Skip to main content
SpringerLink
Log in

Influence of resveratrol on endoplasmic reticulum stress and expression of adipokines in adipose tissues/adipocytes induced by high-calorie diet or palmitic acid

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

This study aimed to determine whether resveratrol treatment alleviates endoplasmic reticulum stress and changes the expression of adipokines in adipose tissues and cells.

Methods

8-week-old male C57BL/6 mice were fed a high-calorie diet (HCD group) or high-calorie diet supplemented with resveratrol (high-calorie diet  + resveratrol group) for 3 months. Insulin resistance, serum lipids and proinflammatory indices, the size and inflammatory cell infiltration in subcutaneous and visceral adipose tissues were analyzed. The gene expressions of endoplasmic reticulum stress, adipokines, and inflammatory cytokines were determined. The induced mature 3T3-L1 cells were pretreated with resveratrol and then palmitic acid, and the gene expressions of endoplasmic reticulum stress, adipokines, and inflammatory cytokines were determined.

Results

Subcutaneous and visceral adipose tissues in the high-calorie diet-fed mice exhibited adipocyte hypertrophy, inflammatory activation, and endoplasmic reticulum stress. Resveratrol alleviated high-calorie diet-induced insulin resistance and endoplasmic reticulum stress, increased expression of SIRT1, and reversed expression of adipokines in varying degrees in both subcutaneous and visceral adipose tissues. The effects of resveratrol on palmitic acid-treated adipocytes were similar to those shown in the tissues.

Conclusions

Resveratrol treatment obviously reversed adipocyte hypertrophy and insulin resistance by attenuating endoplasmic reticulum stress and inflammation, thus increasing the expression of SIRT1 and inverting the expression of adipokines in vivo and in vitro.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. R.H. Eckel, S.M. Grundy, P.Z. Zimmet, The metabolic syndrome. Lancet. 365, 1415–1428 (2005)

    Article  CAS  PubMed  Google Scholar 

  2. T. Wang, A. Jiang, Y. Guo, Y. Tan, G. Tang, M. Mai, H. Liu, J. Xiao, M. Li, X. Li, Deep sequencing of the transcriptome reveals inflammatory features of porcine visceral adipose tissue. Int. J. Biol. Sci. 9, 550–556 (2013)

    Article  PubMed  PubMed Central  Google Scholar 

  3. B. Antuna-Puente, B. Feve, S. Fellahi, J.P. Bastard, Adipokines: the missing link between insulin resistance and obesity. Diabetes. Metab. 34, 2–11 (2008)

    Article  CAS  PubMed  Google Scholar 

  4. S.P. Weisberg, D. McCann, M. Desai, M. Rosenbaum, R.L. Leibel, A.W. Ferrante Jr., Obesity is associated with macrophage accumulation in adipose tissue. J. Clin. Invest. 112, 1796–1808 (2003)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. K. Cusi, The role of adipose tissue and lipotoxicity in the pathogenesis of type 2 diabetes. Curr. Diab. Rep. 10, 306–315 (2010)

    Article  CAS  PubMed  Google Scholar 

  6. R.A. Luvizotto, A.F. Nascimento, E. Imaizumi, D.T. Pierine, S.J. Conde, C.R. Correa, K.J. Yeum, A.L. Ferreira, Lycopene supplementation modulates plasma concentrations and epididymal adipose tissue mRNA of leptin, resistin and IL-6 in diet-induced obese rats. Br. J. Nutr. 110, 1803–1809 (2013)

    Article  CAS  Google Scholar 

  7. M.F. Gregor, G.S. Hotamisligil, Thematic review series: adipocyte biology. Adipocyte stress: the endoplasmic reticulum and metabolic disease. J. Lipid. Res. 48, 1905–1914 (2007)

    Article  CAS  PubMed  Google Scholar 

  8. N. Kawasaki, R. Asada, A. Saito, S. Kanemoto, K. Imaizumi, Obesity-induced endoplasmic reticulum stress causes chronic inflammation in adipose tissue. Sci. Rep. 2, 799 (2012)

