WSF-P-1, a novel AMPK activator,promotes adiponectin multimerization in 3T3-L1 adipocytes |
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| Authors: | Yao Wang Yudian Zhang Yunyun Wang Han Peng Jian Rui Zhijie Zhang |
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| Institution: | 1. MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China;2. College of Chemical Engineering, Nanjing Forestry University, Nanjing, Jiangsu, China;3. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China |
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| Abstract: | 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. |
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| Keywords: | adiponectin AMPK CaMKK insulin sensitivity glucose uptake |
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