Macrophage CGI-58 Attenuates Inflammatory Responsiveness via Promotion of PPARγ Signaling
Background/Aims: Comparative gene identification-58 (CGI-58), an adipose triglyceride lipase (ATGL) coactivator, strongly promotes ATGL-mediated triglyceride (TG) catabolism. Beyond its function in promoting lipolysis, other features of CGI-58 have been proposed. Here, we investigated the role of CG...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2016-02-01
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| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/443027 |
| _version_ | 1818525532373909504 |
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| author | Dan Yang Haimei Chen Xu Zeng Ping Xie Xincun Wang Chang Liu |
| author_facet | Dan Yang Haimei Chen Xu Zeng Ping Xie Xincun Wang Chang Liu |
| author_sort | Dan Yang |
| collection | DOAJ |
| description | Background/Aims: Comparative gene identification-58 (CGI-58), an adipose triglyceride lipase (ATGL) coactivator, strongly promotes ATGL-mediated triglyceride (TG) catabolism. Beyond its function in promoting lipolysis, other features of CGI-58 have been proposed. Here, we investigated the role of CGI-58 in the regulation of inflammatory responsiveness in macrophages. Methods: Macrophage-specific GCI-58 transgenic mice (TG) and wild type mice (WT) were fed a high fat diet (HFD), and RAW264.7 cells were treated with lipopolysaccharide (LPS). The peroxisome proliferator-activated receptor (PPAR) signaling was detected. The inflammatory responsiveness and mitochondrial function were examined. Results: TG mice showed lower serum levels of proinflammatory cytokines and better mitochondrial function in macrophages compared with WT control. Knockdown of CGI-58 in RAW264.7 cells aggravated LPS-induced inflammation and mitochondrial dysfunction. CGI-58 overexpression and silencing in macrophages induced and inhibited PPARγ expression and activity, respectively. Most importantly, the PPARγ-specific agonist rosiglitazone significantly suppressed inflammation and mitochondrial dysfunction induced by CGI-58 deficiency. Furthermore, knockdown of PPARγ in macrophages significantly dampened the role of CGI-58 in suppression of inflammation and mitochondrial dysfunction. Interestingly, CGI-58 inhibited histone deacetylation and the recruitment of histone deacetylase (HDAC) to the PPARγ promoter. Finally, ATGL deficiency did not affect inflammatory responsiveness and PPARγ signaling in macrophages. Conclusion: These results demonstrate that macrophage CGI-58 enhances PPARγ signaling and thus suppresses inflammatory responsiveness and mitochondrial dysfunction. |
| first_indexed | 2024-12-11T06:10:19Z |
| format | Article |
| id | doaj.art-13db7da21c97481199e8b10f08a92ffc |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-11T06:10:19Z |
| publishDate | 2016-02-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-13db7da21c97481199e8b10f08a92ffc2022-12-22T01:18:09ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782016-02-0138269671310.1159/000443027443027Macrophage CGI-58 Attenuates Inflammatory Responsiveness via Promotion of PPARγ SignalingDan YangHaimei ChenXu ZengPing XieXincun WangChang LiuBackground/Aims: Comparative gene identification-58 (CGI-58), an adipose triglyceride lipase (ATGL) coactivator, strongly promotes ATGL-mediated triglyceride (TG) catabolism. Beyond its function in promoting lipolysis, other features of CGI-58 have been proposed. Here, we investigated the role of CGI-58 in the regulation of inflammatory responsiveness in macrophages. Methods: Macrophage-specific GCI-58 transgenic mice (TG) and wild type mice (WT) were fed a high fat diet (HFD), and RAW264.7 cells were treated with lipopolysaccharide (LPS). The peroxisome proliferator-activated receptor (PPAR) signaling was detected. The inflammatory responsiveness and mitochondrial function were examined. Results: TG mice showed lower serum levels of proinflammatory cytokines and better mitochondrial function in macrophages compared with WT control. Knockdown of CGI-58 in RAW264.7 cells aggravated LPS-induced inflammation and mitochondrial dysfunction. CGI-58 overexpression and silencing in macrophages induced and inhibited PPARγ expression and activity, respectively. Most importantly, the PPARγ-specific agonist rosiglitazone significantly suppressed inflammation and mitochondrial dysfunction induced by CGI-58 deficiency. Furthermore, knockdown of PPARγ in macrophages significantly dampened the role of CGI-58 in suppression of inflammation and mitochondrial dysfunction. Interestingly, CGI-58 inhibited histone deacetylation and the recruitment of histone deacetylase (HDAC) to the PPARγ promoter. Finally, ATGL deficiency did not affect inflammatory responsiveness and PPARγ signaling in macrophages. Conclusion: These results demonstrate that macrophage CGI-58 enhances PPARγ signaling and thus suppresses inflammatory responsiveness and mitochondrial dysfunction.http://www.karger.com/Article/FullText/443027CGI-58PPARsInflammationROSMitochondrial dysfunction |
| spellingShingle | Dan Yang Haimei Chen Xu Zeng Ping Xie Xincun Wang Chang Liu Macrophage CGI-58 Attenuates Inflammatory Responsiveness via Promotion of PPARγ Signaling Cellular Physiology and Biochemistry CGI-58 PPARs Inflammation ROS Mitochondrial dysfunction |
| title | Macrophage CGI-58 Attenuates Inflammatory Responsiveness via Promotion of PPARγ Signaling |
| title_full | Macrophage CGI-58 Attenuates Inflammatory Responsiveness via Promotion of PPARγ Signaling |
| title_fullStr | Macrophage CGI-58 Attenuates Inflammatory Responsiveness via Promotion of PPARγ Signaling |
| title_full_unstemmed | Macrophage CGI-58 Attenuates Inflammatory Responsiveness via Promotion of PPARγ Signaling |
| title_short | Macrophage CGI-58 Attenuates Inflammatory Responsiveness via Promotion of PPARγ Signaling |
| title_sort | macrophage cgi 58 attenuates inflammatory responsiveness via promotion of ppar 947 signaling |
| topic | CGI-58 PPARs Inflammation ROS Mitochondrial dysfunction |
| url | http://www.karger.com/Article/FullText/443027 |
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