3.1. Agomelatine reduces body weight and ameliorates the
altered plasma biochemical profile in HFD-fed mice.
The administration of agomelatine (10, 25 and 50 mg/kg) to HFD-fed mice
significantly lessened body weight gain compared to untreated control
obese mice (Figure 2A). Agomelatine did not present an anorexigenic
effect since it did not modify the total energy intake but lowered the
energy efficiency (Figure 2B) and consequently reduced epididymal and
abdominal fat deposits (Figure 2C). Similar effects were seen in obese
mice treated with melatonin (15 mg/kg) or metformin (250 mg/kg) (Figure
2A-C).
Mice receiving agomelatine also showed lower plasma glucose
concentrations at all time points compared to untreated HFD-fed control
mice (Figure 3A), thus resulting in significant reductions in the area
under the curve (AUC) (Figure 3A). Accordingly, these mice displayed
significantly reduced values of the HOMA-IR index (Figure 3B), a marker
of insulin intolerance calculated with the fasting insulin (Figure 3B)
and glucose values (Figure 3B)\sout. In fact, the mice treated with 50
mg/kg of agomelatine showed similar HOMA-IR index to control mice.
Likewise, melatonin and metformin ameliorated the glucose intolerance
status (Figure 3B).
Regarding the lipid profile, the untreated HFD-fed group presented a
hypercholesterolemic status, with higher levels of total cholesterol,
LDL- and HDL-cholesterol than control diet fed mice. As expected,
metformin treatment significantly ameliorated the alterations in the
cholesterol profile, reducing total and LDL-cholesterol (Figure 3C).
Interestingly, agomelatine treatment significantly improved the
cholesterol profile in the same way as metformin, whereas melatonin had
no effect on LDL-cholesterol and only significantly reduced
HDL-cholesterol (Figure 3C).