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Author Spotlight: Establishing MASLD Cell Models for Investigating Disease Mechanisms and the Lipid-Lowering Effects of Koumiss
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Statins as a Potential Treatment for Non-alcoholic Fatty Liver Disease: Target Deconvolution using Protein-protein

Ali Mahmoudi1,2, Alexandra E Butler3, Alexander N Orekhov4,5

  • 1Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Current Medicinal Chemistry
|August 30, 2023
PubMed
Abstract

Insights

Simvastatin shows the greatest impact on genes associated with non-alcoholic fatty liver disease (NAFLD) compared to other statins. This study used bioinformatics to analyze statin effects on NAFLD progression genes.

Area of Science:

  • Hepatology
  • Pharmacogenomics
  • Bioinformatics

Background:

  • Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive triglyceride accumulation in liver cells.
  • Numerous genes contribute to the development and progression of NAFLD.
  • Statins are commonly prescribed lipid-lowering drugs with potential effects on NAFLD-related genes.

Purpose of the Study:

  • To investigate the potential impact of statins on genes involved in non-alcoholic fatty liver disease (NAFLD) progression using bioinformatics.
  • To identify specific statins and their associated genes that may influence NAFLD pathogenesis.

Main Methods:

  • Utilized gene-drug and gene-disease databases to identify protein interactions between statins and NAFLD.
  • Constructed a Protein-Protein Interaction (PPI) network to identify hub genes and used Molecular Complex Detection (MCODE) for NAFLD-related gene clusters.
  • Performed KEGG pathway and Gene Ontology enrichment analyses on shared protein targets between statins and NAFLD genes.

Main Results:

  • Identified 24 shared protein targets between statins and NAFLD-related genes.
  • Enrichment analysis revealed involvement in cytokine-cytokine receptor interaction, adipocytokine, PPAR, TNF, and AMPK signaling pathways, as well as lipid metabolism and inflammatory response.
  • Simvastatin emerged as the statin most strongly associated with NAFLD-related genes and hub genes, including PPARA, SREBF1, and ADIPOQ.

Conclusions:

  • Simvastatin demonstrates the most significant association with NAFLD-related genes among the statins analyzed.
  • These findings suggest a potential therapeutic role for simvastatin in managing NAFLD through its effects on specific molecular pathways and genes.
Keywords:
KEGGNAFLDSTITCH.Statinsdatabasegene ontology

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