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Pomegranate peel anthocyanins prevent diet-induced obesity and insulin resistance in association with modulation of the gut microbiota in mice

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Abstract

Purpose

Pomegranate peels are rich in anthocyanins. The present study aimed to explore the beneficial effects of pomegranate peel anthocyanins (PPA) on obesity and gut microbiota in mice with high-fat diet (HFD)-induced obesity.

Methods

Specific pathogen-free (SPF) male C57BL/6 J mice were randomly divided into three groups and fed with low-fat diet (LFD, 10% fat energy), HFD (45% fat energy), or HFD supplemented with PPA by intragastric administration for 15 weeks. Body weight and food intake were monitored weekly. The obesity-related biochemical indexes and hepatic gene expression levels were determined. The compositions of the gut microbiota were analyzed by 16S rRNA sequencing, and the association between the gut microbiota and obesity-related indicators was investigated by Spearman correlation analysis.

Results

The results showed that the body weight gain, steatosis scores and insulin resistance index in the PPA group decreased by 27.46%, 56.25%, and 46.07%, respectively, compared to the HFD group. Gene expression analysis indicated that PPA supplement improved the genes expression profiles involved in glucose and lipid metabolism compared with the mice fed HFD alone. Meanwhile, PPA significantly changed the composition of the gut microbiota, which were closely correlated with the obesity-related biomarkers.

Conclusion

This study suggested that PPA could be a beneficial treatment option for alleviating HFD-induced obesity and related metabolic disorders by targeting microbiota and lipid metabolism.

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References

  1. Despres JP, Lemieux I (2006) Abdominal obesity and metabolic syndrome. Nature 444(7121):881–887. https://doi.org/10.1038/nature05488

    Article  CAS  PubMed  Google Scholar 

  2. Authors N (2013) Obesity and food science being part of the solution. J Food Sci. https://doi.org/10.1111/1750-3841.12261

    Article  Google Scholar 

  3. Yun JW (2010) Possible anti-obesity therapeutics from nature—a review. Phytochemistry 71(14–15):1625–1641. https://doi.org/10.1016/j.phytochem.2010.07.011

    Article  CAS  PubMed  Google Scholar 

  4. Powell TM, Khera A (2010) Therapeutic approaches to obesity. Curr Treat Options Cardiovasc Med 12(4):381–395. https://doi.org/10.1007/s11936-010-0080-y

    Article  PubMed  Google Scholar 

  5. Wang Q, Jiao L, He C, Sun H, Cai Q, Han T, Hu H (2017) Alteration of gut microbiota in association with cholesterol gallstone formation in mice. BMC Gastroenterol 17(1):74. https://doi.org/10.1186/s12876-017-0629-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Canfora EE, Meex RCR, Venema K, Blaak EE (2019) Gut microbial metabolites in obesity, NAFLD and T2DM. Nat Rev Endocrinol 15(5):261–273. https://doi.org/10.1038/s41574-019-0156-z

    Article  CAS  PubMed  Google Scholar 

  7. Qiu X, Macchietto MG, Liu X, Lu Y, Ma Y, Guo H, Saqui-Salces M, Bernlohr DA, Chen C, Shen S, Chen X (2021) Identification of gut microbiota and microbial metabolites regulated by an antimicrobial peptide lipocalin 2 in high fat diet-induced obesity. Int J Obesity 45(1):143–154. https://doi.org/10.1038/s41366-020-00712-2

    Article  CAS  Google Scholar 

  8. Crovesy L, Masterson D, Rosado EL (2020) Profile of the gut microbiota of adults with obesity: a systematic review. Eur J Clin Nutr 74(9):1251–1262. https://doi.org/10.1038/s41430-020-0607-6

    Article  PubMed  Google Scholar 

  9. Delzenne NM, Rodriguez J, Olivares M, Neyrinck AM (2020) Microbiome response to diet: focus on obesity and related diseases. Rev Endocr Metab Dis 21(3):369–380. https://doi.org/10.1007/s11154-020-09572-7

    Article  Google Scholar 

  10. Hou D, Zhao Q, Yousaf L, Xue Y, Shen Q (2021) Beneficial effects of mung bean seed coat on the prevention of high-fat diet-induced obesity and the modulation of gut microbiota in mice. Eur J Nutr 60(4):2029–2045. https://doi.org/10.1007/s00394-020-02395-x

    Article  CAS  PubMed  Google Scholar 

  11. Chen J, He X, Huang J (2014) Diet effects in gut microbiome and obesity. J Food Sci 79(4):R442-451. https://doi.org/10.1111/1750-3841.12397

