The metabotropic glutamate receptor 5 (mGluR5) is known to modulate central reward pathways. The effect of the mGluR5 negative allosteric modulator VU0409106 (3, 7.5, or 15 mg/kg) or FLX (10 mg.kg) in regulating feeding and obesity parameters in diet-induced obese C57BL/6 mice was assessed. Food intake, body weight, inflammatory/hormonal levels, and behavioral tests were measured/performed. This evidence concerns the gene GRM5 and obesity disorder.