L-leucine triggers similar rapid responses in appetite-regulating brain cells of humans and mice, with the same proportion of key neuron types reacting in both species.
Mechanism
Synthesis from 1 study
L-leucine in the blood quickly changes the activity of two types of brain cells that control hunger. It turns on cells that make you feel full by letting calcium in, and turns off cells that make you feel hungry by blocking calcium entry. This happens the same way in humans and mice.
Most probable mechanism
L-leucine in the blood binds to a calcium channel on the surface of certain brain cells that control hunger. This causes some cells that stop eating to become more active by letting in calcium, while other cells that drive eating become less active by blocking calcium entry. The result is a rapid shift in brain signaling that reduces hunger.
Extracellular L-leucine binds to or modulates a plasma membrane calcium channel in hypothalamic neurons
Calcium enters neurons through this channel, increasing intracellular calcium concentration and depolarizing anorexigenic POMC neurons
L-leucine simultaneously inhibits store-operated calcium channels in NPY/AGRP neurons, reducing extracellular calcium influx and lowering intracellular calcium concentration
Reduced intracellular calcium in NPY/AGRP neurons hyperpolarizes these cells, suppressing their activity and decreasing AGRP neuropeptide secretion
Increased POMC neuron activity and decreased NPY/AGRP neuron activity alter downstream signaling to reduce appetite
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)
Community contributions welcome
Gold Standard Evidence Needed
According to GRADE and EBM methodology, here is what ideal scientific evidence would look like to definitively prove or disprove this specific claim, ordered from strongest to weakest evidence.