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Persimmon tannin represses 3T3-L1 preadipocyte differentiation via up-regulating expression of miR-27 and down-regulating expression of peroxisome proliferator-activated receptor-γ in the early phase of adipogenesis

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Abstract

Purpose

Currently, obesity has become a worldwide health problem. Adipocyte differentiation is closely associated with the onset of obesity. Our previous studies suggested that persimmon tannin might be a potent anti-adipogenic dietary bioactive compound. However, the mechanism of persimmon tannin on adipocyte differentiation is still unknown. The purpose of this study was to investigate the effect of persimmon tannin on adipogenic differentiation in 3T3-L1 preadipocytes and the underlying mechanisms.

Methods

Adipogenic differentiation was induced by cocktail in the presence or absence of persimmon tannin. Intracellular lipid accumulation was determined by Oil red O staining and enzymatic colorimetric methods. Gene expression and protein levels were measured by real time RT-PCR and Western blot.

Results

Persimmon tannin inhibited intracellular lipid accumulation markedly, and the inhibitory effect was largely limited to the early stage of adipocyte differentiation. Persimmon tannin suppressed the expression of C/EBPα and peroxisome proliferator-activated receptor-γ (PPARγ), significantly. Furthermore, genes related to lipogenesis, such as sterol regulatory element-binding protein 1, were down-regulated by persimmon tannin. In addition, adipocyte fatty acid binding protein (aP2), which is a target gene of PPARγ, was suppressed by persimmon tannin notably. Correspondingly, the expression of miR-27a and miR-27b were up-regulated by persimmon tannin from Day 2 to Day 8 significantly.

Conclusion

Persimmon tannin inhibited adipocyte differentiation through regulation of PPARγ, C/EBPα and miR-27 in early stage of adipogenesis.

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References

  1. Wang S, Moustaid-Moussa N, Chen L, Mo H, Shastri A, Su R, Bapat P, Kwun I, Shen CL (2014) Novel insights of dietary polyphenols and obesity. J Nutr Biochem 25:1–18

    Article  Google Scholar 

  2. Min SY, Yang H, Seo SG, Shin SH, Chung MY, Kim J, Lee SJ, Lee HJ, Lee KW (2013) Cocoa polyphenols suppress adipogenesis in vitro and obesity in vivo by targeting insulin receptor. Int J Obes (Lond) 37:584–592

    Article  CAS  Google Scholar 

  3. Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, Blomqvist L, Hoffstedt J, Naslund E, Britton T, Concha H, Hassan M, Ryden M, Frisen J, Arner P (2008) Dynamics of fat cell turnover in humans. Nature 453:783–787

    Article  CAS  Google Scholar 

  4. Gregoire FM, Smas CM, Sul HS (1998) Understanding adipocyte differentiation. Physiol Rev 78:783–809

    CAS  Google Scholar 

  5. Tang QQ, Lane MD (2012) Adipogenesis: from stem cell to adipocyte. Annu Rev Biochem 81:715–736

    Article  CAS  Google Scholar 

  6. Rosen ED, Walkey CJ, Puigserver P, Spiegelman BM (2000) Transcriptional regulation of adipogenesis. Genes Dev 14:1293–1307

    CAS  Google Scholar 

  7. Rosen ED, MacDougald OA (2006) Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol 7:885–896

    Article  CAS  Google Scholar 

  8. Jeong YS, Hong JH, Cho KH, Jung HK (2012) Grape skin extract reduces adipogenesis- and lipogenesis-related gene expression in 3T3-L1 adipocytes through the peroxisome proliferator-activated receptor-gamma signaling pathway. Nutr Res 32:514–521

    Article  CAS  Google Scholar 

  9. Quan HY, Baek NI, Chung SH (2012) Licochalcone A prevents adipocyte differentiation and lipogenesis via suppression of peroxisome proliferator-activated receptor gamma and sterol regulatory element-binding protein pathways. J Agric Food Chem 60:5112–5120

    Article  CAS  Google Scholar 

  10. Sanderson M, Mazibuko SE, Joubert E, de Beer D, Johnson R, Pheiffer C, Louw J, Muller CJ (2014) Effects of fermented rooibos (Aspalathus linearis) on adipocyte differentiation. Phytomedicine 21:109–117

    Article  CAS  Google Scholar 

  11. Rossmeisl M, Flachs P, Brauner P, Sponarova J, Matejkova O, Prazak T, Ruzickova J, Bardova K, Kuda O, Kopecky J (2004) Role of energy charge and AMP-activated protein kinase in adipocytes in the control of body fat stores. Int J Obes Relat Metab Disord 28(Suppl 4):S38–S44

