Lipidome remodeling activities of DPA-EA in palmitic acid-stimulated HepG2 cells and the in vivo anti-obesity effect of the DPA-EA and DHA-EA mixture prepared from algae oil
Background: The nuclear receptor Nur77 has been demonstrated to play a vital role in the inflammatory response and cellular metabolisms, and its ligands exhibit efficacy in the treatment of inflammation-related diseases (e.g., improving mouse acute lung injury (ALI) and obesity. Recently, ω-3 polyun...
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1146276/full |
| _version_ | 1797857793901854720 |
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| author | Hua Fang Yin Cao Jianyu Zhang Xiumei Wang Mengyu Li Mengyu Li Zhuan Hong Zhen Wu Meijuan Fang |
| author_facet | Hua Fang Yin Cao Jianyu Zhang Xiumei Wang Mengyu Li Mengyu Li Zhuan Hong Zhen Wu Meijuan Fang |
| author_sort | Hua Fang |
| collection | DOAJ |
| description | Background: The nuclear receptor Nur77 has been demonstrated to play a vital role in the inflammatory response and cellular metabolisms, and its ligands exhibit efficacy in the treatment of inflammation-related diseases (e.g., improving mouse acute lung injury (ALI) and obesity. Recently, ω-3 polyunsaturated fatty acid-ethanolamine derivatives (ω-3 PUFA-EAs), including DPA-EA and DHA-EA, have been reported as new Nur77-targeting anti-inflammatory agents. However, the lipid-lowering effect of ω-3 PUFA-EAs is still unknown, and lipid profile changes induced by Nur77-targeting anti-inflammatory agents also remain unclear.Objective: This study aimed to evaluate the lipid-lowering effect and the underlying mechanism of DPA-EA acting as Nur77-targeting anti-inflammatory agents. It also aimed to investigate the in vitro and in vivo lipid-lowering effects of the DPA-EA and DHA-EA mixture prepared from algae oil.Methods: The in vitro lipid-lowing effect of DPA-EA and its mixture with DHA-EA was first evaluated in palmitic acid-stimulated HepG2 Cells. To confirm the lipid-lowering effect and explore the underlying mechanism, we performed untargeted lipidomic analysis using ultra-performance liquid chromatography/triple quadrupole-time-of-flight (TOF) mass spectrometry coupled with multivariate statistical analysis, with another Nur77-targeting anti-inflammatory compound Celastrol (Cel) as a reference. Finally, we examined the anti-obesity effect of the DPA-EA and DHA-EA mixture synthesized from algae oil in a high-fat diet (HFD)-fed mice model.Results: DPA-EA significantly alleviated lipid accumulation with lower toxicity than Celastrol. Nur77-targeting compounds DPA-EA and Celastrol could simultaneously reduce 14 lipids (9 TGs, 2 PCs, 1 PA, 1 SM, and 1 LacCer) and increase 13 lipids (4 DGs, 6 LPEs, 2 PEs, and 1PC) in Pal-stimulated HepG2 cells. However, Cer lipids were more sensitive to DPA-EA, while the over-downregulation of SM lipids might be associated with the off-target toxicity of Celastrol. The mixture of DPA-EA and DHA-EA synthesized from algae oil could significantly decrease TG, TC, and LDL levels and increase HDL levels in HFD-fed mice, exerting an excellent anti-obesity effect.Conclusion: Nur77-targeting anti-inflammatory compound DAP-EA could promote the hydrolysis of PEs and TGs to ameliorate lipid accumulation. The DPA-EA and DHA-EA mixture prepared from algae oil might be a potential therapeutic agent for obesity and other inflammation-related diseases. |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-09T21:02:34Z |
| publishDate | 2023-03-01 |
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| spelling | doaj.art-081bc30998184bde9814d26611eedfdb2023-03-29T05:30:37ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-03-011410.3389/fphar.2023.11462761146276Lipidome remodeling activities of DPA-EA in palmitic acid-stimulated HepG2 cells and the in vivo anti-obesity effect of the DPA-EA and DHA-EA mixture prepared from algae oilHua Fang0Yin Cao1Jianyu Zhang2Xiumei Wang3Mengyu Li4Mengyu Li5Zhuan Hong6Zhen Wu7Meijuan Fang8Technical Innovation Center for Utilization of Marine Biological Resources, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen, ChinaFujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, ChinaFujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, ChinaFujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, ChinaTechnical Innovation Center for Utilization of Marine Biological Resources, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen, ChinaCollege of Ocean Food and Biological Engineering, Jimei University, Xiamen, ChinaTechnical Innovation Center for