| First Author | Gao M | Year | 2020 |
| Journal | Hum Mol Genet | Volume | 29 |
| Issue | 3 | Pages | 432-443 |
| PubMed ID | 31873720 | Mgi Jnum | J:288248 |
| Mgi Id | MGI:6416631 | Doi | 10.1093/hmg/ddz300 |
| Citation | Gao M, et al. (2020) GPAT3 deficiency alleviates insulin resistance and hepatic steatosis in a mouse model of severe congenital generalized lipodystrophy. Hum Mol Genet 29(3):432-443 |
| abstractText | Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is the most severe form of human lipodystrophy and is caused by loss-of-function mutations in the BSCL2/seipin gene. Exactly how seipin may regulate adipogenesis remains unclear. A recent study in vitro suggested that seipin may function to inhibit the activity of glycerol-3-phosphate acyltransferases (GPATs), and increased GPAT activity may be responsible for the defective adipogenesis under seipin deficiency. Here we generated Seipin-/-Gpat3-/- mice, which had mild but significant recovery of white adipose tissue mass over Seipin-/- mice. The mass of brown adipose tissue (BAT) of the Seipin-/-Gpat3-/- mice was almost completely restored to normal level. Importantly, the Seipin-/-Gpat3-/- mice showed significant improvement in liver steatosis and insulin sensitivity over Seipin-/- mice, which is attributable to the increased BAT mass and to the enhanced browning of the subcutaneous fat of the Seipin-/-Gpat3-/- mice. Together, our results establish a functional link between seipin and GPAT3 in vivo and suggest that GPAT inhibitors may have beneficial effects on BSCL2 patients. |