    Article  CAS  Google Scholar 

  12. Ono M, Fujimori K (2011) Antiadipogenic effect of dietary apigenin through activation of AMPK in 3T3-L1 cells. J Agric Food Chem 59:13346–13352

    Article  CAS  Google Scholar 

  13. Ku HC, Liu HS, Hung PF, Chen CL, Liu HC, Chang HH, Tsuei YW, Shih LJ, Lin CL, Lin CM, Kao YH (2012) Green tea (−)-epigallocatechin gallate inhibits IGF-I and IGF-II stimulation of 3T3-L1 preadipocyte mitogenesis via the 67-kDa laminin receptor, but not AMP-activated protein kinase pathway. Mol Nutr Food Res 56:580–592

    Article  CAS  Google Scholar 

  14. Chen L, Song J, Cui J, Hou J, Zheng X, Li C, Liu L (2013) microRNAs regulate adipocyte differentiation. Cell Biol Int 37:533–546

    Article  CAS  Google Scholar 

  15. Karbiener M, Fischer C, Nowitsch S, Opriessnig P, Papak C, Ailhaud G, Dani C, Amri EZ, Scheideler M (2009) microRNA miR-27b impairs human adipocyte differentiation and targets PPARgamma. Biochem Biophys Res Commun 390:247–251

    Article  CAS  Google Scholar 

  16. Kim SY, Kim AY, Lee HW, Son YH, Lee GY, Lee J-W, Lee YS, Kim JB (2010) miR-27a is a negative regulator of adipocyte differentiation via suppressing PPARgamma expression. Biochem Biophys Res Commun 392:323–328

    Article  CAS  Google Scholar 

  17. Baselga-Escudero L, Blade C, Ribas-Latre A, Casanova E, Suarez M, Lluis Torres J, Josepa Salvado M, Arola L, Arola-Arnal A (2014) Resveratrol and EGCG bind directly and distinctively to miR-33a and miR-122 and modulate divergently their levels in hepatic cells. Nucleic Acids Res 42:882–892

    Article  CAS  Google Scholar 

  18. Arola-Arnal A, Blade C (2011) Proanthocyanidins modulate microRNA expression in human HepG2 cells. PLoS One 6:e25982

    Article  CAS  Google Scholar 

  19. Matsumoto K, S-i Yokoyama (2012) Induction of uncoupling protein-1 and -3 in brown adipose tissue by kaki-tannin in type 2 diabetic NSY/Hos mice. Food Chem Toxicol 50:184–190

    Article  CAS  Google Scholar 

  20. Zou B, Li CM, Chen JY, Dong XQ, Zhang Y, Du J (2012) High molecular weight persimmon tannin is a potent hypolipidemic in high-cholesterol diet fed rats. Food Res Int 48:970–977

    Article  CAS  Google Scholar 

  21. Gato N, Kadowaki A, Hashimoto N, Yokoyama S, Matsumoto K (2013) Persimmon fruit tannin-rich fiber reduces cholesterol levels in humans. Ann Nutr Metab 62:1–6

    Article  CAS  Google Scholar 

  22. Zou B, Ge ZZ, Zhang Y, Du J, Xu Z, Li CM (2014) Persimmon Tannin accounts for hypolipidemic effects of persimmon through activating of AMPK and suppressing NF-kappaB activation and inflammatory responses in high-fat diet rats. Food Funct 5:1536–1546

    Article  CAS  Google Scholar 

  23. Gu HF, Li CM, Xu YJ, Hu WF, Chen MH, Wan QH (2008) Structural features and antioxidant activity of tannin from persimmon pulp. Food Res Int 41:208–217

    Article  CAS  Google Scholar 

  24. Li C, Leverence R, Trombley JD, Xu S, Yang J, Tian Y, Reed JD, Hagerman AE (2010) High molecular weight persimmon (Diospyros kaki L.) proanthocyanidin: a highly galloylated, a-linked tannin with an unusual flavonol terminal unit, myricetin. J Agric Food Chem 58:9033–9042

    Article  CAS  Google Scholar 

  25. Gahler S, Otto K, Böhm V (2003) Alterations of vitamin C, total phenolics, and antioxidant capacity as affected by processing tomatoes to different products. J Agric Food Chem 51:7962–7968

    Article  CAS  Google Scholar 

  26. Zhang T, Sawada K, Yamamoto N, Ashida H (2013) 4-Hydroxyderricin and xanthoangelol from Ashitaba (Angelica keiskei) suppress differentiation of preadiopocytes to adipocytes via AMPK and MAPK pathways. Mol Nutr Food Res 57:1729–1740

