AMPK and SREBP-1c mediate the anti-adipogenic effect of hydroxyisovalerylshikonin

Abstract

Hydroxyisovalerylshikonin (HIVS), which is a natural naphthoquinone compound, is one of the main chemicals isolated from a therapeutic plant, Lithospermum erythrorhizon. In the present study, we demonstrated that HIVS inhibited the adipogenesis of 3T3-L1 cells through AMP-activated protein kinase (AMPK)-mediated modulation of sterol regulatory element binDing protein (SREBP)1c. The anti-adipogenic effect of HIVS was accompanied by the increased phosphorylation of AMPK and precursor SREBPc. In HIVS-treated 3T3-L1 cells, AMPK was activated and phosphorylated precursor SREBP1c, preventing the cleavage of precursor SREBP1c to mature SREBP1c. Expression of the fat-forming enzymes, acetyl-CoA carboxylase (ACC)1, fatty acid synthase (FAS) and stearoyl-CoA desaturase (SCD)1, which are transcribed by mature SREBP1c, were downregulated, resulting in reduced intracellular fat accumulation. The anti-adipogenic effect of-HIVS was significantly attenuated by AMPK knockdown. Knockdown of AMPK using siRNA decreased the phosphorylation of precursor SREBP1c and increased the levels of mature SREBP. The levels of the fat-forming enzymes, ACC1, FAS and SCD1, as well as intracellular fat accumulation were also significantly increased by AMPK knockdown. These results suggest that HIVS activated AMPK, which was followed by the downregulation of mature SREBP1c and fat-forming enzymes, leaDing to the inhibition of adipogenesis.