Skip to main content
Log in

A high-fat high-sucrose diet affects the long-term metabolic fate of grape proanthocyanidins in rats

  • Original Contribution
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

Polyphenol metabolites are key mediators of the biological activities of polyphenols. This study aimed to evaluate the long-term effects of a high-fat high-sucrose (HFHS) diet on the metabolism of proanthocyanidins from grape seed extract (GSE).

Methods

Adult female Wistar–Kyoto rats were fed a standard (STD) or HFHS diet supplemented or not with GSE for 16 weeks. PA metabolites were determined by targeted HPLC–MS/MS analysis.

Results

A lower concentration of total microbial-derived PA metabolites was present in urine and the aqueous fraction of faeces in the HFHS + GSE group than in the STD + GSE group. In contrast, a tendency towards the formation of conjugated (epi)catechin metabolites in the HFHS + GSE group was observed.

Conclusions

These results show that a HFHS diet significantly modifies PA metabolism, probably via: (1) a shift in microbial communities not counteracted by the polyphenols themselves; and (2) an up-regulation of hepatic enzymes.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

EC:

(Epi)catechin

EGC:

(Epi)gallocatechin

Gluc:

Glucuronyl group

GSE:

Grape seed extract

HFHS:

High-fat high-sucrose diet

Me:

Methyl group

MetS:

Metabolic syndrome

MRM:

Multiple reaction monitoring

MS:

Mass spectrometry

PA:

Proanthocyanidin

STD:

Standard

Sulf:

Sulphate group

References

  1. Alberti KGMM, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James PT, Loria CM, Smith SC (2009) Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; National heart, lung, and blood institute; American heart association; World heart federation; International atherosclerosis society; and international association for the study of obesity. Circulation 120:1640–1645

    Article  CAS  Google Scholar 

  2. Grundy SM (2008) Metabolic syndrome pandemic. Arterioscler Thromb Vasc Biol 28:629–636

    Article  CAS  Google Scholar 

  3. Bourgoin F, Bachelard H, Badeau M, Melançon S, Pitre M, Larivière R, Nadeau A (2008) Endothelial and vascular dysfunctions and insulin resistance in rats fed a high-fat, high-sucrose diet. Am J Physiol Heart Circ Physiol 295:1044–1055

    Article  Google Scholar 

  4. Ishimoto T, Lanspa MA, Rivard CJ, Roncal-Jiménez CA, Orlicky DJ, Cicerchi C, McMahan RH, Abdelmalek MF, Rosen HR, Jackman MR et al (2013) High-fat and high-sucrose (western) diet induces steatohepatitis that is dependent on fructokinase. Hepatology 58:1632–1643

    Article  CAS  Google Scholar 

  5. Naderali EK, Williams G (2003) Prolonged endothelial-dependent and -independent arterial dysfunction induced in the rat by short-term feeding with a high-fat, high-sucrose diet. Atherosclerosis 166:253–259

    Article  CAS  Google Scholar 

  6. Sato A, Kawano H, Notsu T, Ohta M, Nakakuki M, Mizuguchi K, Itoh M, Suganami T, Ogawa Y (2010) Antiobesity effect of eicosapentaenoic acid in high-fat/high-sucrose diet-induced obesity: importance of hepatic lipogenesis. Diabetes 59:2495–2504

    Article  CAS  Google Scholar 

  7. Molinar-Toribio E, Pérez-Jiménez J, Ramos-Romero S, Gómez L, Taltavull N, Nogués MR, Adeva A, Jáuregui O, Joglar J, Clapés P et al (2015) d-Fagomine attenuates metabolic alterations induced by a high-energy-dense diet in rats. Food Funct 6:2614–2619

    Article  CAS  Google Scholar 

  8. Mattison JA, Wang M, Bernier M, Zhang J, Park SS, Maudsley S, Ann SS, Santhanam L, Martin B, Faulkners S et al (2014) Resveratrol prevents high fat/sucrose diet-induced central arterial wall inflammation and stiffening in nonhuman primates. Cell Metab 20:183–190

    Article  CAS  Google Scholar 

  9. Serrano J, Puupponen-Pimia R, Dauer A, Aura AM, Saura-Calixto F (2009) Tannins: current knowledge of food sources, intake, bioavailability and biological effects. Mol Nutr Food Res 53:310–329