Utilization of Marine Biological Resources, Third Institute of Oceanography, Ministry of Natural Resources, Xiamen, ChinaFujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, ChinaFujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, ChinaBackground: The nuclear receptor Nur77 has been demonstrated to play a vital role in the inflammatory response and cellular metabolisms, and its ligands exhibit efficacy in the treatment of inflammation-related diseases (e.g., improving mouse acute lung injury (ALI) and obesity. Recently, ω-3 polyunsaturated fatty acid-ethanolamine derivatives (ω-3 PUFA-EAs), including DPA-EA and DHA-EA, have been reported as new Nur77-targeting anti-inflammatory agents. However, the lipid-lowering effect of ω-3 PUFA-EAs is still unknown, and lipid profile changes induced by Nur77-targeting anti-inflammatory agents also remain unclear.Objective: This study aimed to evaluate the lipid-lowering effect and the underlying mechanism of DPA-EA acting as Nur77-targeting anti-inflammatory agents. It also aimed to investigate the in vitro and in vivo lipid-lowering effects of the DPA-EA and DHA-EA mixture prepared from algae oil.Methods: The in vitro lipid-lowing effect of DPA-EA and its mixture with DHA-EA was first evaluated in palmitic acid-stimulated HepG2 Cells. To confirm the lipid-lowering effect and explore the underlying mechanism, we performed untargeted lipidomic analysis using ultra-performance liquid chromatography/triple quadrupole-time-of-flight (TOF) mass spectrometry coupled with multivariate statistical analysis, with another Nur77-targeting anti-inflammatory compound Celastrol (Cel) as a reference. Finally, we examined the anti-obesity effect of the DPA-EA and DHA-EA mixture synthesized from algae oil in a high-fat diet (HFD)-fed mice model.Results: DPA-EA significantly alleviated lipid accumulation with lower toxicity than Celastrol. Nur77-targeting compounds DPA-EA and Celastrol could simultaneously reduce 14 lipids (9 TGs, 2 PCs, 1 PA, 1 SM, and 1 LacCer) and increase 13 lipids (4 DGs, 6 LPEs, 2 PEs, and 1PC) in Pal-stimulated HepG2 cells. However, Cer lipids were more sensitive to DPA-EA, while the over-downregulation of SM lipids might be associated with the off-target toxicity of Celastrol. The mixture of DPA-EA and DHA-EA synthesized from algae oil could significantly decrease TG, TC, and LDL levels and increase HDL levels in HFD-fed mice, exerting an excellent anti-obesity effect.Conclusion: Nur77-targeting anti-inflammatory compound DAP-EA could promote the hydrolysis of PEs and TGs to ameliorate lipid accumulation. The DPA-EA and DHA-EA mixture prepared from algae oil might be a potential therapeutic agent for obesity and other inflammation-related diseases.https://www.frontiersin.org/articles/10.3389/fphar.2023.1146276/fullDPA-EAlipidomicsanti-inflammationanti-obesitybiomarker |
| spellingShingle | Hua Fang Yin Cao Jianyu Zhang Xiumei Wang Mengyu Li Mengyu Li Zhuan Hong Zhen Wu Meijuan Fang Lipidome remodeling activities of DPA-EA in palmitic acid-stimulated HepG2 cells and the in vivo anti-obesity effect of the DPA-EA and DHA-EA mixture prepared from algae oil Frontiers in Pharmacology DPA-EA lipidomics anti-inflammation anti-obesity biomarker |
| title | Lipidome remodeling activities of DPA-EA in palmitic acid-stimulated HepG2 cells and the in vivo anti-obesity effect of the DPA-EA and DHA-EA mixture prepared from algae oil |
| title_full | Lipidome remodeling activities of DPA-EA in palmitic acid-stimulated HepG2 cells and the in vivo anti-obesity effect of the DPA-EA and DHA-EA mixture prepared from algae oil |
| title_fullStr | Lipidome remodeling activities of DPA-EA in palmitic acid-stimulated HepG2 cells and the in vivo anti-obesity effect of the DPA-EA and DHA-EA mixture prepared from algae oil |
| title_full_unstemmed | Lipidome remodeling activities of DPA-EA in palmitic acid-stimulated HepG2 cells and the in vivo anti-obesity effect of the DPA-EA and DHA-EA mixture prepared from algae oil |
| title_short | Lipidome remodeling activities of DPA-EA in palmitic acid-stimulated HepG2 cells and the in vivo anti-obesity effect of the DPA-EA and DHA-EA mixture prepared from algae oil |
| title_sort | lipidome remodeling activities of dpa ea in palmitic acid stimulated hepg2 cells and the in vivo anti obesity effect of the dpa ea and dha ea mixture prepared from algae oil |
| topic | DPA-EA lipidomics anti-inflammation anti-obesity biomarker |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1146276/full |
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