Neurons run on fat

Abstract

Neurons primarily rely on glucose-derived substrates to generate ATP, with neuronal activity driving increased glucose uptake and glycolysis 1 . However, neurons have a limited capacity to store fuel (glucose) 2 , 3 , 4 , raising a key question of how energy demands are maintained when glucose availability is scarce. A widely described mechanism is the astrocyte-to-neuron lactate shuttle (ANLS), in which astrocytes supply metabolites, including lactate, to support neuronal metabolism 5 , 6 , 7 . However, this glucose-centric framework is now being revised in light of recent studies in Nature Metabolism 8 , 9 , 10 , demonstrating that neurons can also metabolise long-chain fatty acids as an alternative fuel, providing an additional route to maintain energy production under these conditions.