Journal of Physiology and Biochemistry

, Volume 69, Issue 3, pp 585–593 | Cite as

Resveratrol directly affects in vitro lipolysis and glucose transport in human fat cells

  • Saioa Gomez-Zorita
  • Karine Tréguer
  • Josep Mercader
  • Christian CarpénéEmail author
Original Paper


Resveratrol is a naturally occurring polyphenol found in many dietary sources and red wine. Recognized as a cancer chemoprevention agent, an anti-inflammatory factor and an antioxidant molecule, resveratrol has been proposed as a potential anti-obesity compound and to be beneficial in diabetes. Most of the studies demonstrating the anti-adipogenic action of resveratrol were performed as long-term treatments on cultured preadipocytes. The aim of this study was to analyse the acute effects of resveratrol on glucose uptake and lipolysis in human mature adipocytes. Samples of subcutaneous abdominal adipose tissue were obtained from overweight humans and immediately digested by liberase. Fat cells were incubated (from 45 min to 4 h) with resveratrol 1 μM–1 mM. Then, glycerol release or hexose uptake was determined. Regarding lipolysis, the significant effects of resveratrol were found at 100 μM, consisting in a facilitation of isoprenaline stimulation and an impairment of insulin antilipolytic action. At 1 and 10 μM, resveratrol only tended to limit glucose uptake. Resveratrol 100 μM did not change basal glucose uptake but impaired its activation by insulin or by benzylamine. This inhibition was not found with other antioxidants. Such impairment of glucose uptake activation in fat cells may led to a reduced availability of glycerol phosphate and then to a decreased triacylglycerol assembly. Therefore, resveratrol increased triacylglycerol breakdown triggered by β-adrenergic activation and impaired lipogenesis. Consequently, our data indicate that resveratrol can be considered as limiting fat accumulation in human fat cells and further support its use for the mitigation of obesity.


Resveratrol Benzylamine Human adipocytes Antioxidants Dietary supplements 



This work was partly supported by Communauté de Travail des Pyrénées and the DIOMED project (INTERREG IVB-SUDOE-FEDER, SOE1/P1/E178). The authors express gratitude to Simon Rascalou, Sarah Canteiro and Sandra Grès for their help. They also acknowledge Philippe Valet (Univ. Paul Sabatier, Toulouse, France) and Maria P. Portillo (Univ. of Pais Vasco, Vitoria, Spain) for their respective knowledge on human adipocyte biology and dietary diphenolic compounds and the staff of Plastic Surgery Dpt. of Rangueil Hospital for facilitating access to their post-surgical wastes.


