GABAergic disinhibition from the BNST to PNOC neurons promotes HFD-induced hyperphagia.

Activation of prepronociceptin (PNOC)-expressing neurons in the arcuate nucleus (ARC) promotes high-fat-diet (HFD)-induced hyperphagia. In turn, PNOC neurons can inhibit the anorexic response of proopiomelanocortin (POMC) neurons. Here, we validate the necessity of PNOC activity for HFD-induced inhibition of POMC neurons in mice and find that PNOC-neuron-dependent inhibition of POMC neurons is mediated by gamma-aminobutyric acid (GABA) release.