    Article  Google Scholar 

  10. Bladé C, Arola L, Salvadó MJ (2010) Hypolipidemic effects of proanthocyanidins and their underlying biochemical and molecular mechanisms. Mol Nutr Food Res 54:37–59

    Article  Google Scholar 

  11. Barrett A, Ndou T, Hughey CA, Straut C, Howell A, Dai Z, Zaletunc G (2013) Inhibition of α-amylase and glucoamylase by tannins extracted from cocoa, pomegranates, cranberries, and grapes. J Agric Food Chem 61:1477–1486

    Article  CAS  Google Scholar 

  12. Castell-Auví A, Cedó L, Pallarès V, Blay MT, Pinent M, Motilva MJ, García-Vallés S, Pujadas G, Maechler P, Ardévol A (2012) Procyanidins modify insulinemia by affecting insulin production and degradation. J Nutr Biochem 23:1565–1572

    Article  Google Scholar 

  13. Fraga CG, Galleano M, Verstraeten SV, Oteiza PI (2010) Basic biochemical mechanisms behind the health benefits of polyphenols. Mol Asp Med 31:435–445

    Article  CAS  Google Scholar 

  14. Pan MH, Lai CS, Ho CT (2010) Anti-inflammatory activities of natural flavonoids. Food Funct 1:15–31

    Article  CAS  Google Scholar 

  15. Rodríguez-Mateos A, Vauzour D, Krueger CG, Shanmuganayagam D, Reed J, Calani L (2014) Bioavailability, bioactivity and impact on health of dietary flavonoids and related compounds: an update. Arch Toxicol 88:1803–1853

    Article  Google Scholar 

  16. Williamson G, Clifford MN (2010) Colonic metabolites of berry polyphenols: the missing link to their biological activity? Br J Nutr 104:48–66

    Article  Google Scholar 

  17. Urpí-Sardá M, Llorach R, Khan N, Monagas M, Rotches-Ribalta M, Lamuela-Raventós RM, Estruch R, Tinahones FJ, Andrés-Lacueva C (2010) Effect of milk on the urinary excretion of microbial phenolic acids after cocoa powder consumption in humans. J Agric Food Chem 58:4706–4711

    Article  Google Scholar 

  18. Tulipani S, Martínez-Huélamo M, Rotchés M, Estruch R, Escribano E, Andrés-Lacueva C, Illán M, Lamuela-Raventós RM (2012) Oil matrix effects on plasma exposure and urinary excretion of phenolic compounds from tomato sauces: evidence from a human pilot study. Food Chem 30:581–590

    Article  Google Scholar 

  19. Rodríguez-Mateos A, Cifuentes-Gómez T, González-Salvador I, Ottaviani JI, Schroeter H, Kelm M, Heiss C, Spencer JPE (2015) Influence of age on the absorption, metabolism, and excretion of cocoa flavanols in healthy subjects. Mol Nutr Food Res 59:1504–1512

    Article  Google Scholar 

  20. Aoun M, Michel F, Fouret G, Jullien M, Wrutniak-Cabello C, Ramos J, Cristol JP, Coudray C, Carbonneau MA, Feillet-Coudray C (2010) A polyphenol extract modifies quantity but not quality of liver fatty acid content in high-fat-high-sucrose diet-fed rats: possible implication of the sirtuin pathway. Br J Nutr 104:1760–1770

    Article  CAS  Google Scholar 

  21. Heber D, Zhang Y, Yang J, Ma JE, Henning SM, Li Z (2014) Green tea, black tea, and oolong tea polyphenols reduce visceral fat and inflammation in mice fed high-fat, high-sucrose obesogenic diets. J Nutr 144:1385–1393

    Article  CAS  Google Scholar 

  22. Etxebarría L, Arias N, Boqué N, Macarulla MT, Portillo MP, Martínez JA, Milagro FI (2015) Reshaping faecal gut microbiota composition by the intake of trans-resveratrol and quercetin in high-fat sucrose diet-fed rats. J Nutr Biochem 26:651–660

    Article  Google Scholar 

  23. Dudonné S, Varin TV, Anhê FF, Dubé P, Roy D, Pilon G, Marette A, Levy E, Jacquot C, Urdaci M et al (2015) Modulatory effects of a cranberry extract co-supplementation with Bacillus subtilis CU1 probiotic on phenolic compounds bioavailability and gut microbiota composition in high-fat diet-fed mice. PharmaNutrition 3:89–100