  1. 1.
    Ajmo JM, Liang X, Rogers CQ, Pennock B, You M (2008) Resveratrol alleviates alcoholic fatty liver in mice. Am J Physiol Gastrointest Liver Physiol 295:G833–G842PubMedCrossRefGoogle Scholar
  2. 2.
    Akagawa M, Suyama K (2001) Amine oxidase-like activity of polyphenols. Mechanism and properties. Eur J Biochem 268:1953–1963PubMedCrossRefGoogle Scholar
  3. 3.
    Alberdi G, Rodríguez VM, Miranda J, Macarulla MT, Arias N, Andrés-Lacueva C, Portillo MP (2011) Changes in white adipose tissue metabolism induced by resveratrol in rats. Nutr Metab (Lond) 8:29CrossRefGoogle Scholar
  4. 4.
    Arias N, Macarulla MT, Aguirre L, Martínez-Castaño MG, Gómez-Zorita S, Miranda J, Martínez JA, Portillo MP (2011) The combination of resveratrol and conjugated linoleic acid is not useful in preventing obesity. J Physiol Biochem 67:471–477PubMedCrossRefGoogle Scholar
  5. 5.
    Atgié C, Hadj-Sassi L, Bukowiecki L, Mauriège P (2009) High lipolytic activity and dyslipidemia in a spontaneous hypertensive/NIH corpulent (SHR/N-cp) rat: a genetic model of obesity and type 2 diabetes mellitus. J Physiol Biochem 65:33–42PubMedCrossRefGoogle Scholar
  6. 6.
    Atgié C, Sauvant P, Ambid L, Carpéné C (2009) Possible mechanisms of weight loss of Siberian hamsters (Phodopus sungorus sungorus) exposed to short photoperiod. J Physiol Biochem 65:377–386PubMedCrossRefGoogle Scholar
  7. 7.
    Baile CA, Yang JY, Rayalam S, Hartzell DL, Lai CY, Andersen C, Della-Fera MA (2011) Effect of resveratrol on fat mobilization. Ann N Y Acad Sci 1215:40–47PubMedCrossRefGoogle Scholar
  8. 8.
    Breen DM, Sanli T, Giacca A, Tsiani E (2008) Stimulation of muscle cell glucose uptake by resveratrol through sirtuins and AMPK. Biochem Biophys Res Commun 374:117–122PubMedCrossRefGoogle Scholar
  9. 9.
    Brown VA, Patel KR, Viskaduraki M, Crowell JA, Perloff M, Booth TD, Vasilinin G, Sen A, Schinas AM, Piccirilli G, Brown K, Steward WP, Gescher A, Brenner DE (2010) Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis. Cancer Res 70:9003–9011PubMedCrossRefGoogle Scholar
  10. 10.
    Costa CS, Rohden F, Hammes TO, Margis R, Bortolotto JW, Padoin AV, Mottin CC, Guaragna RM (2011) Resveratrol upregulated SIRT1, FOXO1, and adiponectin and downregulated PPARγ1-3 mRNA expression in human visceral adipocytes. Obes Surg 21:356–361CrossRefGoogle Scholar
  11. 11.
    Fischer-Posovszky P, Kukulus V, Tews D, Unterkircher T, Debatin KM, Fulda S, Wabitsch M (2010) Resveratrol regulates human adipocyte number and function in a Sirt1-dependent manner. Am J Clin Nutr 92:5–15PubMedCrossRefGoogle Scholar
  12. 12.
    Floyd ZE, Wang ZQ, Kilroy G, Cefalu WT (2008) Modulation of peroxisome proliferator-activated receptor gamma stability and transcriptional activity in adipocytes by resveratrol. Metabolism 57:S32–S38PubMedCrossRefGoogle Scholar
  13. 13.
    Gómez-Zorita S, Fernández-Quintela A, Macarulla MT, Aguirre L, Hijona E, Bujanda L, Milagro F, Martínez JA, Portillo MP (2012) Resveratrol attenuates steatosis in obese Zucker rats by decreasing fatty acid availability and reducing oxidative stress. Br J Nutr 107:202–210PubMedCrossRefGoogle Scholar
  14. 14.
    Grès S, Bour S, Valet P, Carpéné C (2012) Benzylamine antihyperglycemic effect is abolished by AOC3 gene invalidation in mice but not rescued by semicarbazide-sensitive amine oxidase expression under the control of aP2 promoter. J Physiol Biochem 68:651–662PubMedCrossRefGoogle Scholar
