The involvement of peroxisome proliferator-activated receptor gamma (PPARγ) in anti-inflammatory activity of N-stearoylethanolamine
Background: N-stearoylethanolamine (NSE) is a bioactive lipid amine with a wide range of biological activities. Anti-inflammatory properties of NSE were previously confirmed on multiple animal models. However, the molecular mechanisms of anti-inflammatory action of NSE remain unclear. In the current...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-11-01
|
| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S240584402202624X |
| _version_ | 1811320576081395712 |
|---|---|
| author | H. Kosiakova A. Berdyshev V. Dosenko T. Drevytska O. Herasymenko N. Hula |
| author_facet | H. Kosiakova A. Berdyshev V. Dosenko T. Drevytska O. Herasymenko N. Hula |
| author_sort | H. Kosiakova |
| collection | DOAJ |
| description | Background: N-stearoylethanolamine (NSE) is a bioactive lipid amine with a wide range of biological activities. Anti-inflammatory properties of NSE were previously confirmed on multiple animal models. However, the molecular mechanisms of anti-inflammatory action of NSE remain unclear. In the current study, we examined the involvement of nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) in the NF-kB –dependent pathway of anti-inflammatory action of NSE using different methodological approaches. Methods: Molecular modeling calculated the possibility of NSE binding PPAR. Ex vivo experiment, using selective agonist of PPARα/γ - LY-171883 and antagonist of PPARγ - GW9662, examined the role of PPARα/γ in the NSE’s effect on nuclear NF-kB translocation in LPS-activated rat peritoneal macrophages. Finally, the NSE’s action on mRNA level of PPARγ-dependent genes was studied in the liver of insulin-resistant rats. Results: The results of molecular docking showed that NSE could bind to PPARγ and compete for the binding site with antagonist GW9662 and agonist LY-171883. These data was supported by in vitro study where pre-treatment with NSE prevented further LPS-induced NF-kB translocation into the nuclei of rat peritoneal macrophages. NSE treatment before GW9662 and LPS addition normalized the level of NF-kB translocation and IL-1β content. This finding confirmed a competitive binding of NSE with GW9662 for the ligand-binding domain of PPARγ. Additional in vivo study showed that NSE administration changed the mRNA expression of several PPARγ target genes, including SLC27A1 encoding fatty acid transport protein-1 and IL1RN - interleukin-1 receptor antagonist in insulin resistant rats. Conclusion: NSE suppressed nuclear translocation of NF-κB in LPS-stimulated peritoneal macrophages via PPARγ and changed hepatic mRNA expression of PPARγ target genes (SLC27A1, IL1RN) in insulin resistant rats. |
| first_indexed | 2024-04-13T13:01:53Z |
| format | Article |
| id | doaj.art-59f19054a25c432c8204c2eb3384285e |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-13T13:01:53Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-59f19054a25c432c8204c2eb3384285e2022-12-22T02:45:54ZengElsevierHeliyon2405-84402022-11-01811e11336The involvement of peroxisome proliferator-activated receptor gamma (PPARγ) in anti-inflammatory activity of N-stearoylethanolamineH. Kosiakova0A. Berdyshev1V. Dosenko2T. Drevytska3O. Herasymenko4N. Hula5Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, UkrainePalladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, UkraineBogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, UkraineBogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, UkrainePalladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, Ukraine; Corresponding author.Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv, UkraineBackground: N-stearoylethanolamine (NSE) is a bioactive lipid amine with a wide range of biological activities. Anti-inflammatory properties of NSE were previously confirmed on multiple animal models. However, the molecular mechanisms of anti-inflammatory action of NSE remain unclear. In the current study, we examined the involvement of nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) in the NF-kB –dependent pathway of anti-inflammatory action of NSE using different methodological approaches. Methods: Molecular modeling calculated the possibility of NSE binding PPAR. Ex vivo experiment, using selective