The Effect of Lipopolysaccharide-Stimulated Adipose-Derived Mesenchymal Stem Cells on NAFLD Treatment in High-Fat Diet-Fed Rats

Reza Afarin; Fereshteh Aslani; Shahla Asadizade; Bahar Jaberian Asl; Mehrnoosh Mohammadi Gahrooie; Elham Shakerian; Akram Ahangarpour

doi:10.5812/ijpr-134807

The Effect of Lipopolysaccharide-Stimulated Adipose-Derived Mesenchymal Stem Cells on NAFLD Treatment in High-Fat Diet-Fed Rats

Iran J Pharm Res. 2023 Jun 24;22(1):e134807. doi: 10.5812/ijpr-134807. eCollection 2023 Jan-Dec.

Authors

Reza Afarin¹, Fereshteh Aslani¹, Shahla Asadizade¹, Bahar Jaberian Asl¹, Mehrnoosh Mohammadi Gahrooie¹, Elham Shakerian¹, Akram Ahangarpour²

Affiliations

¹ Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
² Diabetes Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Abstract

Background: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are 2 common liver diseases that currently lack effective treatment options.

Objectives: This study aimed to investigate the effect of lipopolysaccharide (LPS)-stimulated adipose-derived stem cells (ADSCs) on NAFLD treatment in an animal model.

Methods: Male Wistar rats were fed a high-fat diet (HFD) to induce NAFLD for 7 weeks. The rats were then categorized into 3 groups: Mesenchymal stem cell (MSC), MSC + LPS, and fenofibrate (FENO) groups. Liver and body weight were measured, and the expression of genes involved in fatty acid biosynthesis, β-oxidation, and inflammatory responses was assessed.

Results: Lipopolysaccharide-stimulated ADSCs were more effective in regulating liver and body weight gain and reducing liver triglyceride (TG) levels compared to the other groups. Treatment with LPS-stimulated ADSCs effectively corrected liver enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and lipid factors, including low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) values, better than treatment with both FENO and MSCs. ADSCs + LPS treatment significantly decreased transforming growth factor β (TGF-β) and genes associated with inflammatory responses. Additionally, there was a significant reduction in reactive oxygen species (ROS) levels in the rats treated with ADSCs + LPS.

Conclusions: Lipopolysaccharide-stimulated ADSCs showed potential in alleviating NAFLD by reducing inflammatory genes and ROS levels in HFD rats, demonstrating better results than treatment with ADSCs and FENO groups alone.

Keywords: ADSCs; Inflammation; Lipopolysaccharide; NAFLD/NASH; TGF-β.