Adiponectin Deregulation in Systemic Autoimmune Rheumatic Diseases.

Neža Brezovec,Katja Perdan-Pirkmajer,John Varga,Katja Lakota,Saša Čučnik,Snežna Sodin-Šemrl

doi:10.3390/ijms22084095

Abstract

Deregulation of adiponectin is found in systemic autoimmune rheumatic diseases (SARDs). Its expression is downregulated by various inflammatory mediators, but paradoxically, elevated serum levels are present in SARDs with high inflammatory components, such as rheumatoid arthritis and systemic lupus erythematosus. Circulating adiponectin is positively associated with radiographic progression in rheumatoid arthritis as well as with cardiovascular risks and lupus nephritis in systemic lupus erythematosus. However, in SARDs with less prominent inflammation, such as systemic sclerosis, adiponectin levels are low and correlate negatively with disease activity. Regulators of adiponectin gene expression (PPAR-γ, Id3, ATF3, and SIRT1) and inflammatory cytokines (interleukin 6 and tumor necrosis factor α) are differentially expressed in SARDs and could therefore influence total adiponectin levels. In addition, anti-inflammatory therapy could also have an impact, as tocilizumab treatment is associated with increased serum adiponectin. However, anti-tumor necrosis factor α treatment does not seem to affect its levels. Our review provides an overview of studies on adiponectin levels in the bloodstream and other biological samples from SARD patients and presents some possible explanations why adiponectin is deregulated in the context of therapy and gene regulation.

Highlights

We concluded that diseases with less prominent inflammation (SSc), where adipocytes have been shown to be reduced at the site of disease pathology, have decreased adiponectin levels and a negative correlation with disease activity
Treatment used in SARDs is associated with either decreased adiponectin levels, as with Janus kinases (JAKs) inhibitors, or increased levels, as in cases where GC, CY, TCZ and disease-modifying antirheumatic drugs (DMARDs) are used (Figure 7)
The paradox of why increased adiponectin levels are present in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) despite high levels of proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) could be explained at the level of adiponectin gene regulation

Summary

Introduction

Its expression is downregulated by various inflammatory mediators, but paradoxically, elevated serum levels are present in SARDs with high inflammatory components, such as rheumatoid arthritis and systemic lupus erythematosus. Regulators of adiponectin gene expression (PPAR-γ, Id3, ATF3, and SIRT1) and inflammatory cytokines (interleukin 6 and tumor necrosis factor α) are differentially expressed in SARDs and could influence total adiponectin levels. Anti-tumor necrosis factor α treatment does not seem to affect its levels. Our review provides an overview of studies on adiponectin levels in the bloodstream and other biological samples from SARD patients and presents some possible explanations why adiponectin is deregulated in the context of therapy and gene regulation. Adiponectin expression is downregulated by inflammatory mediators such as interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α).

Methods

Results

Conclusion