The results of present study showed that flaxseed supplementation in patients with UC led to a significant reduction in the resistin and visfatin concentration. Also, we found a significant improvement in the adiponectin level in the intervention group than control.
In recent years, various studies have investigated the role of different adipokines in the pathogenesis of chronic diseases. Adipokines have both pro- and anti-inflammatory effects in IBD patients. Some studies show an increase in leptin concentration in patients with UC despite weight loss, anorexia and enhanced release of TNF-α. Increased leptin concentration is associated with exacerbation of inflammation in patients with UC[16]. Adiponectin as one of the adipokines secreted from adipose tissue has shown anti-inflammatory effects in various studies[17, 18].
We found that adiponectin concentration increased significantly after the flaxseed supplementation. Weigert et al. in a cross sectional study were showed that circulating levels of chemerin and adiponectin are higher in ulcerative colitis[19]. Also, Karmiris et al. [20]described significantly elevated adiponectin levels in UC, whereas Valentini et al.[6] identified reduced adiponectin in the serum of CD and UC patients. Waluga et al., in a study examining the effect of corticosteroid therapy on adipokine concentrations in forty patients with UC, showed that no significant differences in adiponectin concentrations were observed at baseline and end of the study between the two groups[5].
One of the reasons for the difference in the results observed in different studies is the higher concentration of adiponectin in women compared to men and the lack of proper distribution of participants in different studies in terms of sex [21]. Various studies have shown that adiponectin has the ability to exert anti-inflammatory effects by increasing the synthesis of interleukin receptor antagonist and decreasing the dendritic cell release of interferon gamma. Adiponectin also has the ability to induce macrophages to perform more phagocytosis[22, 23].
On the other hand, in line with the results of our study, some findings have indicated an increase in the concentration of adiponectin following supplementation with flaxseed. Haidari et al. were reported an increase in the adiponectin levels after the flaxseed supplementation in women with polycystic ovary syndrome[24]. Also, Sekine et al. showed that ALA-rich flaxseed oil (FSO) oral administration in rats led to a significant increase in the adiponectin levels[25].
However, the results of some studies are contradictory and no significant change in adiponectin concentration was observed following flaxseed supplementation[26, 27]. ALA, the main component of flaxseed products, acts as a ligand for PPAR-γ, which can increase expression and circulating level of adiponectin[28]. Some researchers have also reported that one of the reasons for the increase in adiponectin concentration after the flaxseed supplementation is weight loss. It has been reported that adiponectin levels and its gene expression increased following weight loss[29]. On the other hand, flaxseed can cause weight loss due to their high fiber content and active ingredients[30]. However, in our study, no significant change was observed in the weight of patients in the intervention group compared to the control group.
Resistin expression in human monocytes was markedly increased by treatment with endotoxin and pro-inflammatory cytokines[31, 32]. Based on the findings of various studies, the serum level of resistin is strongly associated with the concentration of some inflammatory factors[33, 34]. Konrad et al. showed that patients with UC had significantly higher concentration of resistin[35]. Also, Abedimanesh et al. observed that resistin levels was higher in patients with UC compared healthy subjects and correlated with disease activity scores, hs-CRP levels and fat mas[36]. Resistant plays an important role in exacerbating chronic inflammation by inducing nuclear factor-kappa B inflammatory pathways[37]. Bokarewa et al. reported that higher levels of resistin can upregulate IL-6 and TNF-a related genes [38]. Another study revealed that human resistin significantly increase the production and secretion of TNF-a and IL-12 by activation of NF-kB transcription factor[39]. In the present study, we found a significant reduction in the resistin concentration after the flaxseed supplementation. According to our search, no previous study has evaluated the effect of flaxseed on resistin concentration. However, it seems that these positive effects may be due to the high content of ALA in flaxseed.
Another result of the present study was the significant effect of flaxseed supplementation on the concentration of visfatin in patients with UC. Moschen et al. reported that visfatin can increase production and secretion of inflammatory cytokines and may be considered a new pro inflammatory adipocytokine[40]. Also, it has been reported that visfatin plasma levels and its mRNA expression significantly increased in the patients with UC[6]. Researchers have suggested that visfatin exacerbates IBD through a variety of mechanisms. These mechanisms include effects on peripheral blood mononuclear cells, direct stimulation of pro-inflammatory cytokine production and suppression of neutrophil apoptosis[41, 42]. Moreover, it has been reported that visfatin has also been shown to increase the expression of some genes involved in inflammatory pathways, such as NF-κB p65(RelA) DNA-binding activity in human leukocytes by p38 and MEK-1 [43, 44].
Prior to our study, no study evaluated the effect of flaxseed supplementation on visfatin concentration. However, some studies have shown that omega-3 supplementation significantly reduces serum visfatin concentrations[45, 46].
Our study was the first clinical trial to evaluate the effect of flaxseed supplementation on adipokine levels in patients with UC. However, there were some limitations in the present study that should be considered in analyzing the results. In this study, serum leptin concentration was not assessed. Due to the strong correlation between leptin concentration and the severity of inflammation, evaluation of this factor could increase the accuracy of the results. On the other hand, measuring the expression of genes related to some inflammatory factors could be helpful. On the other hand, one of the most important limitations of this study was the type of study design, which due to the lack of a suitable placebo, the possibility of double blinding in the study was not provided.