Globular CTRP9 inhibits oxLDL-induced inflammatory response in RAW 264.7 macrophages via AMPK activation.

C1q-TNF-related protein-9 (CTRP9) is increasingly recognized as a promising cardioprotective adipocytokine, which regulates biological processes like vascular relaxation, proliferation, apoptosis, and inflammation. We recently showed that CTRP9 enhanced carotid plaque stability by reducing pro-inflammatory cytokines in macrophages. However, the underlying molecular mechanism of CTRP9 on anti-inflammatory response in macrophages still remains unclear. We demonstrated that globular CTRP9 (gCTRP9) significantly reduced oxidized low-density lipoprotein (oxLDL)-induced tumor necrosis factor alpha and monocyte chemoattractant protein 1 expression by suppressing nuclear factor-κB phosphorylation and nuclear translocation in RAW 264.7 macrophages. Treatment with gCTRP9 strikingly increased the level of phosphorylated adenosine monophosphate-activated protein kinase (AMPK). AMPK inhibitor abolished the anti-inflammatory effects of gCTRP9. Moreover, gCTRP9 increased the expression of adiponectin receptor 1 (AdipoR1). Downregulation of AdipoR1 by siRNA could abrogate the activation of AMPK and the anti-inflammatory effects of gCTRP9. These results suggested that gCTRP9 protected RAW 264.7 macrophages from oxLDL via AMPK activation in an AdipoR1 dependent fashion.