Pomegranate and green tea extracts protect against ER stress induced by a high-fat diet in skeletal muscle of mice

Abstract

Purpose

We tested the hypothesis that polyphenol-rich extracts can reduce endoplasmic reticulum (ER) stress induced by a high-fat diet (HFD) in skeletal muscle of mice.

Methods

Mice were randomly assigned to four groups receiving during 20 weeks either a standard chow control (CTRL), or a HFD supplemented, or not, with pomegranate (HFD + P) or green tea (HFD + GT) extracts. After the nutritional intervention, mice were killed and gastrocnemius muscles were taken. Proteins and mRNA were measured by Western blot and RT-qPCR, respectively.

Results

Body weight gain and visceral fat were higher in HFD, HFD + P and HFD + GT than in CTRL. The markers of the unfolded protein response BiP, XBP1u, XBP1s and ATF4 were higher only in HFD. In HFD + P and HFD + GT, this increase was not observed except for CHOP, which was elevated in all HFD groups. HFD increased also markers of ubiquitin–proteasome pathway, autophagy and oxidative stress, which were kept low in HFD + P and HFD + GT groups.

Conclusion

Our data provide evidence for a protective effect of pomegranate and green tea extracts against ER stress, oxidative stress and protein degradation induced by HFD in skeletal muscle. They give arguments for a usefulness of these natural nutritional compounds to fight against cellular dysfunctions related to fat excess.

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Abbreviations

ER:

Endoplasmic reticulum

UPR:

Unfolded protein response

HFD:

High-fat diet

EGCG:

Epigallocatechin gallate

P:

Pomegranate

GT:

Green tea

References

  1. 1.

    Eckardt K, Taube A, Eckel J (2011) Obesity-associated insulin resistance in skeletal muscle: role of lipid accumulation and physical inactivity. Rev Endocr Metab Disord 12:163–172

    Article  CAS  Google Scholar 

  2. 2.

    Samuel VT, Petersen KF, Shulman GI (2010) Lipid-induced insulin resistance: unravelling the mechanism. Lancet 375:2267–2277

    Article  CAS  Google Scholar 

  3. 3.

    Franklin RM, Kanaley JA (2009) Intramyocellular lipids: effect of age, obesity, and exercise. Phys Sportsmed 37:20–26

    Article  Google Scholar 

  4. 4.

    Tsiotra PC, Tsigos C (2006) Stress, the endoplasmic reticulum, and insulin resistance. Ann N Y Acad Sci 1083:63–76

    Article  CAS  Google Scholar 

  5. 5.

    Deldicque L, Cani PD, Philp A, Raymackers JM, Meakin PJ et al (2010) The unfolded protein response is activated in skeletal muscle by high-fat feeding: potential role in the downregulation of protein synthesis. Am J Physiol Endocrinol Metab 299:E695–E705

    Article  CAS  Google Scholar 

  6. 6.

    Deldicque L, Cani PD, Delzenne NM, Baar K, Francaux M (2013) Endurance training in mice increases the unfolded protein response induced by a high-fat diet. J Physiol Biochem 69:215–225

    Article  CAS  Google Scholar 

  7. 7.

    Pierre N, Deldicque L, Barbe C, Naslain D, Cani PD et al (2013) Toll-like receptor 4 knockout mice are protected against endoplasmic reticulum stress induced by a high-fat diet. PLoS ONE 8:e65061

    Article  CAS  Google Scholar 

  8. 8.

    Zhang K, Kaufman RJ (2008) From endoplasmic-reticulum stress to the inflammatory response. Nature 454:455–462

    Article  CAS  Google Scholar 

  9. 9.

    Gandeboeuf D, Dupre C, Roeckel-Drevet P, Nicolas P, Chevalier G (1997) Typing Tuber ectomycorrhizae by polymerase chain amplification of the internal transcribed spacer of rDNA and the sequence characterized amplified region markers. Can J Microbiol 43:723–728

    Article  CAS  Google Scholar 

  10. 10.

    Viladomiu M, Hontecillas R, Lu P, Bassaganya-Riera J (2013) Preventive and prophylactic mechanisms of action of pomegranate bioactive constituents. Evid Based Complement Alternat Med 2013:789764

    Article  Google Scholar 

  11. 11.

    Rosen T (2012) Green tea catechins: biologic properties, proposed mechanisms of action, and clinical implications. J Drugs Dermatol 11:e55–e60

    Google Scholar 

  12. 12.

    Al-Muammar MN, Khan F (2012) Obesity: the preventive role of the pomegranate (Punica granatum). Nutrition 28:595–604

    Article  CAS  Google Scholar 

  13. 13.

