Cyclic GMP-AMP Ameliorates Diet-induced Metabolic Dysregulation and Regulates Proinflammatory Responses Distinctly from STING Activation. Academic Article uri icon

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.

published proceedings

  • Sci Rep

author list (cited authors)

  • Guo, X., Shu, C., Li, H., Pei, Y. a., Woo, S., Zheng, J., ... Wu, C.

citation count

  • 14

complete list of authors

  • Guo, Xin||Shu, Chang||Li, Honggui||Pei, Ya||Woo, Shih-Lung||Zheng, Juan||Liu, Mengyang||Xu, Hang||Botchlett, Rachel||Guo, Ting||Cai, Yuli||Gao, Xinsheng||Zhou, Jing||Chen, Lu||Li, Qifu||Xiao, Xiaoqiu||Xie, Linglin||Zhang, Ke K||Ji, Jun-Yuan||Huo, Yuqing||Meng, Fanyin||Alpini, Gianfranco||Li, Pingwei||Wu, Chaodong

publication date

  • July 2017