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Molecular Changes in the Adipose Tissue Induced by Rheumatoid Arthritis: Effects of Disease-Modifying Anti-Rheumatic

Iván Arias de la Rosa1, Alejandro Escudero-Contreras1, Miriam Ruiz-Ponce1

  • 1Rheumatology Service/Deparment of Medicine and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC), University of Cordoba, Reina Sofia Hospital, Cordoba, Spain.

Frontiers in Immunology
|November 1, 2021
PubMed

Insights

Obesity in rheumatoid arthritis (RA) may alter adipose tissue biology. Certain disease-modifying anti-rheumatic drugs (DMARDs) like hydroxychloroquine and methotrexate can improve metabolic dysfunction in obese RA patients.

Area of Science:

  • Rheumatology
  • Metabolic Disease
  • Immunology

Background:

  • The relationship between obesity and rheumatoid arthritis (RA) is complex, with conflicting evidence regarding disease severity and joint damage.
  • Understanding how obesity influences RA pathogenesis and adipose tissue biology is crucial for effective treatment.

Purpose of the Study:

  • To investigate the impact of obesity on RA onset and progression.
  • To determine if arthritis affects adipose tissue and if conventional disease-modifying anti-rheumatic drugs (cDMARDs) can modulate these changes.

Main Methods:

  • Clinical profiling of non-obese and obese RA patient cohorts.
  • Mechanistic studies using a collagen-induced arthritis (CIA) obese mouse model and 3T3-L1 adipocytes treated with cDMARDs (leflunomide, methotrexate, hydroxychloroquine).

Main Results:

  • Obesity did not correlate with higher disease activity in RA patients; DAS28-ESR was lower in obese RA patients.
  • Arthritis induction caused transcriptomic alterations in adipose tissue of obese mice.
  • Hydroxychloroquine and methotrexate treatments improved weight, insulin resistance, and adipose tissue metabolism.

Conclusions:

  • Arthritis can directly impact the inflammatory and metabolic burden in adipose tissue associated with obesity.
  • Clinicians should carefully assess disease activity and manage metabolic comorbidities in obese RA patients.
  • Combination therapy with hydroxychloroquine and methotrexate may improve adipose tissue dysfunction in obese RA.
Keywords:
adipose tissuecDMARDshydroxychloroquineinflammationleflunomidemethotrexateobesityrheumatoid arthritis

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