Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
June-2017 Volume 15 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
June-2017 Volume 15 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Berberine activates AMPK to suppress proteolytic processing, nuclear translocation and target DNA binding of SREBP-1c in 3T3-L1 adipocytes

  • Authors:
    • Jaewoong Jang
    • Yoonju Jung
    • Seong Jun Seo
    • Seok‑Min Kim
    • Yae Jie Shim
    • Soo Hyun Cho
    • Sang‑In Chung
    • Yoosik Yoon
  • View Affiliations / Copyright

    Affiliations: Department of Microbiology, Chung‑Ang University College of Medicine, Dongjak‑gu, Seoul 156‑756, Republic of Korea, Department of Dermatology, Chung‑Ang University College of Medicine, Dongjak‑gu, Seoul 156‑756, Republic of Korea, School of Mechanical Engineering, Chung‑Ang University, Dongjak‑gu, Seoul 156‑756, Republic of Korea, College of General Studies, Sangmyung University, Jongno‑gu, Seoul 110‑743, Republic of Korea, Department of Family Medicine, College of Medicine, Chung‑Ang University Hospital, Dongjak‑gu, Seoul 156‑755, Republic of Korea
    Copyright: © Jang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4139-4147
    |
    Published online on: April 26, 2017
       https://doi.org/10.3892/mmr.2017.6513
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

AMP-activated protein kinase (AMPK) and sterol regulatory element binding protein (SREBP)‑1c are major therapeutic targets in the treatment of metabolic diseases. In the present study, the fat‑reducing mechanisms of berberine (BBR), a natural isoquinoline, was investigated by examining the AMPK‑mediated modulation of SREBP‑1c in 3T3‑L1 adipocytes. BBR activated AMPK in a dose‑ and time‑dependent manner, and increased the phosphorylation of the 125‑kDa precursor form of SREBP‑1c, which suppressed its proteolytic processing into the mature 68‑kDa form and its subsequent nuclear translocation. The binding of nuclear SREBP‑1c to its E‑box motif‑containing target DNA sequence was decreased following treatment with BBR, which led to a decrease in the expression of lipogenic genes and subsequently reduced intracellular fat accumulation. Transfection with AMPKα1 siRNA, and not control siRNA, inhibited BBR‑induced phosphorylation of the 125‑kDa SREBP‑1c, which confirmed that AMPK was responsible for phosphorylating SREBP‑1c. AMPKα1 siRNA transfection rescued the proteolytic processing, nuclear translocation and target DNA binding of SREBP‑1c that had been suppressed by BBR. In addition, BBR‑induced suppression of lipogenic gene expression and intracellular fat accumulation were rescued by AMPKα1 siRNA transfection. In conclusion, the results of the present study demonstrate that BBR activates AMPK to induce phosphorylation of SREBP‑1c, thereby suppressing proteolytic processing, nuclear translocation and target DNA binding of SREBP‑1c, which leads to a reduction in lipogenic gene expression and intracellular fat accumulation. The results of the present study indicate that BBR may be a potential candidate for the development of drugs to treat obesity.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

View References

1 

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

2 

Daval M, Diot-Dupuy F, Bazin R, Hainault I, Viollet B, Vaulont S, Hajduch E, Ferré P and Foufelle F: Anti-lipolytic action of AMP-activated protein kinase in rodent adipocytes. J Biol Chem. 280:25250–25257. 2005. View Article : Google Scholar

3 

Gowans GJ, Hawley SA, Ross FA and Hardie DG: AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation. Cell Metab. 18:556–566. 2013. View Article : Google Scholar :

4 

Vuddanda PR, Chakraborty S and Singh S: Berberine: A potential phytochemical with multispectrum therapeutic activities. Expert Opin Investig Drugs. 19:1297–1307. 2010. View Article : Google Scholar

5 

Lee YS, Kim WS, Kim KH, Yoon MJ, Cho HJ, Shen Y, Ye JM, Lee CH, Oh WK, Kim CT, et al: Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes. 55:2256–2264. 2006. View Article : Google Scholar

6 

Turner N, Li JY, Gosby A, To SW, Cheng Z, Miyoshi H, Taketo MM, Cooney GJ, Kraegen EW, James DE, et al: Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: A mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. Diabetes. 57:1414–1418. 2008. View Article : Google Scholar

7 

Jeon TI and Osborne TF: SREBPs: Metabolic integrators in physiology and metabolism. Trends Endocrinol Metab. 23:65–72. 2012. View Article : Google Scholar

8 

Li GS, Liu XH, Zhu H, Huang L, Liu YL, Ma CM and Qin C: Berberine-improved visceral white adipose tissue insulin resistance associated with altered sterol regulatory element-binding proteins, liver × receptors and peroxisome proliferator-activated receptors transcriptional programs in diabetic hamsters. Biol Pharm Bull. 34:644–654. 2011. View Article : Google Scholar

9 

Hu Y, Kutscher E and Davies GE: Berberine inhibits SREBP-1-related clozapine and risperidone induced adipogenesis in 3T3-L1 cells. Phytother Res. 24:1831–1838. 2010. View Article : Google Scholar

10 

Huang C, Zhang Y, Gong Z, Sheng X, Li Z, Zhang W and Qin Y: Berberine inhibits 3T3-L1 adipocyte differentiation through the PPARgamma pathway. Biochem Biophys Res Commun. 348:571–578. 2006. View Article : Google Scholar

