Triptolide exhibits anti-inflammatory effects on adipocytes and macrophages by inhibition of AMPK/mTOR pathway

Obesity is a growing global health problem and chronic over-nutrition disease with lipid accumulation that results in low-grade chronic inflammation in the microenvironment of adipose tissue. Triptolide is a diterpene lactone compound extracted from the roots of the Chinese herb TWHF and possesses a therapeutic potential due to its immunosuppressive and anti-inflammatory properties. In this study, we built obesity-related inflammatory models of adipocytes using LPS, Ma-CM and raw264.7 macrophages, while the obesity-related inflammatory models of macrophages were built using LPS and Ad-CM system. We used these inflammatory models to investigate the anti-inflammatory property of triptolide. Treatment of triptolide (0.005, 0.010, 0.020 and 0.040 μ M) inhibited LPS-induced or macrophages conditioned medium-stimulated activation of AMPK/mTOR signaling pathway (p < 0.05). The results showed that triptolide reduced the release of chemokines MCP-1, RANTES, EOTAXIN and KC in LPS, Ma-CM or RAW264.7 macrophages-stimulated 3T3-L1 adipocytes. Triptolide also diminished MCP-1, RANTES, EOTAXIN, KC and TNF-α in Ad-CM stimulated RAW264.7 macrophages, while expression of MCP-1, RANTES, TNF-α, GM-CSF and IL-6 was decreased in LPS stimulated RAW264.7 macrophages (p < 0.05). These results demonstrate that triptolide is not only effective against inflammatory response of RAW264.7 macrophages or 3T3-L1 adipocytes, but also disrupts the crosstalk between macrophages and adipocytes, particularly by inhibiting secretion of pro-inflammatory mediators through inhibiting the activation of AMPK/mTOR signaling pathway. Triptolide might benefit to ameliorate obesity-induced inflammatory diseases.