agonist of PPARα/γ - LY-171883 and antagonist of PPARγ - GW9662, examined the role of PPARα/γ in the NSE’s effect on nuclear NF-kB translocation in LPS-activated rat peritoneal macrophages. Finally, the NSE’s action on mRNA level of PPARγ-dependent genes was studied in the liver of insulin-resistant rats. Results: The results of molecular docking showed that NSE could bind to PPARγ and compete for the binding site with antagonist GW9662 and agonist LY-171883. These data was supported by in vitro study where pre-treatment with NSE prevented further LPS-induced NF-kB translocation into the nuclei of rat peritoneal macrophages. NSE treatment before GW9662 and LPS addition normalized the level of NF-kB translocation and IL-1β content. This finding confirmed a competitive binding of NSE with GW9662 for the ligand-binding domain of PPARγ. Additional in vivo study showed that NSE administration changed the mRNA expression of several PPARγ target genes, including SLC27A1 encoding fatty acid transport protein-1 and IL1RN - interleukin-1 receptor antagonist in insulin resistant rats. Conclusion: NSE suppressed nuclear translocation of NF-κB in LPS-stimulated peritoneal macrophages via PPARγ and changed hepatic mRNA expression of PPARγ target genes (SLC27A1, IL1RN) in insulin resistant rats.http://www.sciencedirect.com/science/article/pii/S240584402202624XN-StearoylethanolaminePPARNF-kBIL-1βInflammationInsulin resistance |
| spellingShingle | H. Kosiakova A. Berdyshev V. Dosenko T. Drevytska O. Herasymenko N. Hula The involvement of peroxisome proliferator-activated receptor gamma (PPARγ) in anti-inflammatory activity of N-stearoylethanolamine Heliyon N-Stearoylethanolamine PPAR NF-kB IL-1β Inflammation Insulin resistance |
| title | The involvement of peroxisome proliferator-activated receptor gamma (PPARγ) in anti-inflammatory activity of N-stearoylethanolamine |
| title_full | The involvement of peroxisome proliferator-activated receptor gamma (PPARγ) in anti-inflammatory activity of N-stearoylethanolamine |
| title_fullStr | The involvement of peroxisome proliferator-activated receptor gamma (PPARγ) in anti-inflammatory activity of N-stearoylethanolamine |
| title_full_unstemmed | The involvement of peroxisome proliferator-activated receptor gamma (PPARγ) in anti-inflammatory activity of N-stearoylethanolamine |
| title_short | The involvement of peroxisome proliferator-activated receptor gamma (PPARγ) in anti-inflammatory activity of N-stearoylethanolamine |
| title_sort | involvement of peroxisome proliferator activated receptor gamma pparγ in anti inflammatory activity of n stearoylethanolamine |
| topic | N-Stearoylethanolamine PPAR NF-kB IL-1β Inflammation Insulin resistance |
| url | http://www.sciencedirect.com/science/article/pii/S240584402202624X |
| work_keys_str_mv | AT hkosiakova theinvolvementofperoxisomeproliferatoractivatedreceptorgammapparginantiinflammatoryactivityofnstearoylethanolamine AT aberdyshev theinvolvementofperoxisomeproliferatoractivatedreceptorgammapparginantiinflammatoryactivityofnstearoylethanolamine AT vdosenko theinvolvementofperoxisomeproliferatoractivatedreceptorgammapparginantiinflammatoryactivityofnstearoylethanolamine AT tdrevytska theinvolvementofperoxisomeproliferatoractivatedreceptorgammapparginantiinflammatoryactivityofnstearoylethanolamine AT oherasymenko theinvolvementofperoxisomeproliferatoractivatedreceptorgammapparginantiinflammatoryactivityofnstearoylethanolamine AT nhula theinvolvementofperoxisomeproliferatoractivatedreceptorgammapparginantiinflammatoryactivityofnstearoylethanolamine AT hkosiakova involvementofperoxisomeproliferatoractivatedreceptorgammapparginantiinflammatoryactivityofnstearoylethanolamine AT aberdyshev involvementofperoxisomeproliferatoractivatedreceptorgammapparginantiinflammatoryactivityofnstearoylethanolamine AT vdosenko involvementofperoxisomeproliferatoractivatedreceptorgammapparginantiinflammatoryactivityofnstearoylethanolamine AT tdrevytska involvementofperoxisomeproliferatoractivatedreceptorgammapparginantiinflammatoryactivityofnstearoylethanolamine AT oherasymenko involvementofperoxisomeproliferatoractivatedreceptorgammapparginantiinflammatoryactivityofnstearoylethanolamine AT nhula involvementofperoxisomeproliferatoractivatedreceptorgammapparginantiinflammatoryactivityofnstearoylethanolamine |