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- Title
GIRK2 potassium channels expressed by the AgRP neurons decrease adiposity and body weight in mice.
- Authors
Oh, Youjin; Yoo, Eun-Seon; Ju, Sang Hyeon; Kim, Eunha; Lee, Seulgi; Kim, Seyun; Wickman, Kevin; Sohn, Jong-Woo
- Abstract
It is well known that the neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons increase appetite and decrease thermogenesis. Previous studies demonstrated that optogenetic and/or chemogenetic manipulations of NPY/AgRP neuronal activity alter food intake and/or energy expenditure (EE). However, little is known about intrinsic molecules regulating NPY/AgRP neuronal excitability to affect long-term metabolic function. Here, we found that the G protein-gated inwardly rectifying K+ (GIRK) channels are key to stabilize NPY/AgRP neurons and that NPY/AgRP neuron-selective deletion of the GIRK2 subunit results in a persistently increased excitability of the NPY/AgRP neurons. Interestingly, increased body weight and adiposity observed in the NPY/AgRP neuron-selective GIRK2 knockout mice were due to decreased sympathetic activity and EE, while food intake remained unchanged. The conditional knockout mice also showed compromised adaptation to coldness. In summary, our study identified GIRK2 as a key determinant of NPY/AgRP neuronal excitability and driver of EE in physiological and stress conditions. It is known that a subset of neurons in the hypothalamus increase appetite and decrease thermogenesis. This study shows that the ion channel GIRK2 functions in hypothalamic NPY/AgRP neurons to increase energy expenditure in mice; activity of this ion channel may help to keep body weight under control.
- Subjects
HYPOTHALAMUS; BODY weight; POTASSIUM channels; OBESITY; NEURONS; NEUROPEPTIDE Y; REGULATION of body weight; ION channels
- Publication
PLoS Biology, 2023, Vol 21, Issue 8, p1
- ISSN
1544-9173
- Publication type
Article
- DOI
10.1371/journal.pbio.3002252