GSE138945
MBOAT7's role in the progression of Non-alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH)
Recent studies have identified a genetic variant rs641738 near two genes encoding membrane bound O-acyltransferase domain-containing 7 (MBOAT7) and transmembrane channel-like 4 (TMC4) that associate with increased risk of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcohol-related cirrhosis, and liver fibrosis in those infected with viral hepatitis1-7. Based on hepatic expression quantitative trait loci analysis it has been suggested that MBOAT7 loss of function promotes liver disease progression1-7, but this has never been formally tested. Here we show that Mboat7 loss, but not Tmc4, in mice is sufficient to promote the progression of NAFLD in the setting of high fat diet. Mboat7 loss of function is associated with accumulation of its substrate lysophosphatidylinositol (LPI) lipids, and direct administration of LPI promotes hepatic inflammatory and fibrotic transcriptional changes in an Mboat7-dependent manner. These studies reveal a novel role for MBOAT7-driven acylation of LPI lipids in suppressing the progression of N Overall design: RNAseq of liver homogenates from high fat diet fed: MBOAT7 ASO knockdown vs MBOAT7 Control ASO mice Please note that the processed data file contains raw count data for both GSE138945 and GSE138946 samples.