Adipokines and Autoimmunity in Inflammatory Arthritis

Abstract

Adipokines are adipose tissue-derived factors not only playing an important role in metabolism but also influencing other central processes of the body, such as inflammation. In autoimmune diseases, adipokines are involved in inflammatory pathways affecting different cell types. Many rheumatic diseases belong to the group of autoimmune diseases, for example rheumatoid arthritis (RA) and psoriatic arthritis. Due to the autoimmune responses, a chronic inflammatory milieu develops, which affects the whole body, including adipose tissue. Metabolic alterations such as obesity influence inflammatory responses in autoimmune diseases. Adipokines are bioactive mediators mainly produced by adipose tissue. Due to alterations of systemic adipokine levels, their role as biomarkers with diagnostic potential has been suggested in the context of rheumatic diseases. In the affected joints of RA patients, different synoviocytes but also osteoclasts, osteoblasts, and chondrocytes produce several adipokines, contributing to the unique inflammatory microenvironment. Adipokines have been shown to be potent modulatory effectors on different cell types of the immune system but also local cells in synovial tissue, cartilage, and bone. This review highlights the most recent findings on the role of adipokines in the pathophysiology of inflammatory arthritis with a distinct focus on RA in the quickly developing research field.

Integrative Analysis of lncRNA-mRNA Profile Reveals Potential Predictors for SAPHO Syndrome

“…Furthermore, the lncRNA-mRNA interaction networks for both cis and trans regulators were also constructed, with GO and KEGG analyses performed to gain an insight into the biological function of DE lncRNAs and their targets. Nine genes were enriched in the adipocytokine signaling pathway, while the roles of adipocytokines as diagnostic biomarkers in rheumatic disease has been suggested (Neumann et al, 2021), which showed strong modulatory properties on different effector cells in rheumatic joint diseases such as OA and RA (Carrión et al, 2019). Consistent with previous reports indicating FoxO1 in SPAHO syndrome (Berthelot et al, 2018), another nine genes including FoxO3 in the FoxO signaling pathway was also found to be regulated by DE lncRNAs in the SAPHO group.…”

Adiponectin Associates with Rheumatoid Arthritis Risk in Overweight and Obesity Independently of Other Adipokines

“…This association was independent of confounding factors, including bariatric surgery. As circulating levels of other adipokines are known to be elevated in patients with RA compared to controls, we wanted to determine if leptin, resistin, and visfatin levels were also associated with the future development of RA [9]. By performing a nested case-control study within the SOS study based on the same patients with incident RA as in our previous study matched 1:5 with controls without incident RA [25], we did not observe any association between leptin, resistin, and visfatin and the risk of future RA.…”

“…However, obesity is not only a risk factor for metabolic disturbances such as type 2 diabetes or metabolic syndrome but also for inflammatory diseases such as gout, psoriasis, and rheumatoid arthritis (RA) [3][4][5][6][7]. Adipokines, by virtue of their regulatory role in the integration between metabolism and systemic inflammation, are candidates to be involved in the pathogenesis of inflammatory diseases [8,9].…”

“…Several adipokines have been found elevated in blood from patients with RA, a systemic inflammatory disease affecting mainly the joints [10]. However, it is unknown whether they contribute to the development of the disease or if they are unspecific markers of inflammation [9]. An interesting example is adiponectin, which is the most abundant adipokine circulating in blood [11].…”

“…As opposed to other adipokines, circulating adiponectin levels are low in patients with obesity, type 2 diabetes, and metabolic syndrome [12,13]. On the other hand, circulating adiponectin levels are elevated in inflammatory conditions such as RA, and synovial fluids from patients with RA show higher concentrations of adiponectin compared to those from patients with osteoarthritis [9,14].…”