    Article  PubMed  PubMed Central  Google Scholar 

  9. W. Yu, Y.C. Fu, W. Wang, Cellular and molecular effects of resveratrol in health and disease. J. Cell. Biochem. 113, 752–759 (2012)

    Article  CAS  PubMed  Google Scholar 

  10. J.D. Malhotra, H. Miao, K. Zhang, A. Wolfson, S. Pennathur, S.W. Pipe, R.J. Kaufman, Antioxidants reduce endoplasmic reticulum stress and improve protein secretion. Proc. Natl. Acad. Sci. U. S. A. 105, 18525–18530 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. T.W. Jung, K.T. Lee, M.W. Lee, K.H. Ka, SIRT1 attenuates palmitate-induced endoplasmic reticulum stress and insulin resistance in HepG2 cells via induction of oxygen-regulated protein 150. Biochem. Biophys. Res. Commun. 422, 229–232 (2012)

    Article  CAS  PubMed  Google Scholar 

  12. S.E. Chow, C.H. Kao, Y.T. Liu, M.L. Cheng, Y.W. Yang, Y.K. Huang, C.C. Hsu, J.S. Wang, Resveratrol induced ER expansion and ER caspase-mediated apoptosis in human nasopharyngeal carcinoma cells. Apoptosis. 19, 527–541 (2014)

    Article  CAS  PubMed  Google Scholar 

  13. L.Q. Liu, Z.Q. Fan, Y.F. Tang, Z.J. Ke, The resveratrol attenuates ethanol-induced hepatocyte apoptosis via inhibiting ER-related caspase-12 activation and PDE activity in vitro. Alcohol. Clin. Exp. Res. 38, 683–693 (2014)

    Article  CAS  PubMed  Google Scholar 

  14. C. Li, L. Wang, K. Huang, L. Zheng, Endoplasmic reticulum stress in retinal vascular degeneration: protective role of resveratrol. Invest. Ophthalmol. Vis. Sci. 53, 3241–3249 (2012)

    Article  CAS  PubMed  Google Scholar 

  15. S. Li, C. Bouzar, C. Cottet-Rousselle, I. Zagotta, F. Lamarche, M. Wabitsch, M. Tokarska-Schlattner, P. Fischer-Posovszky, Resveratrol inhibits lipogenesis of 3T3-L1 and SGBS cells by inhibition of insulin signaling and mitochondrial mass increase. Biochim. Biophys. Acta. 1857, 643–652 (2016)

    Article  CAS  PubMed  Google Scholar 

  16. M. Lagouge, C. Argmann, Z. Gerhart-Hines, H. Meziane, C. Lerin, F. Daussin, N. Messadeq, J. Milne, P. Lambert, P. Elliott, B. Geny, M. Laakso, P. Puigserver, J. Auwerx, Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 127, 1109–1122 (2006)

    Article  CAS  PubMed  Google Scholar 

  17. Y. Lu, L. Qian, Q. Zhang, B. Chen, L. Gui, D. Huang, G. Chen, L. Chen, Palmitate induces apoptosis in mouse aortic endothelial cells and endothelial dysfunction in mice fed high-calorie and high-cholesterol diets. Life. Sci. 92, 1165–1173 (2013)

    Article  CAS  PubMed  Google Scholar 

  18. L.D. Han, J.F. Xia, Q.L. Liang, Y. Wang, Y.M. Wang, P. Hu, P. Li, G.A. Luo, Plasma esterified and non-esterified fatty acids metabolic profiling using gas-chromatography mass spectrometry and its application in the study of diabetic mellitus and diabetic nephropathy. Anal. Chim. Acta. 689, 85–91 (2011)

    Article  CAS  PubMed  Google Scholar 

  19. Y. Lu, J. Cheng, L. Chen, C. Li, G. Chen, L. Gui, B. Shen, Q. Zhang, Endoplasmic reticulum stress involved in high-fat diet and palmitic acid-induced vascular damages and fenofibrate intervention. Biochem. Biophys. Res. Commun. 458, 1–7 (2015)

    Article  CAS  PubMed  Google Scholar 

  20. L.D. Williams, G.A. Burdock, J.A. Edwards, M. Beck, J. Bausch, Safety studies conducted on high-purity transresveratrol in experimental animals. Food. Chem. Toxicol. 47, 2170–2182 (2009)

