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

作者：Ha Jong Hyeok; Jang Jaewoong; Chung Sang In; Yoon Yoosik^*

来源：International Journal of Molecular Medicine, 2016, 37(3): 816-824.

DOI：10.3892/ijmm.2016.2484

• AMP-activated protein kinase
• sterol regulatory element binding protein-1c
• 3T3-L1
• beta-hydroxyisovalerylshikonin
• adipogenesis

beta-hydroxyisovalerylshikonin (beta-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 beta-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 beta-HIVS was accompanied by the increased phosphorylation of AMPK and precursor SREBP-1c. In beta-HIVS-treated 3T3-L1 cells, AMPK was activated and phosphorylated precursor SREBP-1c, preventing the cleavage of precursor SREBP-1c to mature SREBP-1c. 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 SREBP-1c, 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 SREBP-1c 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 beta-HIVS activated AMPK, which was followed by the downregulation of mature SREBP-1c and fat-forming enzymes, leading to the inhibition of adipogenesis.

• 出版日期2016-3