L-leucine in the fluid surrounding brain cells can directly change the activity of specific neurons in the hypothalamus, without needing to enter the cells or be processed inside them.
Mechanism
Synthesis from 1 study
L-leucine outside brain cells directly opens or closes calcium channels on the cell surface, making some neurons more active and others less active. This changes hunger signals without the molecule ever entering the cell or being broken down.
Most probable mechanism
L-leucine in the fluid around brain cells binds to special channels on the cell surface, causing calcium to flow into some neurons and out of others. This changes their electrical activity: one group becomes more active and signals fullness, while another group becomes less active and stops signaling hunger. This happens without leucine entering the cells or being broken down.
Extracellular L-leucine binds to or modulates a plasma membrane calcium channel, triggering calcium influx into hypothalamic neurons
Increased intracellular calcium concentration depolarizes anorexigenic POMC neurons, increasing their firing rate
Extracellular L-leucine inhibits a store-operated calcium channel, reducing calcium influx into orexigenic NPY/AGRP neurons
Decreased intracellular calcium concentration hyperpolarizes NPY/AGRP neurons, suppressing their firing rate
Reduced activity in NPY/AGRP neurons decreases secretion of the orexigenic neuropeptide AGRP
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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