• fatty liver
• inflammation
• genetic polymorphisms
• fibrogenesis
• hepatic fibrosis

In GUT Thangapandi et al explore the role of MBOAT7 in non-alcoholic fatty liver disease (NAFLD)-associated fibrogenesis.1 A single-nucleotide polymorphism (SNP) within the Mboat7 gene has been previously reported as a high-risk gene to develop advanced fibrosis in chronic viral-,2 and alcoholic liver disease as well as NAFLD.3 Additionally patients carrying the rs641738 variant in the MBOAT7 domain were more likely to develop HCC in non-cirrhotic NAFLD.4 Thus, the interest in this SNP remains high and the underlying mechanism could help to identify relevant pathways of liver injury and fibrogenesis.

MBOAT7 encodes for a multispanning transmembrane protein, which is involved in the hepatic phosphatidylinositol (PI) and lysoPI (LPI) metabolism. The identified human risk variant is associated with reduced synthesis of MBOAT7 protein and reduced conversion of LPI into PI, promoting LPI accumulation. The authors provide a novel murine model with hepatocyte-specific MBOAT7 deletion and add human data to characterise the mechanisms that lead to increased fibrosis in NAFLD. Hepatocyte-restricted deletion of MBOAT7 promotes hepatic steatosis even in the absence of high-fat diet (HFD) feeding. By adding HFD-induced stress, these mice developed augmented hepatic steatosis and fibrosis, importantly in the absence of relevant inflammatory cells or cytokines. Thus, the authors …