The increased plasma
free fatty acid levels due to the deregulated lipolysis in adipocytes are considered as one of the major risk factors for developing type II diabetes.
Vanadium compounds are well-known for their
antidiabetic effects both on
glucose and lipid metabolism, but the mechanisms are still not completely understood. The present study suggests a mechanism for how
vanadium compounds exert antilipolytic effects. It demonstrates that all the three
vanadium compounds,
bis(acetylacetonato)-oxovanadium(iv) (
VO(acac)2),
bis(maltolato)-oxovanadium(iv) (VO(ma)2) and
sodium metavanadate (NaVO3), attenuated basal lipolysis in 3T3L1 adipocytes in a dose- (from 100 to 400 μM for
VO(acac)2 and VO(ma)2, 1.0 to 4.0 mM for
vanadate) and time-dependent (from 0.5 to 4 h) manner using the
glycerol release as a marker of lipolysis. In addition, the three compounds inhibited lipolysis to a different extent. Among them,
VO(acac)2 (from 100 to 400 μM) exerted the most potent effect and reduced the lipolysis to ∼60-20% of control after 4 h treatment. The antilipolytic effects of
vanadium compounds were further evidenced by a decrease of the levels of phosphorylated HSL at Ser660 and phosphorylated
perilipin, which were counteracted by inhibitors of PI3K or Akt but not by an
MEK inhibitor. This indicates that though both Akt and ERK pathways are activated by the
vanadium compounds, only Akt activation contributes to the antilipolytic effect of the
vanadium compounds, without the involvement of ERK activation. We previously demonstrated that
VO(acac)2 can block cell cycle progression at the G1/S phase via a highly activated ERK signal in human
hepatoma HepG2 cells. Together with this study, we show that similar activated pathways may lead to differential
biological consequences for
cancer cells and adipocytes, indicating that
vanadium compounds may be used in the prevention and treatment of both diabetes and
cancer.