Vanadium(IV)-chlorodipicolinate inhibits 3T3-L1 preadipocyte adipogenesis by activating LKB1/AMPK signaling pathway.
Our previous studies demonstrated that vanadium(IV) complex with 4-chlorodipicolinic acid (VOdipic-Cl) alleviates lipid abnormalities in streptozotocin (STZ)-induced diabetic rats. However, the molecular mechanisms are not fully understood. In the present study, the effect of VOdipic-Cl on adipogenesis and mechanisms of action in 3T3-L1 preadipocytes were investigated. The 3T3-L1 preadipocytes were induced to differentiate in the presence or absence of VOdipic-Cl for 8days. The cells were determined for proliferation, differentiation, lipid accumulation as well as the protein expressions of molecular targets that are involved in fatty acid synthesis. The results demonstrated that VOdipic-Cl at concentrations ranging from 2.5μM to 10μM reduced the intracellular lipid content by 10%, 22% and 30% compared to control. VOdipic-Cl down-regulated the expression of peroxisome proliferator-activated receptor (PPARγ), CCAAT element binding protein a (C/EBPα), sterol regulatory element binding protein 1c (SREBP-1c), fatty acid synthase (FAS) and fatty acid-binding protein 4 (FABP4) and activated the phosphorylation of acetyl coenzyme A carboxylase (ACC), adenosine monophosphate-activated protein kinase (AMPK) and liver kinase B1 (LKB1) in a dose-dependent manner. Further studies showed that AMPK small interfering RNA (siRNA) markedly up-regulated PPARγ, C/EBPα, FAS and FABP4 expression in the presence of VOdipic-Cl, respectively. When LKB1 was silenced with siRNA, the effect of VOdipic-Cl on AMPK phosphorylation was diminished. Taken together, these results suggested that VOdipic-Cl can inhibit 3T3-L1 preadipocyte differentiation and adipogenesis through activating the LKB1/AMPK-dependent signaling pathway. These findings raise the possibility that VOdipic-Cl may be a promising therapy in treatment of obesity.
Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
Liang
L
Zhang
Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
Ying
Y
Huang
Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.
Fang
F
Liu
Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China. Electronic address: zhangfang@ucas.ac.cn.
Fang
F
Zhang
Laboratory of Environment and Health, College of Life Sciences, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China. Electronic address: dingwj@ucas.ac.cn.
Wenjun
W
Ding
D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D054890:Fatty Acid Synthase, Type I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D005786:Gene Expression Regulation; D051379:Mice; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010848:Picolinic Acids / Q000737:chemistry*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017968:Vanadium Compounds / Q000737:chemistry / Q000494:pharmacology*
C469871:4-chlorodipicolinic acid; D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; D056831:Coordination Complexes; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D047495:PPAR gamma; D010848:Picolinic Acids; D034741:RNA, Small Interfering; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D017968:Vanadium Compounds; D054890:Fatty Acid Synthase, Type I; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase
Adipocyte; Adipogenesis; LKB1/AMPK pathway; VOdipic-Cl