    Article  CAS  PubMed  Google Scholar 

  21. M.T. Macarulla, G. Alberdi, S. Gómez, I. Tueros, C. Bald, V.M. Rodríguez, J.A. Martínez, M.P. Portillo, Effects of different doses of resveratrol on body fat and serum parameters in rats fed a hypercaloric diet. J. Physiol. Biochem. 65, 369–376 (2009)

    Article  CAS  PubMed  Google Scholar 

  22. A. Dal-Pan, S. Blanc, E. Aujard, Resveratrol suppresses body mass gain in a seasonal non-human primate model of obesity. BMC. Physiol. 10, 11 (2010)

    Article  PubMed  PubMed Central  Google Scholar 

  23. S. Timmers, E. Konings, L. Bilet, R.H. Houtkooper, T. van de Weijer, G.H. Goossens, J. Hoeks, S. van der Krieken, D. Ryu, S. Kersten, E. Moonen-Kornips, M.K. Hesselink, I. Kunz, V.B. Schrauwen-Hinderling, E.E. Blaak, J. Auwerx, P. Schrauwen, Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profiles in obese humans. Cell. Metab. 14, 612–622 (2011)

    Article  CAS  PubMed  Google Scholar 

  24. Y. Jimenez-Gomez, J.A. Mattison, K.J. Pearson, A. Martin-Montalvo, H.H. Palacios, A.M. Sossong, T.M. Ward, C.M. Younts, K. Lewis, J.S. Allard, D.L. Longo, J.P. Belman, M.M. Malagon, P. Navas, M. Sanghvi, R. Moaddel, E.M. Tilmont, R.L. Herbert, C.H. Morrell, J.M. Egan, J.A. Baur, L. Ferrucci, J.S. Bogan, M. Bernier, R. de Cabo, Resveratrol improves adipose insulin signaling and reduces the inflammatory response in adipose tissue of rhesus monkeys on high-fat, high-sugar diet. Cell. Metab. 18, 533–545 (2013)

    Article  CAS  PubMed  Google Scholar 

  25. J. Olholm, S.K. Paulsen, K.B. Cullberg, B. Richelsen, S.B. Pedersen, Anti-inflammatory effect of resveratrol on adipokine expression and secretion in human adipose tissue explant. Int. J. Obes. 34, 1546–1553 (2010)

    Article  CAS  Google Scholar 

  26. Z.E. Floyd, Z.Q. Wang, G. Kilroy, W.T. Cefalu, Modulation of peroxisome proliferator activated receptor gamma stability and transcriptional activity in adipocytes by resveratrol. Metabolism. 57, S32–S38 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. G. Scapagnini, S. Davinelli, T. Kaneko, G. Koverech, A. Koverech, E.J. Calabrese, V. Calabrese, Dose response biology of resveratrol in obesity. J. Cell. Commun. Signal. 8, 385–391 (2014)

    Article  PubMed  PubMed Central  Google Scholar 

  28. J. Mercader, A. Palou, M.L. Bonet, Resveratrol enhances fatty acid oxidation capacity and reduces resistin and Retinol-Binding Protein 4 expression in white adipocytes. J. Nutr. Biochem. 22, 828–834 (2011)

    Article  CAS  PubMed  Google Scholar 

  29. U. Ozcan, Q. Cao, E. Yilmaz, A.H. Lee, N.N. Iwakoshi, E. Ozdelen, G. Tuncman, C. Görgün, L.H. Glimcher, G.S. Hotamisligil, Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 306, 457–461 (2004)

    Article  PubMed  Google Scholar 

  30. W. Guo, S. Wong, W. Xie, T. Lei, Z. Luo, Palmitate modulates intracellular signaling, induces endoplasmic reticulum stress, and causes apoptosis in mouse 3T3-L1 and rat primary preadipocytes. Am. J. Physiol. Endocrinol. Metab. 293, E576–586 (2007)

