| First Author | Jun H | Year | 2020 |
| Journal | Dev Cell | Volume | 54 |
| Issue | 1 | Pages | 106-116.e5 |
| PubMed ID | 32533922 | Mgi Jnum | J:297061 |
| Mgi Id | MGI:6471608 | Doi | 10.1016/j.devcel.2020.05.017 |
| Citation | Jun H, et al. (2020) Adrenergic-Independent Signaling via CHRNA2 Regulates Beige Fat Activation. Dev Cell 54(1):106-116.e5 |
| abstractText | Maintaining energy homeostasis upon environmental challenges, such as cold or excess calorie intake, is essential to the fitness and survival of mammals. Drug discovery efforts targeting beta-adrenergic signaling have not been fruitful after decades of intensive research. We recently identified a new beige fat regulatory pathway mediated via the nicotinic acetylcholine receptor subunit CHRNA2. Here, we generated fat-specific Chrna2 KO mice and observed thermogenic defects in cold and metabolic dysfunction upon dietary challenges caused by adipocyte-autonomous regulation in vivo. We found that CHRNA2 signaling is activated after acute high fat diet feeding and this effect is manifested through both UCP1- and creatine-mediated mechanisms. Furthermore, our data suggested that CHRNA2 signaling may activate glycolytic beige fat, a subpopulation of beige adipocytes mediated by GABPalpha emerging in the absence of beta-adrenergic signaling. These findings reveal the biological significance of the CHRNA2 pathway in beige fat biogenesis and energy homeostasis. |
