Considering these very few and contradictory findings, our group recently analyzed hypothalamic 2-AG and AEA fluctuations at different stages of DIO in mice and evaluated, for the first time, the association of these fluctuations to brown adipose tissue (BAT) thermogenesis activation and leptin response during obesity progression [59] (Fig. 3). The gene discussed is LEP; the disease is obesity due to melanocortin 4 receptor deficiency.