Contribution of adipocyte Na/K-ATPase α1/CD36 signaling induced exosome secretion in response to oxidized LDL
IntroductionAdipose tissue constantly secretes adipokines and extracellular vesicles including exosomes to crosstalk with distinct tissues and organs for whole-body homeostasis. However, dysfunctional adipose tissue under chronic inflammatory conditions such as obesity, atherosclerosis, and diabetes...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1046495/full |
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| author | Sneha S. Pillai Duane G. Pereira Jue Zhang Wenxin Huang Mirza Ahmar Beg Darcy A. Knaack Bruno de Souza Goncalves Daisy Sahoo Daisy Sahoo Daisy Sahoo Roy L. Silverstein Roy L. Silverstein Joseph I. Shapiro Komal Sodhi Yiliang Chen Yiliang Chen |
| author_facet | Sneha S. Pillai Duane G. Pereira Jue Zhang Wenxin Huang Mirza Ahmar Beg Darcy A. Knaack Bruno de Souza Goncalves Daisy Sahoo Daisy Sahoo Daisy Sahoo Roy L. Silverstein Roy L. Silverstein Joseph I. Shapiro Komal Sodhi Yiliang Chen Yiliang Chen |
| author_sort | Sneha S. Pillai |
| collection | DOAJ |
| description | IntroductionAdipose tissue constantly secretes adipokines and extracellular vesicles including exosomes to crosstalk with distinct tissues and organs for whole-body homeostasis. However, dysfunctional adipose tissue under chronic inflammatory conditions such as obesity, atherosclerosis, and diabetes shows pro-inflammatory phenotypes accompanied by oxidative stress and abnormal secretion. Nevertheless, molecular mechanisms of how adipocytes are stimulated to secrete exosomes under those conditions remain poorly understood.MethodsMouse and human in vitro cell culture models were used for performing various cellular and molecular studies on adipocytes and macrophages. Statistical analysis was performed using Student's t-test (two-tailed, unpaired, and equal variance) for comparisons between two groups or ANOVA followed by Bonferroni's multiple comparison test for comparison among more than two groups.Results and discussionIn this work, we report that CD36, a scavenger receptor for oxidized LDL, formed a signaling complex with another membrane signal transducer Na/K-ATPase in adipocytes. The atherogenic oxidized LDL induced a pro-inflammatory response in in vitro differentiated mouse and human adipocytes and also stimulated the cells to secrete more exosomes. This was largely blocked by either CD36 knockdown using siRNA or pNaKtide, a peptide inhibitor of Na/K-ATPase signaling. These results showed a critical role of the CD36/Na/K-ATPase signaling complex in oxidized LDL-induced adipocyte exosome secretion. Moreover, by co-incubation of adipocyte-derived exosomes with macrophages, we demonstrated that oxidized LDL-induced adipocyte-derived exosomes promoted pro-atherogenic phenotypes in macrophages, including CD36 upregulation, IL-6 secretion, metabolic switch to glycolysis, and mitochondrial ROS production. Altogether, we show here a novel mechanism through which adipocytes increase exosome secretion in response to oxidized LDL and that the secreted exosomes can crosstalk with macrophages, which may contribute to atherogenesis. |
| first_indexed | 2024-04-09T15:44:37Z |
| format | Article |
| id | doaj.art-d1579c982def411397a95f456bf04513 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-04-09T15:44:37Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-d1579c982def411397a95f456bf045132023-04-27T05:21:12ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-04-011010.3389/fcvm.2023.10464951046495Contribution of adipocyte Na/K-ATPase α1/CD36 signaling induced exosome secretion in response to oxidized LDLSneha S. Pillai0Duane G. Pereira1Jue Zhang2Wenxin Huang3Mirza Ahmar Beg4Darcy A. Knaack5Bruno de Souza Goncalves6Daisy Sahoo7Daisy Sahoo8Daisy Sahoo9Roy L. Silverstein10Roy L. Silverstein11Joseph I. Shapiro12Komal Sodhi13Yiliang Chen14Yiliang Chen15Department of Surgery, Biomedical Sciences, and Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, United StatesDepartment of Surgery, Biomedical Sciences, and Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, United StatesVersiti Blood Research Institute, Milwaukee, WI, United StatesVersiti Blood Research Institute, Milwaukee, WI, United StatesVersiti Blood Research Institute, Milwaukee, WI, United StatesDepartment of Biochemistry, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Surgery, Biomedical