RT Journal Article
T1 Molecular Changes in the Adipose Tissue Induced by Rheumatoid Arthritis: Effects of Disease-Modifying Anti-Rheumatic Drugs.
A1 Arias de la Rosa, Iván
A1 Escudero-Contreras, Alejandro
A1 Ruiz-Ponce, Miriam
A1 Román-Rodríguez, Cristóbal
A1 Pérez-Sánchez, Carlos
A1 Ábalos-Aguilera, María Del Carmen
A1 Ortega-Castro, Rafaela
A1 Alcaide, Juan
A1 Murri, Mora
A1 Font, Pilar
A1 Calvo-Gutiérrez, Jerusalem
A1 Luque-Tevar, Maria
A1 Patiño-Trives, Alejandra Maria
A1 Guzmán-Ruiz, Rocío
A1 Malagón, Maria Del Mar
A1 Tinahones, Francisco José
A1 Collantes-Estévez, Eduardo
A1 López-Pedrera, Chary
A1 Barbarroja, Nuria
K1 adipose tissue
K1 cDMARDs
K1 hydroxychloroquine
K1 inflammation
K1 leflunomide
K1 methotrexate
K1 obesity
K1 rheumatoid arthritis
AB Disease severity, progression and response to therapy might be worse in obese rheumatoid arthritis (RA) patients, but paradoxically, obesity also might protect from radiographic joint damage. Thus, the intricate relationship between obesity and RA needs urgent clarification. The aim of this study was to assess the influence of obesity on the onset and development of RA and to determine whether arthritis could modify the adipose tissue biology and whether conventional Disease Modifying Anti-Rheumatic Drugs (cDMARDs) can modulate these alterations. Two strategies were followed: (1) clinical profiling of two cohorts of RA: non-obese and obese patients; and (2) mechanistic studies carried out in both a collagen-induced arthritis (CIA) in an obese mouse model and 3T3-L1 adipocytes treated with cDMARDs (leflunomide, methotrexate, and hydroxychloroquine). In our cohort of RA patients with low-moderate disease activity, the presence of obesity was not related to a higher activity of the disease; actually, disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR) was reduced in the obese RA patients. However, the induction of arthritis promoted transcriptomic changes in the adipose tissue under obesity condition in the obese CIA model. Treatment with hydroxychloroquine reduced weight and insulin resistance, accompanied by beneficial metabolic effects in the adipose tissue. These molecular changes in adipose tissue were also observed after methotrexate administration. In sum, arthritis might affect directly the inflammatory burden and metabolic alterations associated with obesity in adipose tissue. Clinicians should be cautious measuring the activity of the disease in obesity and managing the best therapeutic options for the metabolic comorbidities of these patients, where the combination of hydroxychloroquine and methotrexate should be considered to improve adipose tissue dysfunction in obese RA.
YR 2021
FD 2021-10-13
LK https://hdl.handle.net/10668/25869
UL https://hdl.handle.net/10668/25869
LA en
DS RISalud
RD Apr 6, 2025