The control of hypothalamic ROS release involves many molecular actors such as mitochondrial dynamics, NADPH oxidase activity, synaptic plasticity, peroxisomes, endoplasmic reticulum,... At high levels that saturate buffering mechanisms, ROS may initiate cellular degeneration in either NPY/AgRP or POMC neurons, and impair energy homeostasis, resulting in pathologies such as obesity and type 2 diabetes. This evidence concerns the gene FMO5 and obesity due to melanocortin 4 receptor deficiency.