L-leucine activates specific neurons in the hypothalamus by triggering calcium entry through the cell membrane, without requiring the cell to metabolize it or use known signaling pathways like mTORC1...
Mechanism
Synthesis from 1 study
L-leucine in the blood directly turns on some brain cells that tell you to stop eating by letting calcium in from outside, while turning off other brain cells that tell you to eat by blocking calcium from entering. This happens without the brain needing to digest the leucine or use any known...
Most probable mechanism
L-leucine in the blood binds to a sensor on the surface of certain brain cells that control hunger, causing some cells to become more active by pulling calcium in from outside, while other cells become less active by blocking a different calcium channel. This changes the brain's signal to eat or stop eating, without needing to break down the leucine or use any known nutrient-sensing systems.
Extracellular L-leucine binds to an unidentified plasma membrane protein that functions as a calcium channel
Calcium enters hypothalamic neurons through this channel, increasing intracellular calcium concentration and depolarizing the cell membrane
Increased intracellular calcium activates anorexigenic POMC neurons, enhancing their firing rate and signaling to suppress appetite
Extracellular L-leucine simultaneously inhibits a store-operated calcium channel in a separate subset of hypothalamic neurons
Inhibition of this store-operated channel reduces calcium influx from outside the cell, lowering intracellular calcium concentration and hyperpolarizing the membrane
Decreased intracellular calcium in NPY/AGRP neurons suppresses vesicle exocytosis and reduces secretion of the orexigenic peptide AGRP
Reduced AGRP release diminishes activation of downstream feeding circuits, leading to decreased food intake initiation
Evidence from Studies
Supporting (1)
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Rapid sensing of l-leucine by human and murine hypothalamic neurons: Neurochemical and mechanistic insights
Contradicting (0)
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