  15. 15.
    Iffiú-Soltész Z, Mercader J, Daviaud D, Boucher J, Carpéné C (2011) Increased primary amine oxidase expression and activity in white adipose tissue of obese and diabetic db−/− mice. J Neural Transm 118:1071–1077PubMedCrossRefGoogle Scholar
  16. 16.
    Iglesias-Osma MC, Bour S, Garcia-Barrado MJ, Visentin V, Pastor MF, Testar X, Marti L, Enrique-Tarancon G, Valet P, Moratinos J, Carpéné C (2005) Methylamine but not mafenide mimics insulin-like actvity of the semicarbazide-sensitive amine oxidase-substrate benzylamine on glucose tolerance and on human adipocyte metabolism. Pharmacol Res 52:475–484PubMedCrossRefGoogle Scholar
  17. 17.
    Kang W, Hong HJ, Guan J, Kim DG, Yang EJ, Koh G, Park D, Han CH, Lee YJ, Lee DH (2012) Resveratrol improves insulin signaling in a tissue-specific manner under insulin-resistant conditions only: in vitro and in vivo experiments in rodents. Metabolism 61:424–433PubMedCrossRefGoogle Scholar
  18. 18.
    Kennedy A, Overman A, Lapoint K, Hopkins R, West T, Chuang CC, Martinez K, Bell D, McIntosh M (2009) Conjugated linoleic acid-mediated inflammation and insulin resistance in human adipocytes are attenuated by resveratrol. J Lipid Res 50:225–232PubMedCrossRefGoogle Scholar
  19. 19.
    Krawczyk SA, Haller JF, Ferrante T, Zoeller RA, Corkey BE (2012) Reactive oxygen species facilitate translocation of hormone sensitive lipase to the lipid droplet during lipolysis in human differentiated adipocytes. PLoS One 7:e34904PubMedCrossRefGoogle Scholar
  20. 20.
    Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127:1109–1122PubMedCrossRefGoogle Scholar
  21. 21.
    Lasa A, Churruca I, Eseberri I, Andrés-Lacueva C, Portillo MP (2012) Delipidating effect of resveratrol metabolites in 3T3-L1 adipocytes. Mol Nutr Food Res 56:1559–1568PubMedCrossRefGoogle Scholar
  22. 22.
    Lasa A, Schweiger M, Kotzbeck P, Churruca I, Simón E, Zechner R, Del Puy PM (2012) Resveratrol regulates lipolysis via adipose triglyceride lipase. J Nutr Biochem 23:379–384PubMedCrossRefGoogle Scholar
  23. 23.
    Maraculla MT, Alberdi G, Gomez S, Tueros I, Bald C, Rodriguez VM, Martinez JA, Portillo MP (2009) Effects of different doses of resveratrol on body fat and serum parameters in rats fed a hypercaloric diet. J Physiol Biochem 65:369–376CrossRefGoogle Scholar
  24. 24.
    Mercader J, Iffiú-Soltesz Z, Brenachot X, Földi A, Dunkel P, Balogh B, Attané C, Valet P, Mátyus P, Carpéné C (2010) SSAO substrates exhibiting insulin-like effects in adipocytes as a promising treatment option for metabolic disorders. Future Med Chem 2:1735–1749PubMedCrossRefGoogle Scholar
  25. 25.
    Mercader J, Palou A, Bonet ML (2011) Resveratrol enhances fatty acid oxidation capacity and reduces resistin and retinol-binding protein 4 expression in white adipocytes. J Nutr Biochem 22:828–834PubMedCrossRefGoogle Scholar
  26. 26.
    Mercader J, Wanecq E, Chen J, Carpéné C (2011) Isopropylnorsynephrine is a stronger lipolytic agent in human adipocytes than synephrine and other amines present in Citrus aurantium. J Physiol Biochem 67:443–452PubMedCrossRefGoogle Scholar
  27. 27.
    Olholm J, Paulsen SK, Cullberg KB, Richelsen B, Pedersen SB (2010) Anti-inflammatory effect of resveratrol on adipokine expression and secretion in human adipose tissue explants. Int J Obes (Lond) 34:1546–1553CrossRefGoogle Scholar
  28. 28.
