Arias de la Rosa, IvánEscudero-Contreras, AlejandroRuiz-Ponce, MiriamRomán-Rodríguez, CristóbalPérez-Sánchez, CarlosÁbalos-Aguilera, María del CarmenOrtega-Castro, RafaelaAlcaide, JuanMurri, MoraFont, PilarCalvo-Gutiérrez, JerusalemLuque-Tevar, MariaPatiño-Trives, Alejandra MariaGuzmán-Ruiz, RocíoMalagón, Maria del MarTinahones, Francisco JoséCollantes-Estévez, EduardoLópez-Pedrera, CharyBarbarroja, Nuria2022-09-282022-09-282021-10-13Arias de la Rosa I, Escudero-Contreras A, Ruiz-Ponce M, Román-Rodríguez C, Pérez-Sánchez C, Ábalos-Aguilera MDC, et al. Changes in the Adipose Tissue Induced by Rheumatoid Arthritis: Effects of Disease-Modifying Anti-Rheumatic Drugs. Front Immunol. 2021 Oct 13;12:744022http://hdl.handle.net/10668/4179Disease 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Rheumatoid arthritisObesityInflammationAdipose tissuecDMARDsLeflunomideHydroxychloroquineMethotrexateArtritis reumatoideObesidadInflamaciónTejido adiposoAntirreumáticosLeflunomidaHidroxicloroquinaMetotrexatoMedical Subject Headings::Anatomy::Tissues::Connective Tissue::Adipose TissueMedical Subject Headings::Persons::Persons::Age Groups::AdultMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antirheumatic AgentsMedical Subject Headings::Diseases::Immune System Diseases::Autoimmune Diseases::Arthritis, RheumatoidMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cross-Sectional StudiesMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Persons::Persons::Age Groups::Adult::Middle AgedMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::ObesityMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Quinolines::Aminoquinolines::Chloroquine::HydroxychloroquineMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Pteridines::Pterins::Aminopterin::MethotrexateMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammationresearch article34721412open access10.3389/fimmu.2021.7440221664-3224PMC8549628