Obesity-linked suppression of membrane-bound < i > O < /i > -Acyltransferase 7 (MBOAT7) drives non-alcoholic fatty liver disease

Recent studies have identified a genetic variant rs641738 near two genes encoding membrane boundO-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 thatMBOAT7 loss of function promotes liver disease progression1-7, but this has never been formally tested. Here we show thatMboat7 loss, but notTmc4, 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 anMboat7-dependent manner. These studies reveal a novel role for MBOAT7-driven acylation of LPI lipids in suppressing the progression of NAFLD.
Source: eLife - Category: Biomedical Science Tags: Human Biology and Medicine Source Type: research