    Park HJ, Yang JY, Ambati S, Della-Fera MA, Hausman DB, Rayalam S, Baile CA (2008) Combined effects of genistein, quercetin, and resveratrol in human and 3T3-L1 adipocytes. J Med Food 11:773–783PubMedCrossRefGoogle Scholar
  29. 29.
    Pedersen SB, Ølholm J, Paulsen SK, Bennetzen MF, Richelsen B (2008) Low Sirt1 expression, which is upregulated by fasting, in human adipose tissue from obese women. Int J Obes (Lond) 32:1250–1255CrossRefGoogle Scholar
  30. 30.
    Rayalam S, Yang J-Y, Ambati S, Della-Fera MA, Baile CA (2008) Resveratrol induces apoptosis and inhibits adipogenesis in 3T3-L1 adipocytes. Phytother Res 22:1367–1371PubMedCrossRefGoogle Scholar
  31. 31.
    Rivera L, Moron R, Zarzuelo A, Galisteo M (2009) Long-term resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats. Biochem Pharmacol 77:1053–1063PubMedCrossRefGoogle Scholar
  32. 32.
    Serrano J, Jové M, Boada J, Bellmunt MJ, Pamplona R, Portero-Otín M (2009) Dietary antioxidants interfere with Amplex Red-coupled-fluorescence assays. Biochem Biophys Res Commun 388:443–449PubMedCrossRefGoogle Scholar
  33. 33.
    Su HC, Hung LM, Chen JK (2006) Resveratrol, a red wine antioxidant, possesses an insulin-like effect in streptozotocin-induced diabetic rats. Am J Physiol Endocrinol Metab 290:E1339–E1346PubMedCrossRefGoogle Scholar
  34. 34.
    Szkudelska K, Nogowski L, Szkudelski T (2009) Resveratrol, a naturally occurring diphenolic compound, affects lipogenesis, lipolysis and antilipolytic action of insulin in isolated rat adipocytes. J Steroid Biochem Mol Biol 113:17–24PubMedCrossRefGoogle Scholar
  35. 35.
    Szkudelska K, Nogowski L, Szkudelski T (2011) Resveratrol and genistein as adenosine triphosphate-depleting agents in fat cells. Metabolism 60:720–729PubMedCrossRefGoogle Scholar
  36. 36.
    Szkudelski T, Szkudelska K (2011) Anti-diabetic effects of resveratrol. Ann N Y Acad Sci 1215:34–39PubMedCrossRefGoogle Scholar
  37. 37.
    Timmers S, Konings E, Bilet L, Houtkooper RH, van de Weijer T, Goossens G, Hoeks J, van der Krieken S, Ryu D, Kersten S, Moonen-Kornips E, Hesselink M, Kunz I, Schrauwen-Hinderling V, Blaak E, Auwerx J, Schrauwen P (2011) Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab 14:612–622PubMedCrossRefGoogle Scholar
  38. 38.
    Wanecq E, Prévot D, Carpéné C (2009) Lack of direct insulin-like action of visfatin/Nampt/PBEF1 in human adipocytes. J Physiol Biochem 65:351–360PubMedCrossRefGoogle Scholar
  39. 39.
    Yang JY, Della-Fera MA, Rayalam S, Ambati S, Hartzell DL, Park HJ, Baile CA (2008) Enhanced inhibition of adipogenesis and induction of apoptosis in 3T3-L1 adipocytes with combinations of resveratrol and quercetin. Life Sci 82:1032–1039PubMedCrossRefGoogle Scholar
  40. 40.
    Yoshino J, Conte C, Fontana L, Mittendorfer B, Imai SI, Schechtman KB, Gu C, Kunz I, Fanelli FR, Patterson BW, Klein S (2012) Resveratrol supplementation does not improve metabolic function in nonobese women with normal glucose tolerance. Cell Metab 16:658–664PubMedCrossRefGoogle Scholar

Copyright information

© University of Navarra 2013

Authors and Affiliations

  • Saioa Gomez-Zorita
    • 1
  • Karine Tréguer
    • 2
  • Josep Mercader
    • 2
  • Christian Carpéné
    • 2
    Email author
  1. 1.I2MC, Université de Toulouse, UPSToulouseFrance
  2. 2.Institut des Maladies Métaboliques et CardiovasculairesInstitut National de la Santé et de la Recherche Médicale (INSERM U1048)Toulouse Cedex 4France

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