Article Text

Download PDFPDF
NAFLD between genes and environment: what drives fibrogenesis?
  1. Angelo Armandi1,
  2. Jörn M Schattenberg2,3
  1. 1 Department of Medical Sciences, Division of Gastroenterology and Hepatology, University of Turin, Torino, Piemonte, Italy
  2. 2 Department of Medicine, University Medical Center Mainz Department of Internal Medicine 1, Mainz, Rheinland-Pfalz, Germany
  3. 3 Metabolic Liver Research Program, University Medical Center Mainz Department of Internal Medicine 1, Mainz, Rheinland-Pfalz, Germany
  1. Correspondence to Dr Jörn M Schattenberg, I. Department of Medicine, University Medical Center Mainz Department of Internal Medicine 1, 55131 Mainz, Rheinland-Pfalz, Germany; joern.schattenberg{at}unimedizin-mainz.de

Statistics from Altmetric.com

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 conclude …

View Full Text

Footnotes

  • Twitter @schattenbergj

  • AA and JMS contributed equally.

  • Contributors AA and JMS contirbuted equally.

  • Funding JMS is partly funded by the European Union Innovative Medicines Initiative 2 (IMI2) Joint Undertaking under grant agreement 777377: LITMUS (Liver Investigation: Testing Biomarker Utility in Steatohepatitis)

  • Competing interests JMS has received personal fees for consultancy to BMS, Echosens, Genfit, Gilead Sciences, Intercept Pharmaceuticals, Madrigal, Novartis, Pfizer, Roche and Siemens Healthineers.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; internally peer reviewed.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles

  • Hepatology
    Veera Raghavan Thangapandi Oskar Knittelfelder Mario Brosch Eleonora Patsenker Olga Vvedenskaya Stephan Buch Sebastian Hinz Alexander Hendricks Marina Nati Alexander Herrmann Devavrat Ravindra Rekhade Thomas Berg Madlen Matz-Soja Klaus Huse Edda Klipp Josch K Pauling Judith AH Wodke Jacobo Miranda Ackerman Malte von Bonin Elmar Aigner Christian Datz Witigo von Schönfels Sophie Nehring Sebastian Zeissig Christoph Röcken Andreas Dahl Triantafyllos Chavakis Felix Stickel Andrej Shevchenko Clemens Schafmayer Jochen Hampe Pallavi Subramanian