    Ismail T, Sestili P, Akhtar S (2012) Pomegranate peel and fruit extracts: a review of potential anti-inflammatory and anti-infective effects. J Ethnopharmacol 143:397–405

    Article  CAS  Google Scholar 

  14. 14.

    Wolfram S (2007) Effects of green tea and EGCG on cardiovascular and metabolic health. J Am Coll Nutr 26:373S–388S

    Article  CAS  Google Scholar 

  15. 15.

    Singh BN, Shankar S, Srivastava RK (2011) Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. Biochem Pharmacol 82:1807–1821

    Article  CAS  Google Scholar 

  16. 16.

    Malhotra S, Suri S, Tuli R (2009) Antioxidant activity of citrus cultivars and chemical composition of Citrus karna essential oil. Planta Med 75:62–64

    Article  CAS  Google Scholar 

  17. 17.

    Lee YJ, Kim SJ, Heo TH (2011) Protective effect of catechin in type I Gaucher disease cells by reducing endoplasmic reticulum stress. Biochem Biophys Res Commun 413:254–258

    Article  CAS  Google Scholar 

  18. 18.

    Revesz K, Tutto A, Konta L (2007) Effect of green tea flavonols on the function of the endoplasmic reticulum. Orv Hetil 148:1903–1907

    Article  Google Scholar 

  19. 19.

    Flamment M, Hajduch E, Ferre P, Foufelle F (2012) New insights into ER stress-induced insulin resistance. Trends Endocrinol Metab 23:381–390

    Article  CAS  Google Scholar 

  20. 20.

    Sandri M, Sandri C, Gilbert A, Skurk C, Calabria E et al (2004) Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell 117:399–412

    Article  CAS  Google Scholar 

  21. 21.

    Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L et al (2001) Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 294:1704–1708

    Article  CAS  Google Scholar 

  22. 22.

    Malhotra JD, Kaufman RJ (2007) Endoplasmic reticulum stress and oxidative stress: a vicious cycle or a double-edged sword? Antioxid Redox Signal 9:2277–2293

    Article  CAS  Google Scholar 

  23. 23.

    Malhotra JD, Miao H, Zhang K, Wolfson A, Pennathur S et al (2008) Antioxidants reduce endoplasmic reticulum stress and improve protein secretion. Proc Natl Acad Sci USA 105:18525–18530

    Article  CAS  Google Scholar 

  24. 24.

    Xue X, Piao JH, Nakajima A, Sakon-Komazawa S, Kojima Y et al (2005) Tumor necrosis factor alpha (TNFalpha) induces the unfolded protein response (UPR) in a reactive oxygen species (ROS)-dependent fashion, and the UPR counteracts ROS accumulation by TNFalpha. J Biol Chem 280:33917–33925

    Article  CAS  Google Scholar 

  25. 25.

    Nunez-Sanchez MA, Garcia-Villalba R, Monedero-Saiz T, Garcia-Talavera NV, Gomez-Sanchez MB et al (2014) Targeted metabolic profiling of pomegranate polyphenols and urolithins in plasma, urine and colon tissues from colorectal cancer patients. Mol Nutr Food Res. doi:10.1002/mnfr.201300931

  26. 26.

    Hamoud S, Hayek T, Volkova N, Attias J, Moscoviz D et al (2014) Pomegranate extract (POMx) decreases the atherogenicity of serum and of human monocyte-derived macrophages (HMDM) in simvastatin-treated hypercholesterolemic patients: a double-blinded, placebo-controlled, randomized, prospective pilot study. Atherosclerosis 232:204–210

    Article  CAS  Google Scholar 

  27. 27.

    Hanley MJ, Masse G, Harmatz JS, Court MH, Greenblatt DJ (2012) Pomegranate juice and pomegranate extract do not impair oral clearance of flurbiprofen in human volunteers: divergence from in vitro results. Clin Pharmacol Ther 92:651–657

    Article  CAS  Google Scholar 

  28. 28.

    Liu K, Zhou R, Wang B, Chen K, Shi LY et al (2013) Effect of green tea on glucose control and insulin sensitivity: a meta-analysis of 17 randomized controlled trials. Am J Clin Nutr 98:340–348

    Article  CAS  Google Scholar 

  29. 29.

    Walkowiak J, Bajerska J, Kargulewicz A, Lisowska A, Siedlerski G et al (2013) Single dose of green tea extract decreases lipid digestion and absorption from a test meal in humans. Acta Biochim Pol 60:481–483

    CAS  Google Scholar 

  30. 30.

