Skip to main content

Advertisement

SpringerLink
Log in

Dose response biology of resveratrol in obesity

  • RESEARCH ARTICLE
  • Published:
Journal of Cell Communication and Signaling Aims and scope

Abstract

Obesity is a major health problem throughout the world, and it is increasing both in prevalence and severity. Pharmaceutical approaches developed for the treatment of obesity, despite short-term benefits, often are associated with rebound weight gain after the cessation of drug use and serious side effects deriving from the medication can occur. Resveratrol has been well recognized as an anti-obesity substance for its lipid-lowering function as well as calorie-restriction effect. This polyphenol induces hormetic dose responses in a wide range of biological models, affecting numerous endpoints of biomedical and therapeutic significance. From an hormetic standpoint, we will discuss the potential relevance of resveratrol in the management of obesity and related comorbid conditions, emphasizing its ability to control simultaneously various pathological mechanisms associated with obesity.

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

Similar content being viewed by others

Abbreviations

(CR):

Calorie restriction

(WAT):

White adipose tissue

(NF-kβ):

Nuclear factor- kβ

(SIRT-1):

Sirtuin-1

(AMPK):

Adenosine monophosphate activated protein kinase

(FABP4):

Fatty acid binding protein 4

(MCP-1):

Monocyte chemoattractant protein-1

(LPL):

Lipoprotein lipase

(IL)-:

Interleukin

(FOXO):

Forkhead Box O

(MMP):

Metalloproteinase

(SREBP-1c):

Sterol regulatory element binding protein-1c

(TNF-α):

Tumor necrosis factor-alpha

(FAS):

Fatty acid synthase

(C/EBPα):

CCAAT/enhancer binding protein α

(PPARγ):

Peroxisome proliferator-activated receptor-γ

(PGC-1α):

Peroxisome proliferator-activated receptor γ coactivator-1α.

References

  • Almeida L, Vaz-da-Silva M, Falcão A, Soares E, Costa R, Loureiro AI, Fernandes-Lopes C, Rocha JF, Nunes T, Wright L, Soares-da-Silva P (2009) Pharmacokinetic and safety profile of trans-resveratrol in a rising multiple-dose study in healthy volunteers. Mol Nutr Food Res 53:7–15

    Article  Google Scholar 

  • Avogaro A, de Kreutzenberg SV (2005) Mechanisms of endothelial dysfunction in obesity. Clin Chim Acta 360:9–26

    Article  CAS  PubMed  Google Scholar 

  • Barger JL (2013) An adipocentric perspective of resveratrol as a calorie restriction mimetic. Ann N Y Acad Sci 1290:122–129

    Article  CAS  PubMed  Google Scholar 

  • Barger JL, Kayo T, Vann JM, Arias EB, Wang J, Hacker TA, Wang Y, Raederstorff D, Morrow JD, Leeuwenburgh C, Allison DB, Saupe KW, Cartee GD, Weindruch R, Prolla TA (2008) PLoS ONE 3:e2264

    Article  PubMed Central  PubMed  Google Scholar 

  • Barrajón-Catalán E, Herranz-López M, Joven J, Segura-Carretero A, Alonso-Villaverde C, Menéndez JA, Micol V (2014) Molecular promiscuity of plant polyphenols in the management of age-related diseases: far beyond their antioxidant properties. Adv Exp Med Biol 824:141–159

    Article  PubMed  Google Scholar 

  • Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444:337–342

    Article  CAS  PubMed  Google Scholar 

  • Blackburn GL, Miller D, Chan S (1997) Pharmaceutical treatment of obesity. Nurs Clin North Am 32:831–838

    CAS  PubMed  Google Scholar 

  • Bracale R, Petroni ML, Davinelli S, Bracale U, Scapagnini G, Carruba MO, Nisoli E (2014) Muscle uncoupling protein 3 expression is unchanged by chronic ephedrine/caffeine treatment: results of a double blind, randomised clinical trial in morbidly obese females. PLoS ONE 9:e98244

    Article  PubMed Central  PubMed  Google Scholar 

  • 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 AJ, 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 70:9003–9011

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Calabrese EJ, Mattson MP, Calabrese V (2010a) Dose response biology: the case of resveratrol. Hum Exp Toxicol 29:1034–1037

    Article  CAS  PubMed  Google Scholar 

  • Calabrese V, Cornelius C, Dinkova-Kostova AT, Calabrese EJ, Mattson MP (2010b) Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders. Antioxid Redox Signal 13:1763–1811

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Calabrese V, Cornelius C, Dinkova-Kostova AT, Iavicoli I, Di Paola R, Koverech A, Cuzzocrea S, Rizzarelli E, Calabrese EJ (2012) Cellular stress responses, hormetic phytochemicals and vitagenes in aging and longevity. Biochim Biophys Acta 1822:753–783

