FRI0105 EXPRESSION OF UNCOUPLING PROTEIN-1 IN SUBCUTANEOUS FAT IS INCREASED BY TOCILIZUMAB
Authors: Lovisa Lyngfelt, Malin C. Erlandsson, Karin Me Andersson, Sofia Töyrä Silfverswärd, Maria I Bokarewa
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Adipose tissue is an important player in cardiovascular (CV) morbidity. Thermogenic brown adipocytes, rich with uncoupling protein 1 (UCP1), increase metabolic and CV health. (1) <h3>Objectives:</h3> Study the impact of anti-rheumatic treatment on production of UCP1 in subcutaneous fat of RA patients. <h3>Methods:</h3> Samples of subcutaneous fat were collected from 125 female RA patients by aspiration from periumbilical region. Expression of UCP1 and a reverse cholesterol transport protein ABCA1 were measured by qPCR and analysied with respect to anti-rheumatic treatment and clinical disease activity. Bt treatment, the patient comprised 4 major groups including tocilizumab (Toci, n=14), anti-TNF (n=29), methotrexate monotherapy (n=47) and methotrexate-sulfasalazine-hyroxychloroquine (tripple therapy, n=15). CV risk was estimated with the Framingham risk algorithm. <h3>Results:</h3> Measurable expression of UCP1 was found in 54.6% of the studied fat tissue samples. Patients on Toci had measurable expression of UCP1 in 79%, which was significantly more often than among TNFi-treated (45%, p=0.04) and MTX-treated patients (42%, p=0.02). Patients on triple therapy had also often measurable UCP1 levels compared to other groups (69% vs 43%, p=0.035). Toci patients have more lean body mass than patients treated with TNFi. This was based on lower BMI in Toci and TNFi treated patients compared to triple therapy (24.1 vs 27.1, p=0.041; 23.6 vs 27.1, p=0.017; respectively). Additionally, the estimated mucle mass by creatinin/height ratio was significantly lower in TNFi than in triple therapy (p=0.034) and Toci (p=0.008). Clinically, the treatment groups were similar in age, disease activity DAS28 and disease duration with the except for Toci. Toci patients were older (65 vs 57, p=0.04) and had numerically longer disease duration (17y vs 7y) and lower DAS28 (1.98 vs 3.11). Notably, Toci patients had significantly higher TC compared to TNFi (p=0.027), and triple therapy (p=0.041). Triple therapy had the lowest TC levels (p=0.017). The differences were due to LDL, here patients on Toci had higher LDL than TNFi (p=0.09) and triple therapy (p=0.015). Serum HDL was similar. These differences in serum lipids were not related to expression of ABCA1 or UCP1. Despite the difference in the serum lipid profile, the estimated CV risk was significantly lower in Toci compared to MTX patients (4.1[0.87-5.75] vs 6.6[3.9-9], p=0.041). <h3>Conclusion:</h3> In this study is Toci treatment is associated with persistent UCP1 production by adipose tissue. This was followed by lower estimated CV risk and favourable body composition in female RA patients. <h3>Reference:</h3> [1] Carpentier, A. C., Blondin, D. P., Virtanen, K. A., Richard, D., Haman, F., &amp; Turcotte, É. E. (2018). Brown Adipose Tissue Energy Metabolism in Humans. Frontiers in endocrinology, 9, 447. doi:10.3389/fendo.2018.00447 <h3>Disclosure of Interests:</h3> None declared