgrounds of patients including BMI, VAT, SAT or V/S ratio were investigated between good/moderate and no response group determined by EULAR response criteria. Moreover, in the 7 of these untreated patients, gene expression profiles of peripheral blood were analyzed with using Agilent whole human genome 60K (single-color procedure). <h3>Results</h3> The significant correlation of DAS was found only with V/S ratio (p&lt;0.01) or VAT (p&lt;0.05). BMI seemed to be less influential in increasing DAS as compare with these parameters. In terms of influence on the efficacy of MTX treatment, V/S ratio was found to be significantly high (p&lt;0.05) in the no response group. As a result of analyzing gene expression profiles, positive correlation was found with the tumor necrosis factor (TNF) α induced protein 1 (TNFIP1), and negative correlation was detected with the FAS genes. <h3>Conclusions</h3> It is known that adipose tissue is capable to secret inflammatory cytokines, such as TNF. On the other hand, VAT was reported to be functionally different from SAT. The inflammatory cells including macrophages are known to be more prevalent in VAT compared with SAT. Moreover, SAT is reported to be not exacerbating, even protective for insulin resistance. Therefore, apart from BMI, SAT or VAT, we also focused on V/S ratio. With regard to disease severity or resistance to treatment in RA, the positive correlation was found not with BMI but with VAT, especially with V/S ratio. By using DNA microarray analysis, we found strong positive correlation between V/S ratio and the expression of TNFAP1. Meanwhile, it is of particular interest that V/S ratio was negatively correlated with the expression of FAS genes in the peripheral blood of RA patients. These results may suggest a strong connection between distribution of body fat and disease severity or resistance to treatment in RA. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3980