    Article  Google Scholar 

  24. Touriño S, Fuguet E, Vinardell MP, Cascante M, Torres JL (2009) Phenolic metabolites of grape antioxidant dietary fiber in rat urine. J Agric Food Chem 57:11418–11426

    Article  Google Scholar 

  25. Touriño S, Pérez-Jiménez J, Mateos-Martín ML, Fuguet E, Vinardell MP, Cascante M, Torres JL (2011) Metabolites in contact with the rat digestive tract after ingestion of a phenolic-rich dietary fiber matrix. J Agric Food Chem 59:5955–5963

    Article  Google Scholar 

  26. Urpí-Sardá M, Garrido I, Monagas M, Gómez-Cordovés C, Medina-Remón A, Andrés-Lacueva C (2009) Profile of plasma and urine metabolites after the intake of almond [Prunus dulcis (Mill.) D.A. Webb] polyphenols in humans. J Agric Food Chem 57:10134–10142

    Article  Google Scholar 

  27. Monagas M, Urpí-Sardá M, Sánchez-Patán F, Llorach R, Garrido I, Gómez-Cordovés C, Andrés-Lacueva C, Bartolomé B (2010) Insights into the metabolism and microbial transformation of dietary flavan-3ols and the bioactivity of their metabolites. Food Function 1:233–253

    Article  CAS  Google Scholar 

  28. Choy YY, Quifer-Rada P, Holstege DM, Frese SA, Calvert CA, Mills DA, Lamuela-Raventós RM, Waterhouse AL (2014) Phenolic metabolites and substantial microbiome changes in pig feces by ingesting grape seed proanthocyanidins. Food Funct 5:2298–2308

    Article  CAS  Google Scholar 

  29. Vitaglione p, Barone Lumaga R, Ferracane R, Sellitto S, Morelló JR, Requnat Miranda J, Shimoni E, Fogliano V (2012) Human bioavailability of flavanols and phenolic acids from cocoa-nut creams enriched with free or microencapsulated cocoa polyphenols. Br J Nutr 28:1832–1843

    Google Scholar 

  30. Li C, Lee MJ, Sheng S, Meng X, Prabhu S, Winnik B, Huang B, Chung JY, Yan S, Ho CT et al (2000) Structural identification of two metabolites of catechins and their kinetics in human urine and blood after tea ingestion. Chem Res Toxicol 13:177–184

    Article  CAS  Google Scholar 

  31. Meng X, Sang S, Zhu N, Lu H, Sheng S, Lee MJ, Ho CT, Yang CS (2002) Identification and characterization of methylated and ring-fission metabolites of tea catechins formed in humans, mice, and rats. Chem Res Toxicol 15:1042–1050

    Article  CAS  Google Scholar 

  32. Wishart D, Tzur D, Knox C, Eisner R, Guo AC, Young N, Cheng D, Jewell K, Arndt D, Sawhney S et al (2007) HMDB: the human metabolome database. Nucleic Acid Res 35:521–526

    Article  Google Scholar 

  33. Gill CIR, McDougall CJ, Glidewell S, Stewart D, Shen Q, Tuohy K, Dobbin A, Boyd D, Brown D, Haldar S et al (2010) Profiling of phenols in human fecal water after raspberry supplementation. J Agric Food Chem 58:10389–10395

    Article  CAS  Google Scholar 

  34. Scazzocchio B, Vari R, Filesi C, Del Gaudio I, D’Archivio M, Santangelo C, Iacovelli A, Galvano F, Pluchinotta FR, Gioannini C et al (2015) Protocatechuic acid activates key component of insulin signalling pathway mimicking insulin activity. Mol Nutr Food Res 59:1472–1481

    Article  CAS  Google Scholar 

  35. Mora-Cubillos X, Tulipani S, García-Aloy M, Bulló M, Tinahones FJ, Andrés-Lacueva C (2015) Plasma metabolomics biomarkers of mixed nuts exposure inversely correlate with severity of metabolic syndrome. Mol Nutr Food Res 59:2480–2490

    Article  CAS  Google Scholar 

  36. Ramos-Romero S, Molinar-Toribio E, Gómez L, Pérez-Jiménez J, Casado M, Clapés P, Piña B, Torres JL (2014) Effect of d-fagomine on excreted enterobacteria and weight gain in rats fed a high-fat high-sucrose diet. Obesity 2:976–979

    Article  Google Scholar 

  37. Turnbaugh PJ, Ley RE, Mahowald MS, Magrini V, Mardis ER, Gordon JI (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444:1027–1131

