Exposure to the amino acid L-leucine at physiological concentrations triggers rapid changes in calcium levels within specific neurons in the hypothalamus of humans and mice, activating 25% of POMC...
Mechanism
Synthesis from 1 study
Leucine from protein directly turns on brain cells that signal fullness and turns off cells that signal hunger by changing calcium levels in each. This happens within seconds and stops eating without needing digestion or metabolism.
Most probable mechanism
When the amino acid leucine is present in the brain, it binds to special channels on the surface of certain nerve cells in the hypothalamus. In some cells, this opens a channel that lets calcium flow in, making the cells more active and signaling fullness. In other cells, it blocks a different calcium channel, reducing calcium inside and silencing the cells that drive hunger. This dual action quickly shifts the brain’s appetite balance toward stopping eating.
Extracellular L-leucine binds to a plasma membrane calcium channel, triggering calcium influx into anorexigenic POMC neurons
Increased intracellular calcium in POMC neurons causes depolarization and increased neuronal firing
Extracellular L-leucine inhibits a store-operated calcium channel in orexigenic NPY/AGRP neurons
Reduced calcium influx through store-operated channels lowers intracellular calcium in NPY/AGRP neurons, causing hyperpolarization and reduced firing
Decreased activity in NPY/AGRP neurons reduces secretion of the hunger-promoting neuropeptide AGRP
Reduced AGRP release diminishes activation of downstream feeding circuits, suppressing meal initiation and size
Evidence from Studies
Supporting (1)
Community contributions welcome
Rapid sensing of l-leucine by human and murine hypothalamic neurons: Neurochemical and mechanistic insights
Contradicting (0)
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