| First Author | Zhang Y | Year | 2017 |
| Journal | Nat Cell Biol | Volume | 19 |
| Issue | 5 | Pages | 504-517 |
| PubMed ID | 28436964 | Mgi Jnum | J:246515 |
| Mgi Id | MGI:5925130 | Doi | 10.1038/ncb3514 |
| Citation | Zhang Y, et al. (2017) SWELL1 is a regulator of adipocyte size, insulin signalling and glucose homeostasis. Nat Cell Biol 19(5):504-517 |
| abstractText | Adipocytes undergo considerable volumetric expansion in the setting of obesity. It has been proposed that such marked increases in adipocyte size may be sensed via adipocyte-autonomous mechanisms to mediate size-dependent intracellular signalling. Here, we show that SWELL1 (LRRC8a), a member of the Leucine-Rich Repeat Containing protein family, is an essential component of a volume-sensitive ion channel (VRAC) in adipocytes. We find that SWELL1-mediated VRAC is augmented in hypertrophic murine and human adipocytes in the setting of obesity. SWELL1 regulates adipocyte insulin-PI3K-AKT2-GLUT4 signalling, glucose uptake and lipid content via SWELL1 C-terminal leucine-rich repeat domain interactions with GRB2/Cav1. Silencing GRB2 in SWELL1 KO adipocytes rescues insulin-pAKT2 signalling. In vivo, shRNA-mediated SWELL1 knockdown and adipose-targeted SWELL1 knockout reduce adiposity and adipocyte size in obese mice while impairing systemic glycaemia and insulin sensitivity. These studies identify SWELL1 as a cell-autonomous sensor of adipocyte size that regulates adipocyte growth, insulin sensitivity and glucose tolerance. |
