POMC and obesity due to melanocortin 4 receptor deficiency: In line with this, endocannabinoids release in postsynaptic neurons, led to retrograde activation of CB1 receptors in pre-synaptic glutamatergic SF1 neurons of the VMH, blocking calcium entry with subsequent inhibition of glutamatergic output and attenuation of POMC neurons activation, promoting feeding in diet-induced obesity [78] (Figure 4).