    Manach C, Scalbert A, Morand C, Remesy C, Jimenez L (2004) Polyphenols: food sources and bioavailability. Am J Clin Nutr 79:727–747

    CAS  Google Scholar 

  31. 31.

    Terpstra AH (2001) Differences between humans and mice in efficacy of the body fat lowering effect of conjugated linoleic acid: role of metabolic rate. J Nutr 131:2067–2068

    CAS  Google Scholar 

  32. 32.

    Lei F, Zhang XN, Wang W, Xing DM, Xie WD et al (2007) Evidence of anti-obesity effects of the pomegranate leaf extract in high-fat diet induced obese mice. Int J Obes (Lond) 31:1023–1029

    Article  CAS  Google Scholar 

  33. 33.

    Vroegrijk IO, van Diepen JA, van den Berg S, Westbroek I, Keizer H et al (2011) Pomegranate seed oil, a rich source of punicic acid, prevents diet-induced obesity and insulin resistance in mice. Food Chem Toxicol 49:1426–1430

    Article  CAS  Google Scholar 

  34. 34.

    Neyrinck AM, Van Hee VF, Bindels LB, De Backer F, Cani PD et al (2013) Polyphenol-rich extract of pomegranate peel alleviates tissue inflammation and hypercholesterolaemia in high-fat diet-induced obese mice: potential implication of the gut microbiota. Br J Nutr 109:802–809

    Article  CAS  Google Scholar 

  35. 35.

    Cunha CA, Lira FS, Rosa Neto JC, Pimentel GD, Souza GI et al (2013) Green tea extract supplementation induces the lipolytic pathway, attenuates obesity, and reduces low-grade inflammation in mice fed a high-fat diet. Mediators Inflamm 2013:635470

    Article  Google Scholar 

  36. 36.

    Shimotoyodome A, Haramizu S, Inaba M, Murase T, Tokimitsu I (2005) Exercise and green tea extract stimulate fat oxidation and prevent obesity in mice. Med Sci Sports Exerc 37:1884–1892

    Article  Google Scholar 

  37. 37.

    Kao YH, Chang HH, Lee MJ, Chen CL (2006) Tea, obesity, and diabetes. Mol Nutr Food Res 50:188–210

    Article  CAS  Google Scholar 

  38. 38.

    Lee AS (2001) The glucose-regulated proteins: stress induction and clinical applications. Trends Biochem Sci 26:504–510

    Article  CAS  Google Scholar 

  39. 39.

    Yoshida H, Matsui T, Yamamoto A, Okada T, Mori K (2001) XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 107:881–891

    Article  CAS  Google Scholar 

  40. 40.

    Cullinan SB, Diehl JA (2006) Coordination of ER and oxidative stress signaling: the PERK/Nrf2 signaling pathway. Int J Biochem Cell Biol 38:317–332

    Article  CAS  Google Scholar 

  41. 41.

    Wek RC, Jiang HY, Anthony TG (2006) Coping with stress: eIF2 kinases and translational control. Biochem Soc Trans 34:7–11

    Article  CAS  Google Scholar 

  42. 42.

    Miyamoto N, Izumi H, Miyamoto R, Bin H, Kondo H et al (2011) Transcriptional regulation of activating transcription factor 4 under oxidative stress in retinal pigment epithelial ARPE-19/HPV-16 cells. Invest Ophthalmol Vis Sci 52:1226–1234

    Article  CAS  Google Scholar 

  43. 43.

    Oyadomari S, Mori M (2004) Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ 11:381–389

    Article  CAS  Google Scholar 

  44. 44.

    Dey S, Baird TD, Zhou D, Palam LR, Spandau DF et al (2010) Both transcriptional regulation and translational control of ATF4 are central to the integrated stress response. J Biol Chem 285:33165–33174

    Article  CAS  Google Scholar 

  45. 45.

    Ding Y, Dai X, Jiang Y, Zhang Z, Bao L et al (2013) Grape seed proanthocyanidin extracts alleviate oxidative stress and ER stress in skeletal muscle of low-dose streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats. Mol Nutr Food Res 57:365–369

    Article  CAS  Google Scholar 

  46. 46.

    Deldicque L, Bertrand L, Patton A, Francaux M, Baar K (2011) ER stress induces anabolic resistance in muscle cells through PKB-induced blockade of mTORC1. PLoS ONE 6:e20993

    Article  CAS  Google Scholar 

  47. 47.

    Turner N, Kowalski GM, Leslie SJ, Risis S, Yang C et al (2013) Distinct patterns of tissue-specific lipid accumulation during the induction of insulin resistance in mice by high-fat feeding. Diabetologia 56:1638–1648

    Article  CAS  Google Scholar 

  48. 48.

