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).