    Article  Google Scholar 

  38. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP et al (2009) A core gut microbiome in obese and lean twins. Nature 457:480–484

    Article  CAS  Google Scholar 

  39. Schwiertz A, Taras D, Schafer K, Beijer S, Bos NA, Donus C (2010) Microbiota and SCFA in lean and overweight healthy subjects. Obesity 18:190–195

    Article  Google Scholar 

  40. Selma MV, Espín CJ, Tomás-Barberán FA (2009) Interaction between phenoliccs and gut microbiota: role in human health. J Agric Food Chem 57:6485–6501

    Article  CAS  Google Scholar 

  41. Dueñas M, Cueva C, Muñoz-González I, Jiménez-Girón A, Sánchez-Patán F, Santos-Buelga C, Moreno-Arribas C, Bartolomé B (2015) Studies on modulation of gut microbiota by wine polyphenols: from isolated cultures to omic approaches. Antioxidants 4:1–21

    Article  Google Scholar 

  42. Yamakoshi J, Tokutake S, Kikuchi M, Kubota Y, Konishi Y, Mitsuoka T (2001) Effect of proanthocyanidin-rich extract from grape seeds on human fecal flora and fecal odor. Microbiol Ecol Health Dis 13:25–31

    Article  CAS  Google Scholar 

  43. De La Serre CB, Ellis CL, Lee J, Hartman AL, Rutledge JC, Raybould HE (2010) Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation. Am J Physiol Gastrointest Liver Physiol 299:440–448

    Article  Google Scholar 

  44. Brinkworth GD, Noakes M, Clifton PM, Bird AR (2009) Comparative effects of very low-carbohydrate, high-fat and high-carbohydrate, low-fat weight-loss diets on bowel habit and faecal short-chain fatty acids and bacterial populations. Br J Nutr 101:1493–1502

    Article  CAS  Google Scholar 

  45. Weltman MD, Farrell GC, Hall P, Ingelman-Sundberg M, Liddle C (1998) Hepatic cytochrome p450 2E1 is increased in patients with nonalcoholic steatohepatitis. Hepatology 27:128–133

    Article  CAS  Google Scholar 

  46. Osabe M, Sugatani J, Fukuyama T, Ikushiro S, Ikari A, Miwa M (2008) Expression of hepatic UDP-glucuronosyltransferase 1A1 and 1A6 correlated with increased expression of the nuclear constitutive androstane receptor and peroxisome proliferator-activated receptor alpha in male rats fed a high-fat and high-sucrose diet. Drug Metab Dispos 36:294–302

    Article  CAS  Google Scholar 

  47. Reagan-Shaw S, Nihal M, Ahmad N (2008) Dose translation from animal to human studies revisited. Faseb J 22:259–261

    Article  Google Scholar 

  48. Knaze V, Zamora-Ros R, Luján-Barroso L, Romieu I, Scalbert A, Slimani N, Riboli E, Van Rossum CTM, Bueno-de-Mesquita HB, Trichopulou A et al (2012) Intake estimation of total and individual flavan-3-ols, proanthocyanidins and theaflavins, their food sources and determinants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Br J Nutr 28:1095–1108

    Article  Google Scholar 

  49. Yamakoshi J, Saito M, Kataoka S, Kikuchi M (2012) Safety evaluation of proanthocyanidin-rich extract from grape seeds. Food Chem Toxicol 40:599–607

    Article  Google Scholar 

Download references

Acknowledgments

Language revision by Christopher Evans is appreciated. This research was supported by the Spanish Ministry of Science and Innovation (Grants: AGL2009-12374-C03-01, -02 and -03; and AGL2013-49079-C2-1, 2 and -R, and through a doctoral fellowship to L.M.). The Panamanian Government (SENACYT/IFARHU) awarded a graduate fellowship to E.M.-T. The ISCIII is acknowledged for a “Sara Borrell” postdoctoral contract to J.P.-J. (CD09/00068). The funding sources did not have any role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jara Pérez-Jiménez.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 131 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Molinar-Toribio, E., Fuguet, E., Ramos-Romero, S. et al. A high-fat high-sucrose diet affects the long-term metabolic fate of grape proanthocyanidins in rats. Eur J Nutr 57, 339–349 (2018). https://doi.org/10.1007/s00394-016-1323-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-016-1323-9

Keywords

Navigation