Adipokines have several effects on the immune system through regulating the expression and secretion of various cytokines. Therefore, they can play a crucial role in inflammatory diseases like IBD, which also have a metabolic background (17). Several studies have shown that, adipokines such as leptin, resistin, visfatin, retinol-binding protein-4, adiponectin, glucose, and insulin are deregulated in the IBD patients (13). Metrnl is a novel adipokin, which plays a key role in inflammation and insulin resistance improvement (18). Accordingly, this adipokine has been investigated in several metabolic and inflammatory diseases. Lee et al. showed that, the levels of Metrnl were lower in the serum samples of the T2DM patients(19). Moreover, Dadmanesh et al. found lower serum levels of Metrnl in the patients with coronary artery disease and type 2 diabetes mellitus(20). While, Chung et al. reported an increased serum level of Metrnl in the patients with T2DM(21). Most of the previous studies determined the tissues level of Metrnl in inflammatory disorders, so there is no data on the serum levels of Metrnl in these complications. Bridgewood et al. investigated the Metrnl in synovial tissue in the patients with Rheumatoid Arthritis, Psoriatic Arthritis, and Osteoarthritis. As a result, they found the elevated level of Metrnl in Psoriatic Arthritis (22). To the best of knowledge, this is the first report on the serum levels of Metrnl in the IBD patients. In addition, our results show the lower serum levels of Metrnl in the IBD patients compared to the controls. However, Metrnl was not different between the patients with UC and CD. LI et al. demonstrated that, Metrnl is highly expressed in the gastrointestinal tract of normal donors as well as mice. On the other hand, they produced intestinal epithelial cell-specific knockout mice, which showed no significant serum reduction, despite the reduction in the GUT expression of Metrnl (16). A recent study performed by Zuo et al. reported that Metrnl expression is higher in mesenteric adipose tissue (MAT) of the CD patients compared to the controls. They also showed that, systemic treatment of Metrnl can improve the adipocyte function, and reduce the macrophage infiltration and inflammation by acting on the PPARγ pathway in mice. Therefore, they suggested that, Metrnl upregulation in the MAT of these patients may be caused by a compensatory response ((14). Regarding the inconvenient results, it seems likely that, Metrnl expression can have an organ dependent pattern; however, establishing this concept needs more studies.
Furthermore, in the present study, Metrnl indicated an inverse relationship with the inflammatory cytokines in the IBD patients. Also, recent studies observed that, Metrnl displays a function in inflammation pathways. Zuo et al. administered the Metrnl in IL-10-/- mice and then observed a significant decrease in the score of inflammation and pro-inflammatory factors such as tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and IL-6 (12). Additionally, Zhi-yong LI et al. reported that, Metrnl plays a regulatory role in the expression of antimicrobial peptides such as islet-derived 3 gamma (Reg3g), lactotransferrin, and amyloid A-3 (SAA3) (22). Since TNF-α and IL-6 are considered as the markers of inflammation, our results suggest a relationship between Metrnl and IBD pathogenesis
When we stratified the population based on obesity, the serum level of Metrnl was significantly lower in obese subjects than in non-obese ones. Consistently, AlKhairi et al. reported that, Metrnl is significantly higher in the T2D obese patients, in a way that this elevation can be considered as a compensatory response (23). However, Zhi-Yong Li et al. showed no correlation between serum Metrnl level and BMI (24). As the adipose tissue is the main source of Metrnl secretion, it is expected that, BMI can affect the levels of this adipokine, and adipose tissue inflammation and dysfunction might be considered as the causes for the decrease in Metrnl levels.