WSF-P-1, a novel AMPK activator, promotes adiponectin multimerization in 3T3-L1 adipocytes
WSF-P-1, a novel AMPK activator, promotes adiponectin multimerization in 3T3-L1 adipocytes
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WSF-P-1 是一种新型 AMPK 激活剂，可促进 3T3-L1 脂肪细胞中的脂联素多聚化
DOI：
10.1080/09168451.2017.1336923
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发表时间：
2017
影响因子：
1.6
通讯作者：
Li Zhen
中科院分区：
文献类型：
--
作者：
Wang Yao;Zhang Yudian;Wang Yunyun;Peng Han;Rui Jian;Zhang Zhijie;Wang Shifa;Li Zhen
脂联素是一种具有胰岛素增敏作用的脂肪因子，由脂肪细胞以高、中、低分子量形式（HMW、MMW和LMW）分泌进入循环。HMW脂联素低聚物具有最有效的胰岛素增敏活性。WSF-P-1（n-甲基-1,2,3,4,5,6-六氢-1,1,5,5-四甲基- 7h -2,4α-甲基萘-7-胺）是由天然倍半萜长叶烯经化学修饰而得。我们在本研究中发现WSF-P-1在3T3-L1脂肪细胞和293T细胞中都能激活AMPK。WSF-P-1激活AMPK可促进HMW脂联素的组装，并增加3T3-L1脂肪细胞中HMW/总脂联素的比率。我们证明了Ca2+依赖性CaMKK信号通路参与了wsf - p -1诱导的AMPK激活和脂联素多聚。WSF-P-1还激活glut1介导的3T3-L1脂肪细胞的葡萄糖摄取，使其成为治疗2型糖尿病、肥胖和其他肥胖相关代谢疾病的潜在候选药物。图形摘要WSF-P-1通过Ca2+-CaMKK信号通路激活AMPK，促进3T3-L1脂肪细胞的脂联素多聚和葡萄糖摄取。
Adiponectin, an adipokine with insulin-sensitizing effect, is secreted from adipocytes into circulation as high, medium, and low molecular weight forms (HMW, MMW, and LMW). The HMW adiponectin oligomers possess the most potent insulin-sensitizing activity. WSF-P-1(N-methyl-1,2,3,4,5,6-hexahydro-1,1,5,5-tetramethyl-7H-2,4α-methanonaphthalen-7-amine) is derived from natural sesquiterpene longifolene by chemical modifications. We found that WSF-P-1 activates AMPK in both 3T3-L1 adipocytes and 293T cells in this study. Activation of AMPK by WSF-P-1 promotes the assembly of HMW adiponectin and increases the HMW/total ratio of adiponectin in 3T3-L1 adipocytes. We demonstrated that the Ca2+-dependent CaMKK signaling pathway is involved in WSF-P-1-induced AMPK activation and adiponectin multimerization. WSF-P-1 also activates GLUT1-mediated glucose uptake in 3T3-L1 adipocytes, making it a potential drug candidate for the treatment of type 2 diabetes, obesity, and other obesity-related metabolic diseases. Graphical abstract WSF-P-1 activates AMPK via the Ca2+-CaMKK signaling pathway and promotes adiponectin multimerization and glucose uptake in 3T3-L1 adipocytes.