Hypothalamic calcium channel acts as a leucine sensor controlling satiety and weight loss

It is not clear how appetite-regulating neurons sense dietary protein and control satiety and weight loss.

The researchers  in this study show that Cacna1g, which encodes the T-type voltage-gated calcium channel Cav3.1, is enriched in hypothalamic leucine-sensing neurons and mediates neuronal leucine sensing.

Cav3.1 inhibition pharmacologically or genetically prevents leucine-induced activation of pro-opiomelanocortin (POMC) neurons and abolishes the appetite- and weight-suppressive effects of high-protein feeding.  The authors demonstrate that leucine binds a hydrophobic pocket of Cav3.1 and lowers its threshold for voltage-dependent activation.

Cav3.1 activation promotes weight loss in diet-induced obese mice and potentiates responses to anorectic agents, including liraglutide.

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(26)00111-7

https://sciencemission.com/Cav3.1-is-a-neuronal-leucine-sensor