Adiponectin is an adipocyte-derived cytokine that exerts antidiabetic and anti-atherogenic properties and has been shown to enhance insulin sensitivity and promote lipid metabolism in obesity-linked diseases through the anti-inflammatory action. However, the detail mechanism of the anti-inflammatory effect of adiponectin remains unknown. In the present study, we found that in 50 patients with newly diagnosed type 2 diabetes (T2D), the circulating levels of adiponectin correlate inversely with IL-18 (r = -0.64, P < 0.01). On this basis and in vitro, we demonstrated that adiponectin significantly attenuates IL-18 secreation from LPS+PA-induced THP-1 cells (P < 0.01). In addition, we reported here that adiponectin inhibits IL-18 by suppressing NLRP3 inflammasome activation. Importantly, we found that adiponectin suppressed LPS+PA (palmitic acid)-induced ROS production, which is required for NLRP3 inflammasome activation. Furtherly, we, for the first time, described that adiponectin attenuates NLRP3 inflammasome activation by modulating AMPK-ROS signaling pathway, as the reason that suppression of AMPK with small interfering RNA (siRNA) abolished adiponectin-mediated inhibition of ROS and NLRP3 inflammasome. In vivo studies with STZ-induced diabetic mice models, we showed that adenovirus-mediated overexpression of adiponectin decreased triglycerides and cholesterol in the serum of diabetic mice. Meanwhile, adiponectin decreased CD68 positive macrophages infiltrated in adipose tissue. Furthermore, adiponectin reduced activation of NLRP3 inflammasome in liver and white adipose tissue (WAT) with western blot assay. Taken together, we report a new mechanism that adiponectin alleviates inflammation through NLRP3 inflammasome inhibition by modulating AMPK-ROS pathway, which may have therapeutic implications for T2D and the related metabolic diseases.


F. Wang: None. L. Wang: None. Y. Liu: None. J. Yuan: None. Z. Mo: None.

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