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Article

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

  • Authors:
    • Jong-Hyeok Ha
    • Jaewoong Jang
    • Sang-In Chung
    • Yoosik Yoon
  • View Affiliations / Copyright

    Affiliations: Department of Microbiology, Chung-Ang University College of Medicine, Seoul 156-756, Republic of Korea
  • Pages: 816-824
    |
    Published online on: February 8, 2016
       https://doi.org/10.3892/ijmm.2016.2484
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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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1 

Grundy SM: Obesity, metabolic syndrome, and cardiovascular disease. J Clin Endocrinol Metab. 89:2595–2600. 2004. View Article : Google Scholar : PubMed/NCBI

2 

Farmer SR: Transcriptional control of adipocyte formation. Cell Metab. 4:263–273. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Rosen ED and MacDougald OA: Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol. 7:885–896. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Rosen ED, Walkey CJ, Puigserver P and Spiegelman BM: Transcriptional regulation of adipogenesis. Genes Dev. 14:1293–1307. 2000.PubMed/NCBI

5 

Hardie DG, Ross FA and Hawley SA: AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol. 13:251–262. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Makinde AO, Gamble J and Lopaschuk GD: Upregulation of 5′-AMP-activated protein kinase is responsible for the increase in myocardial fatty acid oxidation rates following birth in the newborn rabbit. Circ Res. 80:482–489. 1997. View Article : Google Scholar : PubMed/NCBI

7 

Ojuka EO, Jones TE, Nolte LA, Chen M, Wamhoff BR, Sturek M and Holloszy JO: Regulation of GLUT4 biogenesis in muscle: evidence for involvement of AMPK and Ca2+. Am J Physiol Endocrinol Metab. 282:E1008–E1013. 2002. View Article : Google Scholar : PubMed/NCBI

8 

Fazakerley DJ, Holman GD, Marley A, James DE, Stöckli J and Coster ACF: Kinetic evidence for unique regulation of GLUT4 trafficking by insulin and AMP-activated protein kinase activators in L6 myotubes. J Biol Chem. 285:1653–1660. 2010. View Article : Google Scholar :

9 

Mihaylova MM and Shaw RJ: The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nat Cell Biol. 13:1016–1023. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Steinberg GR and Kemp BE: AMPK in health and disease. Physiol Rev. 89:1025–1078. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Li Y, Xu S, Mihaylova MM, Zheng B, Hou X, Jiang B, Park O, Luo Z, Lefai E, Shyy JY, et al: AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell Metab. 13:376–388. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Kim JB, Wright HM, Wright M and Spiegelman BM: ADD1/SREBP1 activates PPARgamma through the production of endogenous ligand. Proc Natl Acad Sci USA. 95:4333–4337. 1998. View Article : Google Scholar : PubMed/NCBI

13 

Chen X, Yang L, Oppenheim JJ and Howard MZ: Cellular pharmacology studies of shikonin derivatives. Phytother Res. 16:199–209. 2002. View Article : Google Scholar : PubMed/NCBI

14 

Ito Y, Onobori K, Yamazaki T and Kawamura Y: Tigloylshikonin, a new minor Shikonin derivative, from the roots and the commercial root extract of Lithospermum erythrorhizon. Chem Pharm Bull (Tokyo). 59:117–119. 2011. View Article : Google Scholar

15 

Li J, Zhang D, Ward KM, Prendergast GC and Ayene IS: Hydroxyethyl disulfide as an efficient metabolic assay for cell viability in vitro. Toxicol In Vitro. 26:603–612. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Gustafson B and Smith U: Cytokines promote Wnt signaling and inflammation and impair the normal differentiation and lipid accumulation in 3T3-L1 preadipocytes. J Biol Chem. 281:9507–9516. 2006. View Article : Google Scholar : PubMed/NCBI

17 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

18 

Paton CM and Ntambi JM: Biochemical and physiological function of stearoyl-CoA desaturase. Am J Physiol Endocrinol Metab. 297:E28–E37. 2009. View Article : Google Scholar :

19 

Shimomura I, Bashmakov Y, Ikemoto S, Horton JD, Brown MS and Goldstein JL: Insulin selectively increases SREBP-1c mRNA in the livers of rats with streptozotocin-induced diabetes. Proc Natl Acad Sci USA. 96:13656–13661. 1999. View Article : Google Scholar : PubMed/NCBI

20 

Magaña MM, Lin SS, Dooley KA and Osborne TF: Sterol regulation of acetyl coenzyme A carboxylase promoter requires two interdependent binding sites for sterol regulatory element binding proteins. J Lipid Res. 38:1630–1638. 1997.PubMed/NCBI

21 

Fajas L, Schoonjans K, Gelman L, Kim JB, Najib J, Martin G, Fruchart JC, Briggs M, Spiegelman BM and Auwerx J: Regulation of peroxisome proliferator-activated receptor gamma expression by adipocyte differentiation and determination factor 1/sterol regulatory element binding protein 1: implications for adipocyte differentiation and metabolism. Mol Cell Biol. 19:5495–5503. 1999. View Article : Google Scholar : PubMed/NCBI

