Obesity has become an important health problem and its prevalence is highlyincreasing. Pharmacotherapy alone or in combination with either lifestylemodification or surgery, is consistent in maintaining a healthy body weight, andpreventing progression to obesity-related diseases. However, the anti-obesitydrugs are limited by non-specificity and unsustainable weight loss effects.Therefore, further research is needed to develop new preventive and treatmentapproaches against obesity. Here we targeted the brain lipid metabolism as apromising strategy. In the brain,the hypothalamus harbors specialized functional circuits in thephysiological regulation of calories intake and spend. Importantly, some enzymesinvolved in fatty acid metabolism are highly expressed in the hypothalamus. Wetook advantage of the C75-CoA, a strong competitive inhibitor of carnitinepalmitoyltransferase 1A (CPT1A) that catalyzes the rate-limiting step offatty-acid oxidation.