    Article  CAS  PubMed  Google Scholar 

  • Carrizzo A, Forte M, Damato A, Trimarco V, Salzano F, Bartolo M, Maciag A, Puca AA, Vecchione C (2013) Antioxidant effects of resveratrol in cardiovascular, cerebral and metabolic diseases. Food Chem Toxicol 61:215–226

    Article  CAS  PubMed  Google Scholar 

  • Catterall F, Souquet JM, Cheynier V, de Pascual-Teresa S, Santos-Buelga C, Clifford MN, Ioannides C (2000) Differential modulation of the genotoxicity of food carcinogens by naturally occurring monomeric and dimeric polyphenolics. Environ Mol Mutagen 35:86–98

    Article  CAS  PubMed  Google Scholar 

  • Fuentes E, Fuentes F, Vilahur G, Badimon L, Palomo I (2013) Mechanisms of chronic state of inflammation as mediators that link obese adipose tissue and metabolic syndrome. Mediat Inflamm 2013:136584

    Google Scholar 

  • Gómez-Zorita S, Fernández-Quintela A, Lasa A, Hijona E, Bujanda L, Portillo MP (2013) Effects of resveratrol on obesity-related inflammation markers in adipose tissue of genetically obese rats. Nutrition 29:1374–1380

    Article  PubMed  Google Scholar 

  • González-Castejón M, Rodriguez-Casado A (2011) Dietary phytochemicals and their potential effects on obesity: a review. Pharmacol Res 64:438–455

    Article  PubMed  Google Scholar 

  • Jeon BT, Jeong EA, Shin HJ, Lee Y, Lee DH, Kim HJ, Kang SS, Cho GJ, Choi WS, Roh GS (2012) Resveratrol attenuates obesity-associated peripheral and central inflammation and improves memory deficit in mice fed a high-fat diet. Diabetes 61:1444–1454

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kang L, Heng W, Yuan A, Baolin L, Fang H (2010) Resveratrol modulates adipokine expression and improves insulin sensitivity in adipocytes: Relative to inhibition of inflammatory responses. Biochimie 92:789–796

    Article  PubMed  Google Scholar 

  • Kang NE, Ha AW, Kim JY, Kim WK (2012) Resveratrol inhibits the protein expression of transcription factors related adipocyte differentiation and the activity of matrix metalloproteinase in mouse fibroblast 3 T3-L1 preadipocytes. Nutr Res Pract 6:499–504

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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  PubMed  Google Scholar 

  • Lee J, Jo DG, Park D, Chung HY, Mattson MP (2014) Adaptive cellular stress pathways as therapeutic targets of dietary phytochemicals: focus on the nervous system. Pharmacol Rev 66:815–868

    Article  CAS  PubMed  Google Scholar 

  • Mattson MP, Cheng A (2006) Neurohormetic phytochemicals: Low-dose toxins that induce adaptive neuronal stress responses. Trends Neurosci 29:632–639

    Article  CAS  PubMed  Google Scholar 

  • Mennen LI, Walker R, Bennetau-Pelissero C, Scalbert A (2005) Risks and safety of polyphenol consumption. Am J Clin Nutr 81:326S–329S

    CAS  PubMed  Google Scholar 

  • Naderali EK (2009) Obesity and cardiovascular dysfunction: a role for resveratrol? Obes Res Clin Pract 3:45–52

    Article  Google Scholar 

  • Panickar KS (2013) Effects of dietary polyphenols on neuroregulatory factors and pathways that mediate food intake and energy regulation in obesity. Mol Nutr Food Res 57:34–47

    Article  CAS  PubMed  Google Scholar 

  • Pervaiz S, Holme AL (2009) Resveratrol: its biologic targets and functional activity. Antioxid Redox Signal 11:2851–2897

    Article  CAS  PubMed  Google Scholar 

  • Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, Machado De Oliveira R, Leid M, McBurney MW, Guarente L (2004) Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature 429:771–776

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, Eckel RH (2006) Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss. Arterioscler Thromb Vasc Biol 26:968–976

    Article  CAS  PubMed  Google Scholar 

  • Poulsen MM, Jørgensen JO, Jessen N, Richelsen B, Pedersen SB (2013a) Resveratrol in metabolic health: an overview of the current evidence and perspectives. Ann N Y Acad Sci 1290:74–82

    Article  CAS  PubMed  Google Scholar 

  • Poulsen MM, Vestergaard PF, Clasen BF, Radko Y, Christensen LP, Stødkilde-Jørgensen H, Møller N, Jessen N, Pedersen SB, Jørgensen JO (2013b) High-dose resveratrol supplementation in obese men: an investigator-initiated, randomized, placebo-controlled clinical trial of substrate metabolism, insulin sensitivity, and body composition. Diabetes 62:1186–1195

