Discussion
The aim of the present meta-analysis was to investigate possible differences between CD or UC patients and healthy controls in serum resistin levels. The result confirmed that higher resistin levels in CD, UC patients than in healthy individuals. In subgroup analyses stratified by region, we observed that the serum resistin levels of CD and UC patients in Europe were higher, indicating region may be associated with serum resistin concentrations. Moreover, meta-regression for serum resistin levels indicated that publication year may be an explanation for the high heterogeneity across the studies.
Adipokines appear to drive metabolic alterations, pro-inflammatory as well as anti-inflammatory, and human resistin can stimulate the pro-inflammatory cytokines by NF-kappaB (NF-k B) pathway25 . Resistin was extensively studied in rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, psoriasis and osteoarthritis26-28 . It can bind toll-like receptor 4 (TLR4) on human leukocytes and increase the producing of pro-inflammatory cytokines, such as interleukin(IL)-6, IL-12 and IL-1β, in turn, these cytokines also enhance resistin expression 29 . It also can stimulate tumor necrosis factor(TNF)-α secretion and activate NF-k B25 . Furthermore, resistin is associated with disease activity, drug use, blood glucose level, glucose tolerance and insulin resistance30 ,31 . Taken together, the resistin has been comfirmed to play a crucially role in autoimmune diseases, inflammatory as well as various metabolic.
The causes of the aberrant immune response in IBD patients is unclear, CD might result from the interaction between enetic predisposition, environmental factors, and altered gut microbiota, leading to hyperactive gut-associated immune response32 . In contrast with CD, the UC inflammation is limited to the colonic mucosa and genetic, dietary, and environmental risk factors may also play an pivotal role in the etiology33 . IBD patient is typically characterized hypertrophy of the mesenteric adipose tissue and alterations in local or serum adipokine concentrations34 . Our result confirmed that higher resistin concentrations in CD, UC patients. Although the etiology of IBD remains unkonwn, resistin may act as a new serological biomarkers of IBD.
Subgroup analyses stratified by region showed elevated serum resistin levels in CD and UC patients in the studies conducted in Europe, indicating the presence of regional differences. However, heterogeneity was high in the meta-analysis that compared serum resistin levels between CD and UC patients and healthy controls. Meta-regression and subgroup analysis were performed to detect the potential reasons of heterogeneity. Studies have demonstrated positive relationships between obesity and IBD risk35 . In meta-regression analysis, year of publication, size of sample, age of cases, BMI of cases were incorporated as covariates, the results suggested that the source of heterogeneity may come from publication year.
To our knowledge, the current study shows the first meta-analysis that combines all published studies and presents the differences of resistin concentrations in CD, UC patients. Several limitations deserve to be considered in our study. Firstly, the heterogeneity among studies was high. Secondly, studies evaluating resistin in CD and UC are limited and insufficient data might account for the high heterogeneity among these studies. Future studies examining the resistin concentrations in a larger number of CD and UC patients are required.
In summary, the levels of resistin are significantly elevated in CD and UC patients compared with healthy controls, suggesting a pivotal role of resistin in IBD pathogenesis.