GIRK2 potassium channels expressed by the AgRP neurons decrease adiposity and body weight in mice

• DOI: 10.1371/journal.pbio.3002252
• Publication Date: 2023-08-18T17:38:20Z
• Authors: Youjin Oh; Eun-Seon Yoo; Sang Hyeon Ju; Eunha Kim; Seulgi Lee; Seyun Kim; Kevin Wickman; Jong-Woo Sohn
• Keywords: 2. Zero hunger; Mice, Knockout; Neurons; QH301-705.5; Body Weight; Mice; G Protein-Coupled Inwardly-Rectifying Potassium Channels; Animals; Agouti-Related Protein; Obesity; Biology (General); Peptides; Research Article; Adiposity

It is well known that the neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons increase appetite and decrease thermogenesis. Previous studies demonstrated optogenetic and/or chemogenetic manipulations of NPY/AgRP neuronal activity alter food intake energy expenditure (EE). However, little about intrinsic molecules regulating excitability to affect long-term metabolic function. Here, we found G protein-gated inwardly rectifying K+ (GIRK) channels are key stabilize neuron-selective deletion GIRK2 subunit results in a persistently increased neurons. Interestingly, body weight adiposity observed knockout mice were due decreased sympathetic EE, while remained unchanged. The conditional also showed compromised adaptation coldness. In summary, our study identified as determinant driver EE physiological stress conditions.