WSF-P-1, a novel AMPK activator, promotes adiponectin multimerization in 3T3-L1 adipocytes.
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.
['Wang|Yao|Y|http://orcid.org/0000-0001-8595-1611', 'Zhang|Yudian|Y|', 'Wang|Yunyun|Y|', 'Peng|Han|H|', 'Rui|Jian|J|', 'Zhang|Zhijie|Z|', 'Wang|Shifa|S|', 'Li|Zhen|Z|']
D041721:3T3-L1 Cells D055372:AMP-Activated Protein Kinases D017667:Adipocytes D052242:Adiponectin D000818:Animals D002118:Calcium D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase D002454:Cell Differentiation D004789:Enzyme Activation D020536:Enzyme Activators D005786:Gene Expression Regulation D005947:Glucose D051272:Glucose Transporter Type 1 D057809:HEK293 Cells D006801:Humans D007333:Insulin Resistance D051379:Mice D055503:Protein Multimerization D012717:Sesquiterpenes D015398:Signal Transduction
AMPK adiponectin CaMKK glucose uptake insulin sensitivity