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  • Review Article
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What's new in our understanding of the role of adipokines in rheumatic diseases?

Abstract

Important advances in our understanding of the relationships between adipokines, inflammation and the immune response have been achieved in the past 10 years. White adipose tissue has emerged as a highly dynamic organ that releases a plethora of immune and inflammatory mediators that are involved in numerous diseases, including not only rheumatic diseases such as rheumatoid arthritis, osteoarthritis and systemic lupus erythematosus, but also cardiovascular and metabolic complications that are frequently observed in rheumatic diseases. Our rapidly growing knowledge of adipokine biology is revealing the complexity of these amazing proteins, thereby redefining white adipose tissue as a key element of the inflammatory and immune response in rheumatic diseases. Adipokines exert potent modulatory actions on target tissues and cells involved in rheumatic disease, including cartilage, synovium, bone and various immune cells. In this Review, we describe the most recent advances in adipokine research in the context of rheumatic diseases, focusing primarily on leptin, adiponectin, visfatin and resistin, and also the potential role of newly identified adipokines such as chemerin, lipocalin 2 and serum amyloid A3.

Key Points

  • Adipose tissue, through the production of adipokines, is emerging as one of the major drivers of systemic and local inflammation in rheumatic diseases

  • Adipokines are produced predominantly by adipose tissue, but are also expressed intra-articularly by chondrocytes, synoviocytes and immune cells

  • Adipokines are emerging as modulators of rheumatic diseases by promoting and perpetuating inflammatory responses

  • Adipokine levels are associated with radiographic damage in patients with rheumatoid arthritis

  • Obesity and fat-mass dysfunction, characterized by aberrant adipokine expression, might be considered as one of the major risk factors for the development and progression of osteoarthritis

  • Therapeutic strategies aimed to counteract dysregulation of proinflammatory adipokine production could be effective in rheumatic diseases

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Figure 1: Signal transduction pathways for leptin and adiponectin receptors in chondrocytes and synovial fibroblasts.
Figure 2: The cellular targets of adipokines in rheumatic diseases.

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Acknowledgements

Part of the research described in this Review was supported by the Spanish Ministry of Health through the Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, and by the Xunta de Galicia (SERGAS). We also acknowledge the technical assistance provided by Veronica López.

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R. Gómez, J. Conde, M. Scotece, F. Lago and O. Gualillo researched data for the article. R. Gómez, J. J. Gómez-Reino, F. Lago and O. Gualillo contributed to discussions of the content. R. Gómez, J. Conde and O. Gualillo wrote the article. All authors performed review/editing of the manuscript before submission.

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Correspondence to Oreste Gualillo.

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Gómez, R., Conde, J., Scotece, M. et al. What's new in our understanding of the role of adipokines in rheumatic diseases?. Nat Rev Rheumatol 7, 528–536 (2011). https://doi.org/10.1038/nrrheum.2011.107

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