CD226 knockout alleviates high-fat diet induced obesity by suppressing proinflammatory macrophage phenotype
Abstract Obesity is associated with chronic low-grade inflammation, contributing to an increasing prevalence of chronic metabolic diseases, such as insulin resistance, non-alcoholic fatty liver disease (NALFD), and steatohepatitis. Macrophages are the predominant immune cells in adipose tissues. Adi...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-11-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-021-03150-4 |
| _version_ | 1818433884053831680 |
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| author | Jingchang Ma Wei Hu Dongliang Zhang Jiangang Xie Chujun Duan Yitian Liu Yuling Wang Xuexue Xu Kun Cheng Boquan Jin Yuan Zhang Ran Zhuang |
| author_facet | Jingchang Ma Wei Hu Dongliang Zhang Jiangang Xie Chujun Duan Yitian Liu Yuling Wang Xuexue Xu Kun Cheng Boquan Jin Yuan Zhang Ran Zhuang |
| author_sort | Jingchang Ma |
| collection | DOAJ |
| description | Abstract Obesity is associated with chronic low-grade inflammation, contributing to an increasing prevalence of chronic metabolic diseases, such as insulin resistance, non-alcoholic fatty liver disease (NALFD), and steatohepatitis. Macrophages are the predominant immune cells in adipose tissues. Adipose tissue macrophages (ATMs) would switch to pro-inflammatory M1 state during obesity, causing local and systemic inflammation. However, the regulatory mechanism of ATMs has not yet been well described within this process. Using a high-fat diet (HFD)–induced mouse obesity model, we found that the costimulatory molecule CD226 was highly expressed on ATMs and knockout (KO) of CD226 alleviated obesity caused by HFD. Loss of CD226 reduced the accumulation of ATMs and hindered macrophage M1 polarization, with lower serum proinflammatory cytokine levels. Furthermore, deficiency of CD226 on ATMs decreased the phosphorylation levels of VAV1, AKT, and FOXO1 and thereby upregulated PPAR-γ. Further administration of PPAR-γ inhibitor restored M1 phenotype in CD226KO ATMs. In summary, loss of CD226 alleviates the HFD-induced obesity and systemic inflammation through inhibition of the accumulation and M1 polarization of ATMs in which PPAR-γ-dependent signaling pathway is involved, suggesting that CD226 may be identified as a potential molecular target for the clinical treatment of obesity. |
| first_indexed | 2024-12-14T16:28:11Z |
| format | Article |
| id | doaj.art-8f76a5da7c31451281311ca9e33151a8 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-14T16:28:11Z |
| publishDate | 2021-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-8f76a5da7c31451281311ca9e33151a82022-12-21T22:54:38ZengBMCJournal of Translational Medicine1479-58762021-11-0119111610.1186/s12967-021-03150-4CD226 knockout alleviates high-fat diet induced obesity by suppressing proinflammatory macrophage phenotypeJingchang Ma0Wei Hu1Dongliang Zhang2Jiangang Xie3Chujun Duan4Yitian Liu5Yuling Wang6Xuexue Xu7Kun Cheng8Boquan Jin9Yuan Zhang10Ran Zhuang11Department of Immunology, Fourth Military Medical UniversityDepartment of Immunology, Fourth Military Medical UniversityDepartment of Immunology, Fourth Military Medical UniversityDepartment of Immunology, Fourth Military Medical UniversityDepartment of Immunology, Fourth Military Medical UniversityDepartment of Immunology, Fourth Military Medical UniversityDepartment of Immunology, Fourth Military Medical UniversityInstitute of Medical Research, Northwestern Polytechnical UniversityDepartment of Immunology, Fourth Military Medical UniversityDepartment of Immunology, Fourth Military Medical UniversityInstitute of Medical Research, Northwestern Polytechnical UniversityDepartment of Immunology, Fourth Military Medical UniversityAbstract Obesity is associated with chronic low-grade inflammation, contributing to an increasing prevalence of chronic metabolic diseases, such as insulin resistance, non-alcoholic fatty liver disease (NALFD), and steatohepatitis. Macrophages are the predominant immune cells in adipose tissues. Adipose tissue macrophages (ATMs) would switch to pro-inflammatory M1 state during obesity, causing local and systemic inflammation. However, the regulatory mechanism of ATMs has not yet been well described within this process. Using a high-fat diet (HFD)–induced mouse obesity model, we found that the costimulatory molecule CD226 was highly expressed on ATMs and knockout (KO) of CD226 alleviated obesity caused by HFD. Loss of CD226 reduced the accumulation of ATMs and hindered macrophage M1 polarization, with lower serum proinflammatory cytokine levels. Furthermore, deficiency of CD226 on ATMs decreased the phosphorylation levels of VAV1, AKT, and FOXO1 and thereby upregulated PPAR-γ. Further administration of PPAR-γ inhibitor restored M1 phenotype in CD226KO ATMs. In summary, loss of CD226 alleviates the HFD-induced obesity and systemic inflammation through inhibition of the accumulation and M1 polarization of ATMs in which PPAR-γ-dependent signaling pathway is involved, suggesting that CD226 may be identified as a potential molecular target for the clinical treatment of obesity.https://doi.org/10.1186/s12967-021-03150-4CD226HFDObesityMacrophagePolarization |
| spellingShingle | Jingchang Ma Wei Hu Dongliang Zhang Jiangang Xie Chujun Duan Yitian Liu Yuling Wang Xuexue Xu Kun Cheng Boquan Jin Yuan Zhang Ran Zhuang CD226 knockout alleviates high-fat diet induced obesity by suppressing proinflammatory macrophage phenotype Journal of Translational Medicine CD226 HFD Obesity Macrophage Polarization |
| title | CD226 knockout alleviates high-fat diet induced obesity by suppressing proinflammatory macrophage phenotype |
| title_full | CD226 knockout alleviates high-fat diet induced obesity by suppressing proinflammatory macrophage phenotype |
| title_fullStr | CD226 knockout alleviates high-fat diet induced obesity by suppressing proinflammatory macrophage phenotype |
| title_full_unstemmed | CD226 knockout alleviates high-fat diet induced obesity by suppressing proinflammatory macrophage phenotype |
| title_short | CD226 knockout alleviates high-fat diet induced obesity by suppressing proinflammatory macrophage phenotype |
| title_sort | cd226 knockout alleviates high fat diet induced obesity by suppressing proinflammatory macrophage phenotype |
| topic | CD226 HFD Obesity Macrophage Polarization |
| url | https://doi.org/10.1186/s12967-021-03150-4 |
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