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Published on: March 24, 2023
Inducible nitric oxide synthase accelerates nonalcoholic fatty liver disease progression by regulating macrophage
Guiyuan Jin1,2, Xiaoying Yao1,2, Dong Liu1,3
1Medical Research Center, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, China.
Background:
Cells and tissues, such as macrophages, express inducible nitric oxide synthase (INOS) after stimulation by certain factors. INOS helps mediate the macrophage inflammatory reaction, but few studies have explored how INOS affects macrophage function in nonalcoholic fatty liver disease (NAFLD).
Objective:
This study investigated the role of INOS-mediated macrophage activity in NAFLD.
Methods:
A high-fat diet was used to establish an NAFLD mouse model. After 12 weeks, blood was collected for immune cell and lipid analyses, and liver tissues were collected for pathological analyses with hematoxylin and eosin and Oil Red O staining. Peritoneal macrophages were extracted in situ, cultured in Dulbecco's modified Eagle's medium, and stimulated with palmitic acid to mimic in vivo conditions for further assays. Real-time polymerase chain reaction, western blot analysis, and immunofluorescence were used to verify the expression of target genes or proteins.
Results:
In the NAFLD model, INOS expression in macrophages increased, and INOS knockdown significantly decreased the number of macrophages. Pathological examinations confirmed that INOS knockdown slowed NAFLD progression and macrophage infiltration during inflammation. INOS knockdown also enhanced phagocytosis and lipid transport by macrophages, and increased the expression of autophagy-related molecules in macrophages, which improved the autophagy level, promoted apoptotic cell degradation, and maintained intracellular environment homeostasis.
Conclusions:
These results indicate a correlation between INOS expression and macrophage function in NAFLD.
Insights
Inducible nitric oxide synthase (INOS) in macrophages is linked to nonalcoholic fatty liver disease (NAFLD) progression. Reducing INOS improves macrophage function, slows NAFLD, and enhances cellular homeostasis.
Area of Science:
- Cell Biology
- Immunology
- Hepatology
Background:
- Macrophages play a role in inflammatory reactions.
- Inducible nitric oxide synthase (INOS) is expressed by macrophages upon stimulation.
- The function of INOS in nonalcoholic fatty liver disease (NAFLD) remains under-explored.
Purpose of the Study:
- To investigate the role of INOS-mediated macrophage activity in NAFLD.
- To elucidate how INOS influences macrophage function during NAFLD pathogenesis.
Main Methods:
- Established a high-fat diet-induced NAFLD mouse model.
- Analyzed blood and liver tissues for pathological and cellular changes.
- Utilized cell culture and molecular techniques (qPCR, Western blot, immunofluorescence) to assess macrophage function and INOS expression.
Main Results:
- NAFLD model mice showed increased INOS expression in macrophages.
- INOS knockdown reduced macrophage infiltration, slowed NAFLD progression, and enhanced macrophage phagocytosis and lipid transport.
- INOS knockdown upregulated autophagy-related molecules, improving autophagy and promoting apoptotic cell clearance.
Conclusions:
- INOS expression is correlated with macrophage function in NAFLD.
- Targeting INOS in macrophages may represent a therapeutic strategy for NAFLD.
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