دورية أكاديمية
Cyclic GMP-AMP Ameliorates Diet-induced Metabolic Dysregulation and Regulates Proinflammatory Responses Distinctly from STING Activation
| العنوان: | Cyclic GMP-AMP Ameliorates Diet-induced Metabolic Dysregulation and Regulates Proinflammatory Responses Distinctly from STING Activation |
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| المؤلفون: | 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 |
| المصدر: | Scientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) |
| بيانات النشر: | Nature Portfolio, 2017. |
| سنة النشر: | 2017 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-017-05884-y |
| URL الوصول: | https://doaj.org/article/0eb94b4ac1234b1abef97562d680489e |
| رقم الأكسشن: | edsdoj.0eb94b4ac1234b1abef97562d680489e |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-017-05884-y |