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).