Table 2: Overview of main experimental and clinical data on adipocytokines in RA.

AdipocytokineModel Finding(s)Authors

AdiponectinHuman (synovial tissue) Strongly expressed in synovium and adipose tissue
Stimulates the release of IL-6 and pro-MMP-1 by RASF
Ehling et al. [62]
Human (serum)Levels significantly higher in patients with severe disease evaluated by radiographic changesEbina et al. [77]
Human (SF, synovial tissue)Levels in SF significantly higher than in OA patients
Stimulates the production of proinflammatory mediators by RASF at the same level as IL-1β
Choi et al. [65]
Human (serum)Association of serum levels with radiographic progression (stronger in patients with longer disease duration)
Levels decreased as visceral fat area increased
Giles et al. [85]
Human (plasma)Higher levels compared to healthy controls
No difference in patients with early and chronic disease
Laurberg et al. [84]
Human (synovial tissue)Induces gene expression and synthesis of proinflammatory mediators in RASF, lymphocytes, endothelial cells, chondrocytesFrommer et al. [64]
Human (serum)Association of average levels with radiographic progression, especially in certain subgroups (women, BMI < 30 kg/m2, baseline biological drugs)Giles et al. [78]
Human (serum)Association with proinflammatory cytokines
Levels positively associated with radiographic progression over 4 years
Negative correlation with BMI
Klein-Wieringa et al. [79]
Human (synovial tissue)Secretion of proinflammatory mediators mostly induced by HMW/MMW-enriched adiponectin, weakest response seen with trimeric formFrommer et al. [32]

















Leptin
Human (serum)Levels not different from those in healthy controls
Positive correlation with percent body fat in patients and controls
Anders et al. [88]
Human (serum)Levels higher than controlsSalazar-Páramo et al. [92]
Murine (synovial tissue, serum)Less severe arthritis and lower mRNA levels of proinflammatory cytokines in leptin-deficient miceBusso et al. [67]
Human (plasma, SF)Plasma levels higher than controls
Plasma levels higher than matched SF
MTX treatment associated with high plasma levels
Bokarewa et al. [93]
Human (plasma)Levels not different from those in healthy subjects
Levels inversely correlated with CRP and IL-6 levels at baseline and not modified after a short-course of anti-TNF treatment
Popa et al. [89]
Human (serum)Tendency to higher levels than controls
Strong correlation with fat mass
Toussirot et al. [94]
Human (plasma)Levels higher than controls
Positive correlation with CRP
Otero et al. [55]
Human (plasma, SF)Plasma levels not different from those in healthy controls
Positive correlation of plasma levels with BMI in patients and controls
No correlation of plasma and SF levels with disease activity
Hizmetli et al. [90]
Human (serum)Levels not different from those in OA patients
Positive correlation between serum levels and BMI
No correlation between serum levels and disease activity
Wisłowska et al. [91]
Human (serum)Higher mean levels in patients with high activity
Levels significantly correlated with disease activity
Lee et al. [56]
Human (serum)Levels higher than controls
Positive correlation between serum levels and BMI
Rho et al. [95]
Human (serum)No association with radiographic progressionGiles et al. [78, 85]
Human (serum)Association with higher insulin resistance
Increasing concentrations attenuated the increased risk of coronary calcification related to insulin resistance
Rho et al. [99]
Human (serum)Positive correlation with BMI
No association with radiographic progression
Klein-Wieringa et al. [79]
Human (serum, SF)Serum levels and synovial/serum ratio higher than controls
Synovial leptin and synovial/serum leptin ratio in patients with effusion significantly higher than in control subjects with traumatic effusion
Serum levels in patients with effusion higher than matched synovial levels
Serum levels and synovial/serum ratio significantly correlated with disease activity
Olama et al. [96]

ResistinMurine (synovial tissue)
Human (PBMCs, SF)
Induces an RA-like inflammatory destructive polyarthropathy
Marked induction in PBMCs and SF cells of the genes for proinflammatory cytokines
Levels in SF higher than matched circulating levels
Bokarewa et al. [69]
Human (serum)No association with radiographic progressionGiles et al. [78, 85]
Human (serum)Positive correlation with BMI
Association with proinflammatory cytokines
Klein-Wieringa et al. [79]

VisfatinHuman (serum)Positive correlation with IL-6 and TNF
Levels significantly higher in ACPA-positive patients
Associated with radiographic progression over 4 years
Klein-Wieringa et al. [79]

MMP: matrix metalloproteinase; RASF: rheumatoid arthritis synovial fibroblasts; SF: synovial fluid; OA: osteoarthritis; BMI: body mass index; HMW: high molecular weight; MMW: middle molecular weight; MTX: methotrexate; CRP: C-reactive protein; TNF: tumor necrosis factor; RA: rheumatoid arthritis; PBMCs: peripheral blood mononuclear cells; ACPA: anti-citrullinated protein/peptide antibodies.