title: AMPK and SREBP-1c mediate the anti-adipogenic effect of β-hydroxyisovalerylshikonin.
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.
authors: Department of Microbiology, Chung-Ang University College of Medicine, Seoul 156-756, Republic of Korea.
authors: Jong-Hyeok
authors: JH
authors: Ha
authors: Department of Microbiology, Chung-Ang University College of Medicine, Seoul 156-756, Republic of Korea.
authors: Jaewoong
authors: J
authors: Jang
authors: Department of Microbiology, Chung-Ang University College of Medicine, Seoul 156-756, Republic of Korea.
authors: Sang-In
authors: SI
authors: Chung
authors: Department of Microbiology, Chung-Ang University College of Medicine, Seoul 156-756, Republic of Korea.
authors: Yoosik
authors: Y
authors: Yoon
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D051379:Mice; D009285:Naphthoquinones / Q000494:pharmacology / Q000506:poisoning*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D009285:Naphthoquinones; D051780:Sterol Regulatory Element Binding Protein 1; C118460:beta-hydroxyisovalerylshikonin; C016101:shikonin; D013230:Stearoyl-CoA Desaturase; D000445:Aldehyde Oxidoreductases; C027902:fatty acid reductase; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase