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Resveratrol Upregulated SIRT1, FOXO1, and Adiponectin and Downregulated PPARγ1–3 mRNA Expression in Human Visceral Adipocytes

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Abstract

Background

The SIRT1 enzyme is involved in adipose tissue (AT) lipolysis. FOXO1 is a protein that plays a significant role in regulating metabolism. Adiponectin is an adipokine, secreted by the AT, which has been considered to have an antiobesity function. PPARγ is one of the key actors in adipocytes differentiation. This study was undertaken to investigate whether resveratrol can regulate SIRT1, FOXO1, adiponectin, PPARγ1–3, and PPARβ/δ in human AT.

Methods

The effects of resveratrol were analyzed in freshly isolated adipocytes prepared from visceral fat tissue samples obtained during bariatric surgery. Genes messenger ribonucleic acid (mRNA) levels were determined by qRT-PCR.

Results

Ours results show that resveratrol modulates the studied genes, increasing SIRT1 (p = 0.021), FOXO1 (p = 0.001), and adiponectin (p = 0.025) mRNA expression and decreasing PPARγ1–3 (p = 0.003) mRNA in human visceral adipocytes.

Conclusions

Resveratrol, in vitro and at low concentration, modulates genes that are related to lipid metabolism, possibly preventing metabolic disease in human visceral adipose tissue (VAT).

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Abbreviations

AT:

Adipose tissue

VAT:

Visceral adipose tissue

FOXO1:

Forkhead/winged helix

SIRT1:

Sirtuin 1

PPAR:

Peroxisome proliferator-activated receptors

qRT-PCR:

Quantitative real-time polymerase chain reaction

References

  1. Marchesini G, Moscatiello S, Domizio SD et al. Obesity-associated liver disease. J Clin Endocrinol Metab. 2008;93(11 Suppl 1):S74–80.

    Article  CAS  PubMed  Google Scholar 

  2. Bai L, Pang WJ, Yang, YJ et al. Modulation of Sirt1 by resveratrol and nicotinamide alters proliferation and differentiation of pig preadipocytes. Mol Cell Biochem. 2008;307(1–2):129–40.

    CAS  PubMed  Google Scholar 

  3. Harikumar KB, Aggarwal BB. Resveratrol: a multitargeted agent for age-associated chronic diseases. Cell Cycle. 2008;7(8):1020–35.

    Article  CAS  PubMed  Google Scholar 

  4. Rivera L, Moron R, Zarzuelo A et al. Long-term resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats. Biochem Pharmacol. 2009;77(6):1053–63.

    Article  CAS  PubMed  Google Scholar 

  5. Floyd ZE, Wang ZQ, Kilroy G et al. Modulation of peroxisome proliferator-activated receptor gamma stability and transcriptional activity in adipocytes by resveratrol. Metabolism. 2008;57(7 Suppl 1):S32–8.

    Article  CAS  PubMed  Google Scholar 

  6. Baur JA, Pearson KJ, Price NL et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006;444(7117):337–42.

    Article  CAS  PubMed  Google Scholar 

  7. Lagouge M, Argmann C, Gerhart-Hines Z et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006;127(6):1109–22.

    Article  CAS  PubMed  Google Scholar 

  8. Picard F, Kurtev M, Chung N et al. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature. 2004;429(6993):771–6.

    Article  CAS  PubMed  Google Scholar 

  9. Howitz KT, Bitterman KJ, Cohen HY et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003;425(6954):191–6.

    Article  CAS  PubMed  Google Scholar 

  10. Wang F, Tong Q. SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1’s repressive interaction with PPARgamma. Mol Biol Cell. 2009;20(3):801–8.

    Article  CAS  PubMed  Google Scholar 

  11. Subauste AR, Burant CF. Role of FoxO1 in FFA-induced oxidative stress in adipocytes. Am J Physiol Endocrinol Metab. 2007;293(1):E159–64.

    Article  CAS  PubMed  Google Scholar 

  12. Ma H, Gomez V, Lu L et al. Expression of adiponectin and its receptors in livers of morbidly obese patients with non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2009;24(2):233–7.