    Article  CAS  PubMed  Google Scholar 

  31. S. Li, C. Bouzar, C. Cottet-Rousselle, I. Zagotta, F. Lamarche, M. Wabitsch, M. Tokarska-Schlattner, P. Fischer-Posovszky, U. Schlattner, D.R. Rousseau, esveratrol inhibits lipogenesis of 3T3-L1 and SGBS cells by inhibition of insulin signaling and mitochondrial mass increase. Biochim. Biophys. Acta 1857, 643–652 (2016)

    Article  CAS  PubMed  Google Scholar 

  32. C.S. Andrews, S. Matsuyama, B.C. Lee, J.D. Li, Resveratrol suppresses NTHi-induced inflammation via up-regulation of the negative regulator MyD88 short. Sci. Rep. 6, 34445 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. T. Suganami, J. Nishida, Y. Ogawa, A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor alpha. Arterioscler. Thromb. Vasc. Biol. 25, 2062–2068 (2005)

    Article  CAS  PubMed  Google Scholar 

  34. A. Tchernof, J.P. Després, Pathophysiology of human visceral obesity: an update. Physiol. Rev. 93, 359–404 (2013)

    Article  CAS  PubMed  Google Scholar 

  35. J.S. Burrill, E.K. Long, B. Reilly, Y. Deng, I.M. Armitage, P.E. Scherer, D.A. Bernlohr, Inflammation and ER stress regulate branched-chain amino acid uptake and metabolism in adipocytes. Mol. Endocrinol. 29, 411–420 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Z.M. Lv, Q. Wang, Y.H. Chen, S.H. Wang, D.Q. Huang, Resveratrol attenuates inflammation and oxidative stress in epididymal white adipose tissue: implications for its involvement in improving steroidogenesis in diet-induced obese mice. Mol. Reprod. Dev. 82, 321–328 (2015)

    Article  CAS  PubMed  Google Scholar 

  37. E. Melloni, G. Zauli, C. Celeghini, I. Volpi, P. Secchiero, Release of a specific set of proinflammatory adipokines by differentiating 3T3-L1 cells. Nutrition. 1, 332–327 (2013)

    Article  Google Scholar 

  38. K.D. McCall, D. Holliday, E. Dickerson, B. Wallace, A.L. Schwartz, C. Schwartz, C.J. Lewis, L.D. Kohn, F.L. Schwartz, Phenylmethimazole blocks palmitate-mediated induction of inflammatory cytokine pathways in 3T3L1 adipocytes and RAW 264.7 macrophages. J. Endocrinol. 207, 343–353 (2010)

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study was funded by research grants from Anhui Natural Science Foundation of China (1308085MH154 and 1608085MH208, 1608085QH205) and a special foundation of the National TCM Clinical Research Base (JDZX2015129).

Author information

Author notes

    Authors and Affiliations

    1. Clinical Laboratory, Anhui Provincial Hospital, Hefei, Anhui, 230001, China

      Li Chen

    2. Endocrinology Department, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, China

      Ting Wang, Nuojin Wang, Fang Dai & Qiu Zhang

    3. Department of Chemistry, Anhui Medical University, Hefei, Anhui, 230032, China

      Guanjun Chen

    4. The Comprehensive Laboratory, Anhui Medical University, Hefei, Anhui, 230032, China

      Li Gui & Yunxia Lu

    5. Department of Endocrinology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui, 230032, China

      Zhaohui Fang

    6. Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui, 230031, China

      Yunxia Lu

    Authors
    1. Li Chen
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Ting Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Guanjun Chen
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Nuojin Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Li Gui
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Fang Dai
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Zhaohui Fang
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Qiu Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Yunxia Lu
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Yunxia Lu.

    Ethics declarations

    Conflict of interest

    The authors state no conflict of interest. The authors alone are responsible for the content and writing of this paper.

    Ethical approval

    All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

    Additional information

    Li Chen and Ting Wang contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Chen, L., Wang, T., Chen, G. et al. Influence of resveratrol on endoplasmic reticulum stress and expression of adipokines in adipose tissues/adipocytes induced by high-calorie diet or palmitic acid. Endocrine 55, 773–785 (2017). https://doi.org/10.1007/s12020-016-1212-2

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s12020-016-1212-2

    Keywords

    Search

    Navigation