Sciences, and Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, United StatesDepartment of Biochemistry, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Medicine, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, WI, United StatesVersiti Blood Research Institute, Milwaukee, WI, United StatesDepartment of Medicine, Medical College of Wisconsin, Milwaukee, WI, United StatesDepartment of Surgery, Biomedical Sciences, and Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, United StatesDepartment of Surgery, Biomedical Sciences, and Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, United StatesVersiti Blood Research Institute, Milwaukee, WI, United StatesDepartment of Medicine, Medical College of Wisconsin, Milwaukee, WI, United StatesIntroductionAdipose tissue constantly secretes adipokines and extracellular vesicles including exosomes to crosstalk with distinct tissues and organs for whole-body homeostasis. However, dysfunctional adipose tissue under chronic inflammatory conditions such as obesity, atherosclerosis, and diabetes shows pro-inflammatory phenotypes accompanied by oxidative stress and abnormal secretion. Nevertheless, molecular mechanisms of how adipocytes are stimulated to secrete exosomes under those conditions remain poorly understood.MethodsMouse and human in vitro cell culture models were used for performing various cellular and molecular studies on adipocytes and macrophages. Statistical analysis was performed using Student's t-test (two-tailed, unpaired, and equal variance) for comparisons between two groups or ANOVA followed by Bonferroni's multiple comparison test for comparison among more than two groups.Results and discussionIn this work, we report that CD36, a scavenger receptor for oxidized LDL, formed a signaling complex with another membrane signal transducer Na/K-ATPase in adipocytes. The atherogenic oxidized LDL induced a pro-inflammatory response in in vitro differentiated mouse and human adipocytes and also stimulated the cells to secrete more exosomes. This was largely blocked by either CD36 knockdown using siRNA or pNaKtide, a peptide inhibitor of Na/K-ATPase signaling. These results showed a critical role of the CD36/Na/K-ATPase signaling complex in oxidized LDL-induced adipocyte exosome secretion. Moreover, by co-incubation of adipocyte-derived exosomes with macrophages, we demonstrated that oxidized LDL-induced adipocyte-derived exosomes promoted pro-atherogenic phenotypes in macrophages, including CD36 upregulation, IL-6 secretion, metabolic switch to glycolysis, and mitochondrial ROS production. Altogether, we show here a novel mechanism through which adipocytes increase exosome secretion in response to oxidized LDL and that the secreted exosomes can crosstalk with macrophages, which may contribute to atherogenesis.https://www.frontiersin.org/articles/10.3389/fcvm.2023.1046495/fullNa/K-ATPaseCD36adipocyteexosomesoxLDLmitochondria |
| spellingShingle | Sneha S. Pillai Duane G. Pereira Jue Zhang Wenxin Huang Mirza Ahmar Beg Darcy A. Knaack Bruno de Souza Goncalves Daisy Sahoo Daisy Sahoo Daisy Sahoo Roy L. Silverstein Roy L. Silverstein Joseph I. Shapiro Komal Sodhi Yiliang Chen Yiliang Chen Contribution of adipocyte Na/K-ATPase α1/CD36 signaling induced exosome secretion in response to oxidized LDL Frontiers in Cardiovascular Medicine Na/K-ATPase CD36 adipocyte exosomes oxLDL mitochondria |
| title | Contribution of adipocyte Na/K-ATPase α1/CD36 signaling induced exosome secretion in response to oxidized LDL |
| title_full | Contribution of adipocyte Na/K-ATPase α1/CD36 signaling induced exosome secretion in response to oxidized LDL |
| title_fullStr | Contribution of adipocyte Na/K-ATPase α1/CD36 signaling induced exosome secretion in response to oxidized LDL |
| title_full_unstemmed | Contribution of adipocyte Na/K-ATPase α1/CD36 signaling induced exosome secretion in response to oxidized LDL |
| title_short | Contribution of adipocyte Na/K-ATPase α1/CD36 signaling induced exosome secretion in response to oxidized LDL |
| title_sort | contribution of adipocyte na k atpase α1 cd36 signaling induced exosome secretion in response to oxidized ldl |
| topic | Na/K-ATPase CD36 adipocyte exosomes oxLDL mitochondria |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1046495/full |
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