    Article  CAS  PubMed  Google Scholar 

  13. Rogers CQ, Ajmo JM, You M. Adiponectin and alcoholic fatty liver disease. IUBMB Life. 2008;60(12):790–7.

    Article  CAS  PubMed  Google Scholar 

  14. Kota BP, Huang TH, Roufogalis BD. An overview on biological mechanisms of PPARs. Pharmacol Res. 2005;51(2):85–94.

    Article  CAS  PubMed  Google Scholar 

  15. Semple RK, Chatterjee VK, O’Rahilly S. PPAR gamma and human metabolic disease. J Clin Invest. 2006;116(3):581–9.

    Article  CAS  PubMed  Google Scholar 

  16. Mitsuishi M, Miyashita K, Itoh H. Metabolic syndrome. Nippon Rinsho. 2009;67(2):321–6.

    PubMed  Google Scholar 

  17. Rodbell M. Metabolism of isolated fat cells: I. Effects of hormones on glucose metabolism and lipolysis. J Biol Chem. 1964;239:375–80.

    CAS  PubMed  Google Scholar 

  18. Rieusset J, Andreelli F, Auboeuf D et al. Insulin acutely regulates the expression of the peroxisome proliferator-activated receptor-gamma in human adipocytes. Diabetes. 1999;48(4):699–705.

    Article  CAS  PubMed  Google Scholar 

  19. Walle T, Hsieh F, DeLegge MH et al. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos. 2004;32(12):1377–82.

    Article  CAS  PubMed  Google Scholar 

  20. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25(4):402–8.

    Article  CAS  PubMed  Google Scholar 

  21. Shan T, Wang Y, Wu T et al. Porcine sirtuin 1 gene clone, expression pattern, and regulation by resveratrol. J Anim Sci. 2009;87(3):895–904.

    Article  CAS  PubMed  Google Scholar 

  22. Alcain FJ, Villalba JM. Sirtuin activators. Expert Opin Ther Pat. 2009;19(4):403–14.

    Article  CAS  PubMed  Google Scholar 

  23. Costa CS, Hammes TO, Rohden F et al. SIRT1 transcription is decreased in visceral adipose tissue of morbidly obese patients with severe hepatic steatosis. Obes Surg. 2009.

  24. Nisoli E, Clementi E, Carruba MO et al. Defective mitochondrial biogenesis: a hallmark of the high cardiovascular risk in the metabolic syndrome? Circ Res. 2007;100(6):795–806.

    Article  CAS  PubMed  Google Scholar 

  25. Gross DN, van den Heuvel AP, Birnbaum MJ. The role of FoxO in the regulation of metabolism. Oncogene. 2008;27(16):2320–36.

    Article  CAS  PubMed  Google Scholar 

  26. Pillarisetti S. A review of Sirt1 and Sirt1 modulators in cardiovascular and metabolic diseases. Recent Pat Cardiovasc Drug Discov. 2008;3(3):156–64.

    Article  CAS  PubMed  Google Scholar 

  27. Qiao L, Shao J. SIRT1 regulates adiponectin gene expression through Foxo1-C/enhancer-binding protein alpha transcriptional complex. J Biol Chem. 2006;281(52):39915–24.

    Article  CAS  PubMed  Google Scholar 

  28. Wang YX, Lee CH, Tiep S et al. Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity. Cell. 2003;113(2):159–70.

    Article  CAS  PubMed  Google Scholar 

  29. Bortolotto JW, Margis R, Ferreira ACB et al. Adipose tissue distribution and quantification of PPARbeta/delta and PPARgamma1–3 mRNAs: discordant gene expression in subcutaneous, retroperitoneal and visceral adipose tissue of morbidly obese patients. Obes Surg. 2007;17(7):934–40.

    Article  PubMed  Google Scholar 

  30. Rayalam S, Yang JY, Ambati S et al. Resveratrol induces apoptosis and inhibits adipogenesis in 3T3-L1 adipocytes. Phytother Res. 2008;22(10):1367–71.

    Article  CAS  PubMed  Google Scholar 

  31. Pang WJ, Sun SD, Bai L et al. Effects of resveratrol on pig primary preadipocytes proliferation, differentiation and transcription expression of Sirt1 gene. Sheng Wu Gong Cheng Xue Bao. 2006;22(5):850–5.

    CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by research grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and the Fundação de Apoio à Pesquisa do Rio Grande do Sul (FAPERGS). Dr. R. Margis is a recipient of a research fellowship from the CNPq.

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Correspondence to Regina Maria Guaragna.

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Costa, C.d.S., Rohden, F., Hammes, T.O. et al. Resveratrol Upregulated SIRT1, FOXO1, and Adiponectin and Downregulated PPARγ1–3 mRNA Expression in Human Visceral Adipocytes. OBES SURG 21, 356–361 (2011). https://doi.org/10.1007/s11695-010-0251-7

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  • DOI: https://doi.org/10.1007/s11695-010-0251-7

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