11 

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

12 

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

13 

Lee H, Bae S and Yoon Y: The anti-adipogenic effects of (−)epigallocatechin gallate are dependent on the WNT/β-catenin pathway. J Nutr Biochem. 24:1232–1240. 2013. View Article : Google Scholar

14 

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

15 

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 :

16 

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

17 

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 :

18 

Schoonjans K, Gelman L, Haby C, Briggs M and Auwerx J: Induction of LPL gene expression by sterols is mediated by a sterol regulatory element and is independent of the presence of multiple E boxes. J Mol Biol. 304:323–334. 2000. View Article : Google Scholar

19 

Barber MC, Vallance AJ, Kennedy HT and Travers MT: Induction of transcripts derived from promoter III of the acetyl-CoA carboxylase-alpha gene in mammary gland is associated with recruitment of SREBP-1 to a region of the proximal promoter defined by a DNase I hypersensitive site. Biochem J. 375:489–501. 2003. View Article : Google Scholar :

20 

Griffin MJ and Sul HS: Insulin regulation of fatty acid synthase gene transcription: Roles of USF and SREBP-1c. IUBMB Life. 56:595–600. 2004. View Article : Google Scholar

21 

Bene H, Lasky D and Ntambi JM: Cloning and characterization of the human stearoyl-CoA desaturase gene promoter: Transcriptional activation by sterol regulatory element binding protein and repression by polyunsaturated fatty acids and cholesterol. Biochem Biophys Res Commun. 284:1194–1198. 2001. View Article : Google Scholar

22 

Wang X, Sato R, Brown MS, Hua X and Goldstein JL: SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis. Cell. 77:53–62. 1994. View Article : Google Scholar

23 

Eberle 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

24 

Zhao QH, Wang SG, Liu SX, Li JP, Zhang YX, Sun ZY, Fan QM and Tian JW: PPARγ forms a bridge between DNA methylation and histone acetylation at the C/EBPα gene promoter to regulate the balance between osteogenesis and adipogenesis of bone marrow stromal cells. FEBS J. 280:5801–5814. 2013. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Jang J, Jung Y, Seo SJ, Kim SM, Shim YJ, Cho SH, Chung SI and Yoon Y: Berberine activates AMPK to suppress proteolytic processing, nuclear translocation and target DNA binding of SREBP-1c in 3T3-L1 adipocytes. Mol Med Rep 15: 4139-4147, 2017.
APA
Jang, J., Jung, Y., Seo, S.J., Kim, S., Shim, Y.J., Cho, S.H. ... Yoon, Y. (2017). Berberine activates AMPK to suppress proteolytic processing, nuclear translocation and target DNA binding of SREBP-1c in 3T3-L1 adipocytes. Molecular Medicine Reports, 15, 4139-4147. https://doi.org/10.3892/mmr.2017.6513
MLA
Jang, J., Jung, Y., Seo, S. J., Kim, S., Shim, Y. J., Cho, S. H., Chung, S., Yoon, Y."Berberine activates AMPK to suppress proteolytic processing, nuclear translocation and target DNA binding of SREBP-1c in 3T3-L1 adipocytes". Molecular Medicine Reports 15.6 (2017): 4139-4147.
Chicago
Jang, J., Jung, Y., Seo, S. J., Kim, S., Shim, Y. J., Cho, S. H., Chung, S., Yoon, Y."Berberine activates AMPK to suppress proteolytic processing, nuclear translocation and target DNA binding of SREBP-1c in 3T3-L1 adipocytes". Molecular Medicine Reports 15, no. 6 (2017): 4139-4147. https://doi.org/10.3892/mmr.2017.6513
Copy and paste a formatted citation
x
Spandidos Publications style
Jang J, Jung Y, Seo SJ, Kim SM, Shim YJ, Cho SH, Chung SI and Yoon Y: Berberine activates AMPK to suppress proteolytic processing, nuclear translocation and target DNA binding of SREBP-1c in 3T3-L1 adipocytes. Mol Med Rep 15: 4139-4147, 2017.
APA
Jang, J., Jung, Y., Seo, S.J., Kim, S., Shim, Y.J., Cho, S.H. ... Yoon, Y. (2017). Berberine activates AMPK to suppress proteolytic processing, nuclear translocation and target DNA binding of SREBP-1c in 3T3-L1 adipocytes. Molecular Medicine Reports, 15, 4139-4147. https://doi.org/10.3892/mmr.2017.6513
MLA
Jang, J., Jung, Y., Seo, S. J., Kim, S., Shim, Y. J., Cho, S. H., Chung, S., Yoon, Y."Berberine activates AMPK to suppress proteolytic processing, nuclear translocation and target DNA binding of SREBP-1c in 3T3-L1 adipocytes". Molecular Medicine Reports 15.6 (2017): 4139-4147.
Chicago
Jang, J., Jung, Y., Seo, S. J., Kim, S., Shim, Y. J., Cho, S. H., Chung, S., Yoon, Y."Berberine activates AMPK to suppress proteolytic processing, nuclear translocation and target DNA binding of SREBP-1c in 3T3-L1 adipocytes". Molecular Medicine Reports 15, no. 6 (2017): 4139-4147. https://doi.org/10.3892/mmr.2017.6513
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team