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

Ha,Jong-Hyeok; Jang,Jaewoong; Chung,Sang-In; Yoon,Yoosik

doi:10.3892/ijmm.2016.2484

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

Authors:
- Jong-Hyeok Ha
- Jaewoong Jang
- Sang-In Chung
- Yoosik Yoon
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Affiliations: Department of Microbiology, Chung-Ang University College of Medicine, Seoul 156-756, Republic of Korea
Published online on: February 8, 2016 https://doi.org/10.3892/ijmm.2016.2484
Pages: 816-824

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Abstract

β-hydroxyisovalerylshikonin (β-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 β-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 β-HIVS was accompanied by the increased phosphorylation of AMPK and precursor SREBP‑1c. In β-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 β-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 β-HIVS activated AMPK, which was followed by the downregulation of mature SREBP‑1c and fat-forming enzymes, leading to the inhibition of adipogenesis.

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