Vanadium(IV)-chlorodipicolinate inhibits 3T3-L1 preadipocyte adipogenesis by activating LKB1/AMPK signaling pathway

Highlight•Vanadium(IV) complex with 4-chlorodipicolinic acid (VOdipic-Cl) inhibits lipid storage.•VOdipic-Cl regulates the transcriptional factors and their downstream lipogenic proteins.•VOdipic-Cl activates liver kinase B1 AMP-activated protein kinase 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 8 days. 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 2.5 μM to 10 μM 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.

Graphical abstractVanadium(IV) complex with 4-chlorodipicolinic acid (VOdipic-Cl) inhibits 3T3-L1 preadipocyte differentiation and adipogenesis by regulating the transcriptional factors and their downstream lipogenic targets via the activation of liver kinase B1 (LKB1)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathway.Figure optionsDownload full-size imageDownload as PowerPoint slide