TABLE 1.

Summary of effects of known adipokines on obesity and metabolic, rheumatic, and cardiovascular diseases.

Adipokine	Obesity and metabolic dysfunction	Rheumatic diseases	Cardiovascular disease
Leptin	Hyperleptinemia is positively correlated with obesity and metabolic dysfunction, decreases food intake, increases energy expenditure and insulin resistance (Rosenbaum and Leibel, 1999; Ahima et al., 2000; Schwartz et al., 2000; Hafizuallah, 2006; Al-Amodi et al., 2018)	Hyperleptinemia is associated with erosions in patients with RA (Lee et al., 2007; Yoshino et al., 2011; Olama et al., 2012; Cao et al., 2016; Lee and Bae, 2016)	Hyperleptinemia is associated with protrombotic effects, endothelial dysfunction, cardiovascular remodeling; leptin regulates cardiac contractile function, metabolism, cell size, and production of extracellular matrix components in cardiomyocytes (Beltowski, 2006; Momin et al., 2006; Adiarto et al., 2007; Katsiki et al., 2018)
Adiponectin	Hypoadiponectinemia is associated with obesity, insulin resistance, T2DM, and metabolic syndrome (Arita et al., 1999; Hotta et al., 2000; Weyer et al., 2001; Mohan et al., 2005; Gilardini et al., 2006; Yamauchi et al., 2007; Wang et al., 2008)	Hyperadiponectinemia was found in chronic inflammatory RA (Neumann et al., 2011; Fatel et al., 2018)	Hypoadiponectinemia is associated with hypertension, endothelial dysfunction, elevated myocardial hypertrophy (Diah et al., 2019)
Resistin	Hyper-resistinemia is associated with obesity and insulin resistance (Rajala et al., 2004; Rangwala et al., 2004; Schäffler et al., 2004; Vendrell et al., 2004; Satoh et al., 2014)	Higher resistin levels were found in serum and synovial fluid of RA patients. It accumulates in the inflamed joints of RA patients inducing the development of arthritis accompanied by leukocytic infiltration and hyperplasia of the synovium (Kassem et al., 2010)	Hyper-resistinemia is associated with cardiovascular risk, endothelial dysfunction, and hypertension (Takata et al., 2008; Zhang L. et al., 2010; Thomopoulos et al., 2011)
Chemerin	Hyperchemerinemia is positively associated with markers of inflammation and components of the metabolic syndrome. Possible link between chemerin, obesity, and T2DM development. Chemerin stimulates insulin sensitivity in adipose tissue (Bozaoglu et al., 2007; Ernst et al., 2010)	Chemerin is present in synovial fluids of RA and OA, stimulates the leukocyte migration into the joint and the pro-inflammatory markers in synovial fibroblasts from RA patients (Buechler, 2014; Fatima et al., 2014; Mariani and Roncucci, 2015)	Hyperchemerinemia is associated with cardiovascular risks in patients with metabolic syndrome (Wu et al., 2020)
LCN2	LCN2 is associated with low level systemic inflammation in metabolic syndrome and obese patients (Jang et al., 2012; Abella et al., 2015)	Higher LCN2 concentrations in SF of RA patients (Gupta et al., 2007; Katano et al., 2009; Staikos et al., 2013)	Higher LCN2 levels are significantly associated with heart failure, coronary heart disease, and stroke (Hemdahl et al., 2006; Folkesson et al., 2007; Sivalingam et al., 2017)
Vaspin	Higher serum vaspin levels in subjects with obesity and T2DM (Feng et al., 2014)	Low serum vaspin concentration in OA patients (Bao et al., 2014) Higher serum vaspin levels in psoriatic arthritis and RA patients (Ozgen et al., 2010; Colak et al., 2019)	Low vaspin levels are associated with coronary artery disease severity (Kadoglou et al., 2011)
Omentin-1	Low omentin-1 levels are associated with obesity. Omentin-1 enhances the effect of insulin on glucose metabolism (de Souza Batista et al., 2007)	Hypo-omentinemia is associated with chronic inflammatory RA (Senolt et al., 2010) Low omentin-1 concentrations in SF are detectable in patients with RA (Li Z. G. et al., 2012)	Omentin-1 concentrations are inversely correlated with cardiovascular disease thanks its vasodilating effect (Tsuji et al., 2001; Yamawaki et al., 2010, 2011; Duan et al., 2011)
