Pnoc-flox Mouse

Pnoc, also known as prepronociceptin, is a gene that plays a crucial role in energy homeostasis and feeding regulation. It is associated with pathways related to appetite control.

PNOC-expressing neurons in the arcuate nucleus of the hypothalamus (ARC) are part of a previously unrecognized GABAergic population distinct from well-defined feeding regulatory AgRP or POMC neurons [1]. These neurons arborize densely in the ARC and provide inhibitory synaptic input to nearby anorexigenic POMC neurons, promoting hyperphagia and obesity upon high-fat-diet (HFD) feeding [1].

Selective ablation of PNOCARC neurons promotes the activation of POMC neurons upon HFD exposure, reduces feeding, and protects from obesity, but it does not affect food intake or body weight under normal chow consumption [1]. Also, loss of leptin receptor (Lepr) expression in PNOC-expressing neurons in the ARC causes hyperphagia and obesity, while restoring Lepr expression in PNOC neurons on a Lepr-null obese background substantially reduces body weight [2].

In conclusion, Pnoc is essential in regulating appetite and body weight, especially in the context of high-fat-diet-induced obesity. The study of Pnoc using gene-knockout (KO) or conditional-knockout (CKO) mouse models has revealed its key role in these processes, providing potential targets for obesity therapeutics.