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SP0159 Adipose tissue – bystander or therapeutic target?
  1. MI Bokarewa
  1. Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden

Abstract

Adipose tissue (AT) is a complex endocrine organ with profound effects on body physiology. Research of recent years generated remarkable volume of information on metabolic and immune functions of AT. The lecture will focus on topics of AT biology that shed light on areas of interest linking metabolic, immune and rheumatic conditions.

AT is a recognized master regulator of energy balance and nutritional homeostasis. Cells of AT are active part in establishment of autoimmunity, and also osteoarthritis and osteoporosis. Macrophages enrich AT, change its phenotype and mediate inflammation, enhance antigen presentation. Th17 and regulatory T cells reside and operate in AT, having distinct transcriptional and functional characteristics from counterparts of the lymphoid organs. IL6 and IL33 signaling contribute to this distinction. Adipocytes communicate with other cell types by means of signal molecules adipokines, interleukins, and fatty acids and may affect blood pressure, muscle functions, wound healing, bone formation, hematopoiesis and tumor growth. Localization of AT plays important role for its properties including cellular composition, their gene expression profile and secretome, response to external forces and their therapeutic potential. Subcutaneous AT and bone marrow AT are most available and studied in humans.

Adiposity has been revealed as a risk factor for development of multiple autoimmune conditions including type 1 diabetes, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, psoriasis and thyroiditis. It also associates with low response rate to both biologic and non-biologic anti-rheumatic treatment. Notably, cumulative evidence show a surprising protective action of AT for radiographic joint damage in arthritis.

Antirheumatic drugs have remarkable effect on the body fat composition and serum lipid profiles, and could therefore be considered as AT-targeting agents. Impact of these drugs on the composition and function of AT localized subcutaneously and in the bone marrow remains in focus of research and will provide new insights in mechanisms of insulin resistance, cardiovascular risk, bone metabolism and autoantibody production.

Production of adipokines has been proposed a mechanism through which AT fuels inflammation and severity of autoimmune diseases however direct evidence still awaits. Several adipokine targeting and adipokine stimulating therapies have been designed and experimentally tested in the models of collagen-induced arthritis, autoimmune diabetes and insulin resistance, encephalitis, and osteoporosis induced by estrogen-deficiency. In human settings, the experience of leptin substitution in anorexia neurosa and in lipodistrophy revealed positive effects on bone metabolism and improved cognition.

In conclusion, AT attracts increasing attention as an active contributor of inflammation and autoimmunity. Further studies are needed to confirm and specify the effects and pathogenic links within AT. Novel insights in mechanisms regulating the diversity of AT composition and functions may assist conversion of AT into a teammate of anti-rheumatic processes.

Disclosure of Interest None declared

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