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Updated: Sep 21, 2025

Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes
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Membrane-bound O-acyltransferase 7 (MBOAT7)-driven phosphatidylinositol remodeling in advanced liver disease

Venkateshwari Varadharajan1, William J Massey1, J Mark Brown1

  • 1Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.

Journal of Lipid Research
|May 31, 2022
PubMed

Insights

A common genetic variant near the MBOAT7 gene is linked to severe liver diseases, including nonalcoholic fatty liver disease and cirrhosis. This variant reduces MBOAT7 expression, impacting liver health and disease progression.

Area of Science:

  • Hepatology
  • Genetics
  • Molecular Biology

Background:

  • Advanced liver diseases cause millions of deaths globally, often from cirrhosis, viral hepatitis, and hepatocellular carcinoma.
  • Developing effective treatments is challenging due to limited understanding of disease mechanisms and lack of human-relevant models.
  • Genome-wide association studies identified a single nucleotide polymorphism (SNP) near the MBOAT7 gene associated with severe liver conditions.

Purpose of the Study:

  • To review recent findings on the role of MBOAT7 in liver disease.
  • To explore the mechanistic link between MBOAT7-driven phosphatidylinositol remodeling and liver disease progression.
  • To discuss the implications for future drug discovery in advanced liver diseases.

Main Methods:

  • Review of recent scientific literature and genome-wide association studies.
  • Analysis of genetic associations between MBOAT7 variants and liver disease susceptibility.
  • Examination of preclinical studies in mouse models investigating Mboat7 loss of function.

Main Results:

  • A common MBOAT7 variant (rs641738, C>T) reduces MBOAT7 expression and increases susceptibility to nonalcoholic fatty liver disease, alcohol-associated liver disease, and viral hepatitis-associated fibrosis.
  • Loss of Mboat7 function in mice promotes hepatic steatosis, inflammation, and fibrosis.
  • MBOAT7 is causally linked to liver health in both rodents and humans through phosphatidylinositol remodeling.

Conclusions:

  • MBOAT7 plays a critical role in maintaining liver health, and its reduced expression is a risk factor for various severe liver diseases.
  • Understanding MBOAT7's function in phosphatidylinositol remodeling offers new mechanistic insights into liver disease pathogenesis.
  • Targeting MBOAT7 or related pathways presents a promising avenue for developing novel therapeutic strategies for advanced liver diseases.
Keywords:
alcohol-associated liver diseasediabetesfatty liverfibrosisnonalcoholic fatty liver diseaseobesityphospholipid

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