22 

Bijland S, Mancini SJ and Salt IP: Role of AMP-activated protein kinase in adipose tissue metabolism and inflammation. Clin Sci (Lond). 124:491–507. 2013. View Article : Google Scholar

23 

Lee H, Kang R, Bae S and Yoon Y: AICAR, an activator of AMPK, inhibits adipogenesis via the WNT/β-catenin pathway in 3T3-L1 adipocytes. Int J Mol Med. 28:65–71. 2011.PubMed/NCBI

24 

Zhang C, Shin DJ and Osborne TF: A simple promoter containing two Sp1 sites controls the expression of sterol-regulatory-element-binding protein 1a (SREBP-1a). Biochem J. 386:161–168. 2005. View Article : Google Scholar :

25 

Amemiya-Kudo M, Shimano H, Yoshikawa T, Yahagi N, Hasty AH, Okazaki H, Tamura Y, Shionoiri F, Iizuka Y, Ohashi K, et al: Promoter analysis of the mouse sterol regulatory element-binding protein-1c gene. J Biol Chem. 275:31078–31085. 2000. View Article : Google Scholar : PubMed/NCBI

26 

Rayalam S, Della-Fera MA and Baile CA: Phytochemicals and regulation of the adipocyte life cycle. J Nutr Biochem. 19:717–726. 2008. View Article : Google Scholar : PubMed/NCBI

27 

Shirwany NA and Zou MH: AMPK in cardiovascular health and disease. Acta Pharmacol Sin. 31:1075–1084. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Xiao X and Song BL: SREBP: a novel therapeutic target. Acta Biochim Biophys Sin (Shanghai). 45:2–10. 2013. View Article : Google Scholar

29 

Eberlé D, Hegarty B, Bossard P, Ferré P and Foufelle F: SREBP transcription factors: master regulators of lipid homeostasis. Biochimie. 86:839–848. 2004. View Article : Google Scholar : PubMed/NCBI

30 

Hwang JT, Kwon DY and Yoon SH: AMP-activated protein kinase: A potential target for the diseases prevention by natural occurring polyphenols. N Biotechnol. 26:17–22. 2009. View Article : Google Scholar : PubMed/NCBI

31 

Chen YC, Zeng XY, He Y, Liu H, Wang B, Zhou H, Chen JW, Liu PQ, Gu LQ, Ye JM and Huang ZS: Rutaecarpine analogues reduce lipid accumulation in adipocytes via inhibiting adipogenesis/lipogenesis with AMPK activation and UPR suppression. ACS Chem Biol. 8:2301–2311. 2013. View Article : Google Scholar : PubMed/NCBI

32 

He Y, Li Y, Zhao T, Wang Y and Sun C: Ursolic acid inhibits adipogenesis in 3T3-L1 adipocytes through LKB1/AMPK pathway. PLoS One. 8:e701352013. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Ha J, Jang J, Chung S and Yoon Y: AMPK and SREBP-1c mediate the anti-adipogenic effect of β-hydroxyisovalerylshikonin. Int J Mol Med 37: 816-824, 2016.
APA
Ha, J., Jang, J., Chung, S., & Yoon, Y. (2016). AMPK and SREBP-1c mediate the anti-adipogenic effect of β-hydroxyisovalerylshikonin. International Journal of Molecular Medicine, 37, 816-824. https://doi.org/10.3892/ijmm.2016.2484
MLA
Ha, J., Jang, J., Chung, S., Yoon, Y."AMPK and SREBP-1c mediate the anti-adipogenic effect of β-hydroxyisovalerylshikonin". International Journal of Molecular Medicine 37.3 (2016): 816-824.
Chicago
Ha, J., Jang, J., Chung, S., Yoon, Y."AMPK and SREBP-1c mediate the anti-adipogenic effect of β-hydroxyisovalerylshikonin". International Journal of Molecular Medicine 37, no. 3 (2016): 816-824. https://doi.org/10.3892/ijmm.2016.2484
Copy and paste a formatted citation
x
Spandidos Publications style
Ha J, Jang J, Chung S and Yoon Y: AMPK and SREBP-1c mediate the anti-adipogenic effect of β-hydroxyisovalerylshikonin. Int J Mol Med 37: 816-824, 2016.
APA
Ha, J., Jang, J., Chung, S., & Yoon, Y. (2016). AMPK and SREBP-1c mediate the anti-adipogenic effect of β-hydroxyisovalerylshikonin. International Journal of Molecular Medicine, 37, 816-824. https://doi.org/10.3892/ijmm.2016.2484
MLA
Ha, J., Jang, J., Chung, S., Yoon, Y."AMPK and SREBP-1c mediate the anti-adipogenic effect of β-hydroxyisovalerylshikonin". International Journal of Molecular Medicine 37.3 (2016): 816-824.
Chicago
Ha, J., Jang, J., Chung, S., Yoon, Y."AMPK and SREBP-1c mediate the anti-adipogenic effect of β-hydroxyisovalerylshikonin". International Journal of Molecular Medicine 37, no. 3 (2016): 816-824. https://doi.org/10.3892/ijmm.2016.2484
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