Effect of modulation of PPAR-γ activity on Kupffer cells M1/M2 polarization in the development of non-alcoholic fatty liver disease
| Autor: | Hui-Min Wu, Jing Hua, Wenjing Luo, Qi Wang, Qin-Yu Xu |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Kupffer Cells Macrophage polarization Peroxisome proliferator-activated receptor Inflammation Diet High-Fat Article 03 medical and health sciences Mice Non-alcoholic Fatty Liver Disease medicine Animals chemistry.chemical_classification Multidisciplinary Chemistry Macrophages Kupffer cell Fatty liver NF-kappa B Cell Polarity medicine.disease M2 Macrophage Lipids Cell biology Mice Inbred C57BL PPAR gamma 030104 developmental biology medicine.anatomical_structure RAW 264.7 Cells medicine.symptom Steatosis Signal transduction Protein Binding Signal Transduction |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Abnormal lipid-mediated hepatic inflammatory-immune dysfunction and chronic low grade inflammation play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Macrophage polarization is an important mechanism for the regulation of inflammatory response. Since PPAR-γ has emerged as a master regulator of macrophage polarization, we aimed to investigate the lipid-induced macrophage/Kupffer cell polarization in vivo and in vitro, and explore the association between PPAR-γ activity and macrophages M1/M2 polarization shifting. Here we showed that long-term high-fat diet increased Kupffer cells content with M1-predominant phenotype and increasing production of pro-inflammatory cytokines. Saturated fatty acids polarized Kupffer cells/macrophages to an M1-predominant phenotype while n-3 PUFA polarized Kupffer cells/macrophages to an M2 phenotype, which was associated with activation of NF-κB signal pathway and PPAR-γ respectively. Furthermore, up-regulation of PPAR-γ shifted lipid-induced macrophages polarization from M1-predominant phenotype to M2 phenotype. Macrophages polarization switch was associated with the interaction between PPAR-γ and NF-κBp65 signal pathway. Rosiglitazone restored high-fat diet-induced imblance of Kupffer cells M1/M2 polarization and alleviated hepatic steatosis as well as local pro-inflammatory response. These findings suggest that manipulation of PPAR-γ activity has the potential to balance lipid-induced M1/M2 macrophage/Kupffer cell polarization, and leading to prevent the development of NAFLD. |
| Databáze: | OpenAIRE |
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