In the present study, the omentin gene expression was examined in adipose tissues of T1D and T2D mice models that were induced by higher and lower doses of STZ with normal pellet and HFD diet for the investigation of the effects of fat mass on insulin metabolism in different types of diabetes. Many studies have attempted to detect the associations between serum omentin levels and different types of diabetes. However, a few studies have been carried out to find the molecular mechanism of the variation of omentin gene expression in different types of diabetes and its relationship with serum biochemical parameters in T1D and T2D.
The obtained results of this study revealed that the plasma insulin levels were significantly decreased in type 1 diabetic mice. In addition, there was a significant increase in insulin levels in HFD + STZ type 2 diabetic mice. However, no significant difference was observed in NPD + STZ type 2 diabetic mice, compared to the control group.
Regarding the plasma omentin levels, there was a significant difference in T1D and NPD + STZ model of T2D; nonetheless, omentin levels in T2D with HFD + STZ were not statistically significant. However, the investigation of omentin gene expression in adipose tissues of the studied groups showed that the omentin expression level was significantly higher in T1D mice; however, the omentin expression resulted in a significant reduction in both models of T2D mice.
Despite no significant differences in plasma omentin levels in HFD + STZ type 2 diabetes, the obtained results revealed that the omentin levels of HFD + STZ mice were lower than those of T1D. In addition, the gene expression of omentin in adipose tissues of HFD + STZ mice was significantly lower than those of both T1D and control groups. These results suggested that the circulating omentin concentrations may not always be associated with adipose tissue mass and the physiological/hormonal role of omentin may be local in insulin signaling.
It has been shown that the dose-dependent administration of glucose and insulin to human omental adipose tissues results in a reduction of omentin-1 expression. In addition, insulin–glucose infusion in healthy individuals can significantly decrease plasma omentin-1 concentration. Therefore, the above-mentioned results revealed that omentin-1 production is under glucose and insulin regulation [23].
It has demonstrated that the underweight individuals had higher plasma omentin-1 level than those who were overweight. Furthermore, plasma omentin-1 inversely correlated with body mass index and insulin resistance; however, it was positively associated with HDL-C levels. It has also shown that the omentin gene expression decreased with obesity. Taken together these results clearly show that obesity reduces serum omentin-1 concentration in adults and adolescents [3].
It has reported that omentin is preferentially expressed in mouse intestinal Paneth cells [13]. However, the results of several studies have shown that omentin gene is mainly expressed in human visceral adipose tissue. Moreover, it has observed that omentin is scarcely expressed in mouse visceral adipose tissue. These findings suggest that omentin may play a more important role in adipose tissue of humans than in mice [12, 24].
In the present study, it was demonstrated that omentin was expressed in adipose tissues of C57BL/6 mice and its expression is changed in different types of diabetes. According to the results of the present study, it was revealed that the omentin mRNA levels in T1D model increased 3.68-fold and had a positive correlation with serum omentin levels. Moreover, the omentin mRNA levels in T2D models, including HFD + STZ and NPD + STZ, were attenuated to 0.31- and 0.15-fold, respectively. There was also no significant correlation between the related mRNA levels and serum omentin levels. However, a negative association was observed between omentin mRNA and serum ALT levels in HFD + STZ model.
Based on the obtained results of the present study, it was also shown that omentin gene expression had a positive correlation with the animal weight, while it had a negative relation with the fasting blood glucose in NPD + STZ model. These findings reflected that not only omentin was expressed in mice visceral adipose tissue but also it can change based on different metabolic conditions.
It has reported that the omentin concentrations of fasting and 2 h following oral glucose tolerance test were significantly decreased in diabetic subjects, as well as in subjects with IGT (impaired glucose tolerance) when compared to the control group [6]. In addition, it was observed that plasma omentin concentrations in pre-diabetic or diabetic obese patients were lower than the cases with normal fasting blood glucose in a cross-sectional study [25]. Furthermore, there was a significantly reduced serum omentin concentration in T2D patients with gender and BMI adjusted with healthy controls. Moreover, their results reflected that serum omentin level negatively correlated with BMI, fasting blood glucose, and HOMA-IR [19]. According to the findings of the aforementioned study, it was revealed that the serum omentin-1 levels are not affected only by the increase of fat mass and more omentin concentrations can be affected by insulin and glucose variations. In the current study, serum omentin concentrations in T2D mice, which were induced by NPD and lower doses of STZ, were reduced, followed by the decreased gene expression in adipose tissues. However, the serum omentin levels in T2D mice induced with HFD and a low dose of STZ did not decrease and were not compatible with its decreased gene expression in adipose tissue. Thus, there may be other sources for circulating omentin. Similar to above studies [6, 19], the findings of the present study revealed that serum omentin levels could be reduced in T2D, although it may not be observed in all the conditions of T2D.
It is reported serum omentin concentration was significantly lower in children with T1D than in control children [5]. However, in current study, serum omentin concentrations in T1D mice raised, followed by the increased gene expression in adipose tissues.
It has shown that serum omentin level is significantly reduced in obese mice, compared to the non-obese ones [18]. However, another study demonstrated that serum omentin levels were similar between obese and non-obese groups [26]. Similarly, it was no significant difference between the obese diabetic mice and non-obese normal controls in this study.
It has demonstrated that serum omentin level was increased in diabetic rats induced with STZ [27]. Similarly, both adipose tissues related to omentin gene expression and serum omentin levels in T1D model were increased in the current study. Since the insulin production was suppressed in T1D mice, it hypothesized that the omentin gene expression and its serum levels rise to compensate the insulin deficiency in type 1 diabetes.
In a study that was conducted to experimental T2D in rats, there was no change in omentin levels in the groups including HFD and low dose of STZ [28]. Similarly, the serum omentin levels in C57BL/6 T2D mice induced with HFD and a low dose of STZ did not significantly change in the present study.
The obtained results of the present study showed that the omentin mRNA levels may be affected by the changes of fat tissue mass in mice model. Moreover, the changes in serum omentin levels could depend on different metabolic conditions. On the other hand, the source of serum omentin may be different according to different health and disease conditions.