Cyclic GMP-AMP Ameliorates Diet-induced Metabolic Dysregulation and Regulates Proinflammatory Responses Distinctly from STING Activation
Abstract Endogenous cyclic GMP-AMP (cGAMP) binds and activates STING to induce type I interferons. However, whether cGAMP plays any roles in regulating metabolic homeostasis remains unknown. Here we show that exogenous cGAMP ameliorates obesity-associated metabolic dysregulation and uniquely alters...
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2017
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oai:doaj.org-article:0eb94b4ac1234b1abef97562d680489e2021-12-02T16:08:19ZCyclic GMP-AMP Ameliorates Diet-induced Metabolic Dysregulation and Regulates Proinflammatory Responses Distinctly from STING Activation10.1038/s41598-017-05884-y2045-2322https://doaj.org/article/0eb94b4ac1234b1abef97562d680489e2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05884-yhttps://doaj.org/toc/2045-2322Abstract Endogenous cyclic GMP-AMP (cGAMP) binds and activates STING to induce type I interferons. However, whether cGAMP plays any roles in regulating metabolic homeostasis remains unknown. Here we show that exogenous cGAMP ameliorates obesity-associated metabolic dysregulation and uniquely alters proinflammatory responses. In obese mice, treatment with cGAMP significantly decreases diet-induced proinflammatory responses in liver and adipose tissues and ameliorates metabolic dysregulation. Strikingly, cGAMP exerts cell-type-specific anti-inflammatory effects on macrophages, hepatocytes, and adipocytes, which is distinct from the effect of STING activation by DMXAA on enhancing proinflammatory responses. While enhancing insulin-stimulated Akt phosphorylation in hepatocytes and adipocytes, cGAMP weakens the effects of glucagon on stimulating hepatocyte gluconeogenic enzyme expression and glucose output and blunts palmitate-induced hepatocyte fat deposition in an Akt-dependent manner. Taken together, these results suggest an essential role for cGAMP in linking innate immunity and metabolic homeostasis, indicating potential applications of cGAMP in treating obesity-associated inflammatory and metabolic diseases.Xin GuoChang ShuHonggui LiYa PeiShih-Lung WooJuan ZhengMengyang LiuHang XuRachel BotchlettTing GuoYuli CaiXinsheng GaoJing ZhouLu ChenQifu LiXiaoqiu XiaoLinglin XieKe K. ZhangJun-Yuan JiYuqing HuoFanyin MengGianfranco AlpiniPingwei LiChaodong WuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) |
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Medicine R Science Q Xin Guo Chang Shu Honggui Li Ya Pei Shih-Lung Woo Juan Zheng Mengyang Liu Hang Xu Rachel Botchlett Ting Guo Yuli Cai Xinsheng Gao Jing Zhou Lu Chen Qifu Li Xiaoqiu Xiao Linglin Xie Ke K. Zhang Jun-Yuan Ji Yuqing Huo Fanyin Meng Gianfranco Alpini Pingwei Li Chaodong Wu Cyclic GMP-AMP Ameliorates Diet-induced Metabolic Dysregulation and Regulates Proinflammatory Responses Distinctly from STING Activation |
| description |
Abstract Endogenous cyclic GMP-AMP (cGAMP) binds and activates STING to induce type I interferons. However, whether cGAMP plays any roles in regulating metabolic homeostasis remains unknown. Here we show that exogenous cGAMP ameliorates obesity-associated metabolic dysregulation and uniquely alters proinflammatory responses. In obese mice, treatment with cGAMP significantly decreases diet-induced proinflammatory responses in liver and adipose tissues and ameliorates metabolic dysregulation. Strikingly, cGAMP exerts cell-type-specific anti-inflammatory effects on macrophages, hepatocytes, and adipocytes, which is distinct from the effect of STING activation by DMXAA on enhancing proinflammatory responses. While enhancing insulin-stimulated Akt phosphorylation in hepatocytes and adipocytes, cGAMP weakens the effects of glucagon on stimulating hepatocyte gluconeogenic enzyme expression and glucose output and blunts palmitate-induced hepatocyte fat deposition in an Akt-dependent manner. Taken together, these results suggest an essential role for cGAMP in linking innate immunity and metabolic homeostasis, indicating potential applications of cGAMP in treating obesity-associated inflammatory and metabolic diseases. |
| format |
article |
| author |
Xin Guo Chang Shu Honggui Li Ya Pei Shih-Lung Woo Juan Zheng Mengyang Liu Hang Xu Rachel Botchlett Ting Guo Yuli Cai Xinsheng Gao Jing Zhou Lu Chen Qifu Li Xiaoqiu Xiao Linglin Xie Ke K. Zhang Jun-Yuan Ji Yuqing Huo Fanyin Meng Gianfranco Alpini Pingwei Li Chaodong Wu |
| author_facet |
Xin Guo Chang Shu Honggui Li Ya Pei Shih-Lung Woo Juan Zheng Mengyang Liu Hang Xu Rachel Botchlett Ting Guo Yuli Cai Xinsheng Gao Jing Zhou Lu Chen Qifu Li Xiaoqiu Xiao Linglin Xie Ke K. Zhang Jun-Yuan Ji Yuqing Huo Fanyin Meng Gianfranco Alpini Pingwei Li Chaodong Wu |
| author_sort |
Xin Guo |
| title |
Cyclic GMP-AMP Ameliorates Diet-induced Metabolic Dysregulation and Regulates Proinflammatory Responses Distinctly from STING Activation |
| title_short |
Cyclic GMP-AMP Ameliorates Diet-induced Metabolic Dysregulation and Regulates Proinflammatory Responses Distinctly from STING Activation |
| title_full |
Cyclic GMP-AMP Ameliorates Diet-induced Metabolic Dysregulation and Regulates Proinflammatory Responses Distinctly from STING Activation |
| title_fullStr |
Cyclic GMP-AMP Ameliorates Diet-induced Metabolic Dysregulation and Regulates Proinflammatory Responses Distinctly from STING Activation |
| title_full_unstemmed |
Cyclic GMP-AMP Ameliorates Diet-induced Metabolic Dysregulation and Regulates Proinflammatory Responses Distinctly from STING Activation |
| title_sort |
cyclic gmp-amp ameliorates diet-induced metabolic dysregulation and regulates proinflammatory responses distinctly from sting activation |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/0eb94b4ac1234b1abef97562d680489e |
| work_keys_str_mv |
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