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  28. Jeong Y, Jung H, Cho K-H, Youn K-S, Hong J-H (2011) Anti-obesity effect of grape skin extract in 3T3-L1 adipocytes. Food Sci Biotechnol 20:635–642

    Article  Google Scholar 

  29. Kim CY, Le TT, Chen C, Cheng J-X, Kim K-H (2011) Curcumin inhibits adipocyte differentiation through modulation of mitotic clonal expansion. J Nutr Biochem 22:910–920

    Article  CAS  Google Scholar 

  30. Choi Y, Kim Y, Ham H, Park Y, Jeong HS, Lee J (2011) Nobiletin suppresses adipogenesis by regulating the expression of adipogenic transcription factors and the activation of AMP-activated protein kinase (AMPK). J Agric Food Chem 59:12843–12849

    Article  CAS  Google Scholar 

  31. Chen YY, Lee MH, Hsu CC, Wei CL, Tsai YC (2012) Methyl cinnamate inhibits adipocyte differentiation via activation of the CaMKK2–AMPK pathway in 3T3-L1 preadipocytes. J Agric Food Chem 60:955–963

    Article  CAS  Google Scholar 

  32. Kwon JY, Seo SG, Yue S, Cheng JX, Lee KW, Kim KH (2012) An inhibitory effect of resveratrol in the mitotic clonal expansion and insulin signaling pathway in the early phase of adipogenesis. Nutr Res 32:607–616

    Article  CAS  Google Scholar 

  33. Hung PF, Wu BT, Chen HC, Chen YH, Chen CL, Wu MH, Liu HC, Lee MJ, Kao YH (2005) Antimitogenic effect of green tea (−)-epigallocatechin gallate on 3T3-L1 preadipocytes depends on the ERK and Cdk2 pathways. Am J Physiol Cell Physiol 288:C1094–C1108

    Article  CAS  Google Scholar 

  34. Ren D, Collingwood TN, Rebar EJ, Wolffe AP, Camp HS (2002) PPARgamma knockdown by engineered transcription factors: exogenous PPARgamma2 but not PPARgamma1 reactivates adipogenesis. Genes Dev 16:27–32

    Article  CAS  Google Scholar 

  35. Kim H, Hiraishi A, Tsuchiya K, Sakamoto K (2010) (−) Epigallocatechin gallate suppresses the differentiation of 3T3-L1 preadipocytes through transcription factors FoxO1 and SREBP1c. Cytotechnology 62:245–255

    Article  CAS  Google Scholar 

  36. Hwang JT, Park IJ, Shin JI, Lee YK, Lee SK, Baik HW, Ha J, Park OJ (2005) Genistein, EGCG, and capsaicin inhibit adipocyte differentiation process via activating AMP-activated protein kinase. Biochem Biophys Res Commun 338:694–699

    Article  CAS  Google Scholar 

  37. Tian Y, Zou B, Li C-m, Yang J, Xu S-f, Hagerman AE (2012) High molecular weight persimmon tannin is a potent antioxidant both ex vivo and in vivo. Food Res Int 45:26–30

    Article  CAS  Google Scholar 

  38. Lin Q, Gao ZG, Alarcon RM, Ye JP, Yun Z (2009) A role of miR-27 in the regulation of adipogenesis. FEBS J 276:2348–2358

    Article  CAS  Google Scholar 

  39. Verstraeten SV, Jaggers GK, Fraga CG, Oteiza PI (2013) Procyanidins can interact with Caco-2 cell membrane lipid rafts: involvement of cholesterol. BBA-Biomembranes 1828:2646–2653

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the Chinese Ministry Program for New Century Excellent Talents in University (NCET-12-0865), the National Natural Science Foundation of China (No. 31271833), Special Fund for Agro-scientific Research in the Public Interest (No. 201203047) and Fundamental Research Funds for the Central Universities (2013PY022).

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The authors declare no conflict of interest.

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Correspondence to Chunmei Li.

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Zou, B., Ge, Z., Zhu, W. et al. Persimmon tannin represses 3T3-L1 preadipocyte differentiation via up-regulating expression of miR-27 and down-regulating expression of peroxisome proliferator-activated receptor-γ in the early phase of adipogenesis. Eur J Nutr 54, 1333–1343 (2015). https://doi.org/10.1007/s00394-014-0814-9

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  • DOI: https://doi.org/10.1007/s00394-014-0814-9

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