3.2. Agomelatine treatment improves the inflammatory status in obese mice.
Non-treated HFD mice displayed an amplified expression of Tnf-α ,Il-1β , Il-6 and monocyte chemotactic protein 1 (Mcp-1 ) in adipose tissue (Figure 4A) and liver (Figure 4A), compared to control mice. All the treatments reduced the expression of those pro-inflammatory mediators in the liver, but only agomelatine reduced their expression in fat tissue (Figure 4A). Likewise, the expression of Jnk-1 was significantly up-regulated in the liver of untreated obese mice in comparison with non-obese ones, which was also significantly lowered by all treatments (Figure 4B).
Elevated fat expression of leptin in the HFD group (Figure 4C) was linked to a decreased expression of leptin receptors in liver and fat (Figure 4C). Regarding adiponectin, obese mice presented a lower expression in adipose tissue\sout. However, agomelatine and metformin were able to significantly increase them (Figure 4C).
Expression of Glut-4 in fat of HFD-fed mice was decreased in comparison with non-obese mice (Figure 4D). Melatonin treatment did not show any effect but agomelatine (50 mg/kg) and metformin were able to increase its expression (Figure 4D).
Non-treated HFD-fed mice displayed a reduced expression of Ampkwhile agomelatine and metformin treatments reverted it, both in liver and fat (Figure 4D).
The flow cymetometry analysis showed that the total number of MDSCs (Ly6C+CD11b+) cells in liver was increased in obese mice compared to control mice although all treatments restored their accumulation in liver (Figure 5). Regarding the macrophages, obese mice showed a significant infiltration of CD45+CD11bint cells in liver and fat tissue. However, in the treated mice, no significant differences were observed in comparison with the lean ones. Moreover, agomelatine, at all doses, significantly reduced the number of this cell type in the liver, normalizing it, and at the highest dose the fat tissue (Figure 5).