FSTL1	Overweight and mild obesity might be associated with increased FSTL1 levels (Horak et al., 2018)	Controversial data (FSTL1 promotes and/or inhibits inflammation in CAIA model) (Mattiotti et al., 2018)	Higher FSTL1 circulating concentrations were found in patients with heart failure and acute coronary syndrome (Oshima et al., 2008)
SPARC	Overexpression of SPARC modulates the expression levels of various pro-inflammatory cytokines, critically involved in insulin resistance, glucose, and lipid metabolism during adipogenesis (Termine et al., 1981; Shen et al., 2014)	Higher SPARC levels in synovial fibroblasts from patients with RA or OA (Bradshaw et al., 2003; Delany et al., 2003; Robey and Boskey, 2003)	SPARC-induced positive effect in the acute phase of myocardial infarction (Myasoedova et al., 2018)
SFRP5	Plasma concentrations of SFRP5 are unfavorably correlated with obesity (Schulte et al., 2012)	SFRP5 suppresses the inflammatory response in fibroblast-like synoviocytes of RA patients, inhibiting WNT signaling (Kwon et al., 2014)	Serum SFRP5 levels are inversely related to coronary artery disease, development of atherosclerosis, and vascular function (Safoura and Gholam, 2018)
CTRPs	Higher CTRP6 levels in obesity (Lei et al., 2017)	CTRP3 promotes proliferation of chondrocytes (Maeda et al., 2006)	CTRP3 is involved in progressive remodeling after myocardial infarction, exerts vasoprotective effects (Schäffler and Buechler, 2012)
FAM19A5	FAM19A5 concentrations were significantly elevated in patients with T2DM (Tourniaire et al., 2013)	Studies on rheumatic disease are limited	FAM19A5 prevented post-injury neointima formation in rat carotid arteries and mouse femoral arteries in vivo (Wang et al., 2018)
WISP1	Higher WISP1 circulating levels in obese and insulin resistance patients (Sahin Ersoy et al., 2016)	High WISP1 levels are harmful to cartilage integrity in osteoarthritic patients (van den Bosch et al., 2019)	WISP1 regulates cardiac endothelial signaling and contributes to beneficial effects in MI (Price et al., 2004; Reddy et al., 2011; Liu et al., 2013)
PGRN	Hyperprogranulinemia is associated with obesity-associated insulin resistance (Youn et al., 2009; Qu et al., 2013; Shafaei et al., 2016)	Hyperprogranulinemia is associated with RA (Cerezo et al., 2015; Abella et al., 2016)	PGRN improves tissue repair by active recruitment of leukocytes and increasing capillary perfusion after acute injury (Jian et al., 2012)
Nesfatin-1	Low serum nesfatin-1 levels were found in obesity and metabolic syndrome (Gonzalez et al., 2011)	Positive association between blood serum nesfastin-1 levels and CRP in RA patients (Kvlividze et al., 2019)	Decreased plasma nesfatin-1 levels in patients with acute myocardial infarction (Ramesh et al., 2017)
Visfatin/PBEF/NAMPT	Hypervisfatinemia is associated with obesity, T2DM, and metabolic syndrome (Chang et al., 2011)	Higher serum visfatin levels in RA patients (Meier et al., 2012; Neumann et al., 2016)	Hypervisfatinemia is associated with cardiovascular disease (Xiao et al., 2009; Anfossi et al., 2010)
Apelin	Higher apelin levels in obese patients (Heinonen et al., 2005; Schinzari et al., 2017; Bertrand et al., 2018)	Lower apelin levels in early stage RA patients (Di Franco et al., 2012)	Hypoapelinemia is associated with severe chronic heart failure (Chong et al., 2006)
RBP4	RBP4 levels were positively associated with BMI (Aeberli et al., 2007; Haider et al., 2007; Jia et al., 2007; Klöting et al., 2007)	Elevated RBP4 serum levels are associated with increased risk of insulin resistance in patients with early and untreated RA (Wei et al., 2019)	Higher serum RBP4 levels in patients with cardiovascular diseases, atherosclerosis, and hypertension (Rychter et al., 2020)
PAI-1	PAI-1 levels increase in subjects with obesity, metabolic syndrome, and T2DM (Vague et al., 1986; Juhan-Vague et al., 2003; Bilgili et al., 2008)	Elevated PAI-1 levels in patients with SLE but no in RA (Bae and Lee, 2020)	Elevated plasma PAI-1 concentrations in blood and in coronary plaques of metabolic syndrome patients (Zorio et al., 2008)