Figure 1.

POMC and NPY/AgRP activation via ROS release in function of nutritional state. POMC and NPY/AgRP neurons generate opposing effects on food intake and metabolism. In the fed state, glucose, lipids, insulin, and leptin actions lead to ROS release in both type of neurons, for instance via a rise of Ca²⁺ concentration and mitochondrial dynamics. This transient increase in intracellular ROS stimulates POMC neurons activity and inhibits NPY/AgRP neurons, engendering decrease in food intake and increased energy expenditure. In the fasted state, NPY/AgRP neurons become more active, via an increase in Calcium Binding Proteins (CBPs) and UCP2 expression that respectively buffer excessive intracellular Ca²⁺ and prevent ROS release. This NPY/Agrp activation is mediated via ghrelin and stimulates food intake. In parallel, these neurons present GABAergic inhibitory synapses around POMC neurons, amplifying the orexigenic signal.