    Chen N, Bezzina R, Hinch E, Lewandowski PA, Cameron-Smith D et al (2009) Green tea, black tea, and epigallocatechin modify body composition, improve glucose tolerance, and differentially alter metabolic gene expression in rats fed a high-fat diet. Nutr Res 29:784–793

    Article  CAS  Google Scholar 

  49. 49.

    Park JH, Choi YJ, Kim YW, Kim SP, Cho HC et al (2013) Green tea extract with polyethylene glycol-3350 reduces body weight and improves glucose tolerance in db/db and high-fat diet mice. Naunyn Schmiedebergs Arch Pharmacol 386:733–745

    Article  CAS  Google Scholar 

  50. 50.

    Ding Y, Zhang Z, Dai X, Jiang Y, Bao L et al (2013) Grape seed proanthocyanidins ameliorate pancreatic beta-cell dysfunction and death in low-dose streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats partially by regulating endoplasmic reticulum stress. Nutr Metab (Lond) 10:51

    Article  CAS  Google Scholar 

  51. 51.

    Hotamisligil GS (2010) Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 140:900–917

    Article  CAS  Google Scholar 

  52. 52.

    Van Der Heide LP, Hoekman MF, Smidt MP (2004) The ins and outs of FoxO shuttling: mechanisms of FoxO translocation and transcriptional regulation. Biochem J 380:297–309

    Article  Google Scholar 

  53. 53.

    Yuzefovych LV, Musiyenko SI, Wilson GL, Rachek LI (2013) Mitochondrial DNA damage and dysfunction, and oxidative stress are associated with endoplasmic reticulum stress, protein degradation and apoptosis in high fat diet-induced insulin resistance mice. PLoS ONE 8:e54059

    Article  CAS  Google Scholar 

  54. 54.

    Wang H, Lai YJ, Chan YL, Li TL, Wu CJ (2011) Epigallocatechin-3-gallate effectively attenuates skeletal muscle atrophy caused by cancer cachexia. Cancer Lett 305:40–49

    Article  CAS  Google Scholar 

  55. 55.

    Zhao J, Brault JJ, Schild A, Goldberg AL (2008) Coordinate activation of autophagy and the proteasome pathway by FoxO transcription factor. Autophagy 4:378–380

    Article  CAS  Google Scholar 

  56. 56.

    Mammucari C, Milan G, Romanello V, Masiero E, Rudolf R et al (2007) FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab 6:458–471

    Article  CAS  Google Scholar 

  57. 57.

    Kaneto H, Matsuoka TA, Nakatani Y, Kawamori D, Miyatsuka T et al (2005) Oxidative stress, ER stress, and the JNK pathway in type 2 diabetes. J Mol Med (Berl) 83:429–439

    Article  CAS  Google Scholar 

  58. 58.

    Lee J, Giordano S, Zhang J (2012) Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling. Biochem J 441:523–540

    Article  CAS  Google Scholar 

  59. 59.

    Yiannakopoulou E (2013) Targeting oxidative stress response by green tea polyphenols: clinical implications. Free Radic Res 47:667–671

  60. 60.

    Cnop M, Foufelle F, Velloso LA (2012) Endoplasmic reticulum stress, obesity and diabetes. Trends Mol Med 18:59–68

    Article  CAS  Google Scholar 

  61. 61.

    Dutta K, Podolin DA, Davidson MB, Davidoff AJ (2001) Cardiomyocyte dysfunction in sucrose-fed rats is associated with insulin resistance. Diabetes 50:1186–1192

    Article  CAS  Google Scholar 

  62. 62.

    Omar B, Pacini G, Ahren B (2012) Differential development of glucose intolerance and pancreatic islet adaptation in multiple diet induced obesity models. Nutrients 4:1367–1381

    Article  CAS  Google Scholar 

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Acknowledgments

This work was supported by the “Chaire Delhaize” of the “Fondation Louvain” (Belgium). JR is a recipient of a postdoctoral fellowship financed by ELEONOR sprl. HG was a postdoctoral fellow supported by the “Chaire Delhaize”.

Conflict of interest

The authors have declared no conflict of interest.

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Correspondence to Marc Francaux.

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Rodriguez, J., Gilson, H., Jamart, C. et al. Pomegranate and green tea extracts protect against ER stress induced by a high-fat diet in skeletal muscle of mice. Eur J Nutr 54, 377–389 (2015). https://doi.org/10.1007/s00394-014-0717-9

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Keywords

  • High-fat diet
  • Unfolded protein response
  • Polyphenols
  • Protein degradation
  • Oxidative stress