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Price NL, Gomes AP, Ling AJ, Duarte FV, Martin-Montalvo A, North BJ, Agarwal B, Ye L, Ramadori G, Teodoro JS, Hubbard BP, Varela AT, Davis JG, Varamini B, Hafner A, Moaddel R, Rolo AP, Coppari R, Palmeira CM, de Cabo R, Baur JA, Sinclair DA (2012) SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab 15:675–690

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Quideau S, Deffieux D, Douat-Casassus C, Pouységu L (2011) Plant polyphenols: chemical properties, biological activities, and synthesis. Angew Chem Int Ed Engl 50:586–621

    Article  CAS  PubMed  Google Scholar 

  • Rayalam S, Yang JY, Ambati S, Della-Fera MA, Baile CA (2008) Resveratrol induces apoptosis and inhibits adipogenesis in 3 T3-L1 adipocytes. Phytother Res 22:1367–1371

    Article  CAS  PubMed  Google Scholar 

  • Sun Y, Li J, Xiao N, Wang M, Kou J, Qi L, Huang F, Liu B, Liu K (2014) Pharmacological activation of AMPK ameliorates perivascular adipose/endothelial dysfunction in a manner interdependent on AMPK and SIRT1. Pharmacol Res 89:19–28

    Article  CAS  PubMed  Google Scholar 

  • Tang PC, Ng YF, Ho S, Gyda M, Chan SW (2014) Resveratrol and cardiovascular health - Promising therapeutic or hopeless illusion? Pharmacol Res pii:S1043-6618(14)00138-8

  • Timmers S, Konings E, Bilet L, Houtkooper RH, van de Weijer T, Goossens GH, Hoeks J, van der Krieken S, Ryu D, Kersten S, Moonen-Kornips E, Hesselink MK, Kunz I, Schrauwen-Hinderling VB, Blaak EE, 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 14:612–622

    Article  CAS  PubMed  Google Scholar 

  • Tomé-Carneiro J, Gonzálvez M, Larrosa M, Yáñez-Gascón MJ, García-Almagro FJ, Ruiz-Ros JA, Tomás-Barberán FA, García-Conesa MT, Espín JC (2013) Grape resveratrol increases serum adiponectin and downregulates inflammatory genes in peripheral blood mononuclear cells: a triple-blind, placebo-controlled, one-year clinical trial in patients with stable coronary artery disease. Cardiovasc Drugs Ther 27:37–48

    Article  PubMed Central  PubMed  Google Scholar 

  • 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  PubMed  Google Scholar 

  • Wellman NS, Friedberg B (2002) Causes and consequences of adult obesity: health, social and economic impacts in the United States. Asia Pac J Clin Nutr Suppl 8:705–709

    Article  Google Scholar 

  • Wong RH, Howe PR, Buckley JD, Coates AM, Kunz I, Berry NM (2011) Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure. Nutr Metab Cardiovasc Dis 21:851–856

    Article  CAS  PubMed  Google Scholar 

  • Yoshino J, Conte C, Fontana L, Mittendorfer B, Imai S, Schechtman KB, Gu C, Kunz I, Rossi Fanelli F, Patterson BW, Klein S (2013) Resveratrol supplementation does not improve metabolic function in nonobese women with normal glucose tolerance. Cell Metab 16:658–664

    Article  Google Scholar 

  • Zhang XH, Huang B, Choi SK, Seo JS (2012) Anti-obesity effect of resveratrol-amplified grape skin extracts on 3 T3-L1 adipocytes differentiation. Nutr Res Pract 6:286–293

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy

    Giovanni Scapagnini & Sergio Davinelli

  2. Inter-University Consortium “SannioTech”, Benevento, Italy

    Giovanni Scapagnini & Vittorio Calabrese

  3. Department of Neurology, Oregon Health & Science University, Portland, OR, USA

    Taku Kaneko

  4. Department of Biomedical Sciences, University of Catania, Catania, Italy

    Guido Koverech, Angela Koverech & Vittorio Calabrese

  5. Environmental Health Sciences Division, School of Public Health, University of Massachusetts, Amherst, MA, USA

    Edward J. Calabrese

Authors
  1. Giovanni Scapagnini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sergio Davinelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Taku Kaneko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guido Koverech
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Angela Koverech
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Edward J. Calabrese
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Vittorio Calabrese
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vittorio Calabrese.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Scapagnini, G., Davinelli, S., Kaneko, T. et al. Dose response biology of resveratrol in obesity. J. Cell Commun. Signal. 8, 385–391 (2014). https://doi.org/10.1007/s12079-014-0257-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12079-014-0257-3

Keywords

Search

Navigation