WSF-P-1, a novel AMPK activator, promotes adiponectin multimerization in 3T3-L1 adipocytes

Yao Wang; Yudian Zhang; Yunyun Wang; Han Peng; Jian Rui; Zhijie Zhang; Shifa Wang; Zhen Li

doi:10.1080/09168451.2017.1336923

WSF-P-1, a novel AMPK activator, promotes adiponectin multimerization in 3T3-L1 adipocytes

Biosci Biotechnol Biochem. 2017 Aug;81(8):1529-1535. doi: 10.1080/09168451.2017.1336923. Epub 2017 Jun 13.

Authors

Yao Wang¹, Yudian Zhang¹, Yunyun Wang², Han Peng², Jian Rui², Zhijie Zhang³, Shifa Wang^{2

4}, Zhen Li^{1

4}

Affiliations

¹ a MOE Key Laboratory of Bioinformatics , School of Life Sciences, Tsinghua University , Beijing , China.
² b College of Chemical Engineering , Nanjing Forestry University , Nanjing , Jiangsu , China.
³ c Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences , Beijing , China.
⁴ d School of Life Sciences , Tsinghua University , Beijing , China.

PMID: 28608766
DOI: 10.1080/09168451.2017.1336923

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.

Keywords: AMPK; CaMKK; adiponectin; glucose uptake; insulin sensitivity.

MeSH terms

3T3-L1 Cells
AMP-Activated Protein Kinases / genetics*
AMP-Activated Protein Kinases / metabolism
Adipocytes / cytology
Adipocytes / drug effects
Adipocytes / metabolism
Adiponectin / chemistry
Adiponectin / genetics*
Adiponectin / metabolism
Animals
Calcium / metabolism
Calcium-Calmodulin-Dependent Protein Kinase Kinase / genetics
Calcium-Calmodulin-Dependent Protein Kinase Kinase / metabolism
Cell Differentiation
Enzyme Activation / drug effects
Enzyme Activators / chemical synthesis
Enzyme Activators / pharmacology*
Gene Expression Regulation / drug effects
Glucose / metabolism
Glucose Transporter Type 1 / genetics
Glucose Transporter Type 1 / metabolism
HEK293 Cells
Humans
Insulin Resistance
Mice
Protein Multimerization / drug effects*
Sesquiterpenes / chemical synthesis
Sesquiterpenes / chemistry
Sesquiterpenes / pharmacology*
Signal Transduction

Substances

Adiponectin
Enzyme Activators
Glucose Transporter Type 1
Sesquiterpenes
Slc2a1 protein, mouse
longifolene
Calcium-Calmodulin-Dependent Protein Kinase Kinase
AMP-Activated Protein Kinases
Glucose
Calcium