Hepatic deletion of Mboat7 (LPIAT1) causes activation of SREBP-1c and fatty liver

Mingfeng Xia, Preethi Chandrasekaran, Shunxing Rong, Xiaorong Fu, Matthew A. Mitsche

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Genetic variants that increase the risk of fatty liver disease and cirrhosis have recently been identified in the proximity of membrane-bound Oacyltransferase 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.

Original languageEnglish (US)
Article number100031
JournalJournal of lipid research
StatePublished - 2021


  • Fatty liver disease
  • Flux analysis
  • Lipidomics
  • Liver-specific knockout
  • Lysophosphatidylinositol acyltransferase 1
  • Membrane-bound O-acyltransferase domain-containing 7
  • Obesity
  • Phosphatidylinositol
  • Sterol regulatory element-binding protein 1c

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology


Dive into the research topics of 'Hepatic deletion of Mboat7 (LPIAT1) causes activation of SREBP-1c and fatty liver'. Together they form a unique fingerprint.

Cite this