| First Author | Xia M | Year | 2021 |
| Journal | J Lipid Res | Volume | 62 |
| Pages | 100031 | PubMed ID | 32859645 |
| Mgi Jnum | J:334160 | Mgi Id | MGI:6790171 |
| Doi | 10.1194/jlr.RA120000856 | Citation | Xia M, et al. (2021) Hepatic deletion of Mboat7 (LPIAT1) causes activation of SREBP-1c and fatty liver. J Lipid Res 62:100031 |
| abstractText | Genetic variants that increase the risk of fatty liver disease and cirrhosis have recently been identified in the proximity of membrane-bound O-acyltransferase domain-containing 7 (MBOAT7). To elucidate the link between these variants and fatty liver disease, we characterized Mboat7 liver-specific KO mice (Mboat7 LSKO). Chow-fed Mboat7 LSKO mice developed fatty livers and associated liver injury. Lipidomic analysis of liver using MS revealed a pronounced reduction in 20-carbon PUFA content in phosphatidylinositols (PIs) but not in other phospholipids. The change in fatty acid composition of PIs in these mice was associated with a marked increase in de novo lipogenesis because of activation of SREBP-1c, a transcription factor that coordinates the activation of genes encoding enzymes in the fatty acid biosynthesis pathway. Hepatic removal of both SREBP cleavage-activating protein (Scap) and Mboat7 normalized hepatic triglycerides relative to Scap-only hepatic KO, showing that increased SREBP-1c processing is required for Mboat7-induced steatosis. This study reveals a clear relationship between PI fatty acid composition and regulation of hepatic fat synthesis and delineates the mechanism by which mutations in MBOAT7 cause hepatic steatosis. |