    Article  CAS  PubMed  Google Scholar 

  12. Sonnenburg JL, Bäckhed F (2016) Diet–microbiota interactions as moderators of human metabolism. Nature 535(7610):56–64. https://doi.org/10.1038/nature18846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Portune KJ, Benítez-Páez A, Del Pulgar EMG, Cerrudo V, Sanz Y (2017) Gut microbiota, diet, and obesity-related disorders—the good, the bad, and the future challenges. Mol Nutri Food Res 61(1):1600252. https://doi.org/10.1002/mnfr.201600252

    Article  CAS  Google Scholar 

  14. Fu C, Jiang Y, Guo J, Su Z (2016) Natural products with anti-obesity effects and different mechanisms of action. J Agric Food Chem 64(51):9571–9585. https://doi.org/10.1021/acs.jafc.6b04468

    Article  CAS  PubMed  Google Scholar 

  15. Salehi B, Sharifi-Rad J, Cappellini F, Reiner Z, Zorzan D, Imran M, Sener B, Kilic M, El-Shazly M, Fahmy NM, Al-Sayed E, Martorell M, Tonelli C, Petroni K, Docea AO, Calina D, Maroyi A (2020) The therapeutic potential of anthocyanins: current approaches based on their molecular mechanism of action. Front Pharmacol 11:1300. https://doi.org/10.3389/fphar.2020.01300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Johanningsmeier SD, Harris GK (2011) Pomegranate as a functional food and nutraceutical source. Annu Rev Food Sci Technol 2(1):181–201. https://doi.org/10.1146/annurev-food-030810-153709

    Article  CAS  PubMed  Google Scholar 

  17. Magangana TP, Makunga NP, Fawole OA, Opara UL (2020) Processing factors affecting the phytochemical and nutritional properties of pomegranate (Punica granatum L.) peel waste: a review. Molecules 25(20):4690

    Article  CAS  Google Scholar 

  18. Huang TH-W, Peng G, Kota BP, Li GQ, Yamahara J, Roufogalis BD, Li Y (2005) Pomegranate flower improves cardiac lipid metabolism in a diabetic rat model: role of lowering circulating lipids. Br J Pharmacol 145(6):767–774. https://doi.org/10.1038/sj.bjp.0706245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lei F, Zhang XN, Wang W, Xing DM, Xie WD, Su H, Du LJ (2007) Evidence of anti-obesity effects of the pomegranate leaf extract in high-fat diet induced obese mice. Int J Obes 31(6):1023–1029. https://doi.org/10.1038/sj.ijo.0803502

    Article  CAS  Google Scholar 

  20. Raffaele M, Licari M, Amin S, Alex R, Shen H-h, Singh SP, Vanella L, Rezzani R, Bonomini F, Peterson SJ, Stec DE, Abraham NG (2020) Cold press pomegranate seed oil attenuates dietary-obesity induced hepatic steatosis and fibrosis through antioxidant and mitochondrial pathways in obese mice. Int J Mol Sci 21(15):5469

    Article  CAS  Google Scholar 

  21. Zhao R, Long X, Yang J, Du L, Zhang X, Li J, Hou C (2019) Pomegranate peel polyphenols reduce chronic low-grade inflammatory responses by modulating gut microbiota and decreasing colonic tissue damage in rats fed a high-fat diet. Food Funct 10(12):8273–8285. https://doi.org/10.1039/C9FO02077B

    Article  CAS  PubMed  Google Scholar 

  22. Song H, Chu Q, Xu D, Xu Y, Zheng X (2016) Purified betacyanins from hylocereus undatus peel ameliorate obesity and insulin resistance in high-fat-diet-fed mice. J Agric Food Chem 64(1):236–244. https://doi.org/10.1021/acs.jafc.5b05177

    Article  CAS  PubMed  Google Scholar 

  23. Folch J, Lees M, Stanley GHS (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226(1):497–509. https://doi.org/10.1016/S0021-9258(18)64849-5

    Article  CAS  PubMed  Google Scholar 

  24. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(–Delta Delta C(T)) method. Methods 25(4):402–408. https://doi.org/10.1006/meth.2001.1262

    Article  CAS  PubMed  Google Scholar 

  25. Basu A, Penugonda K (2009) Pomegranate juice: a heart-healthy fruit juice. Nutr Rev 67(1):49–56. https://doi.org/10.1111/j.1753-4887.2008.00133.x

    Article  PubMed  Google Scholar 

  26. Panichayupakaranant P, Tewtrakul S, Yuenyongsawad S (2010) Antibacterial, anti-inflammatory and anti-allergic activities of standardised pomegranate rind extract. Food Chem 123:400–403. https://doi.org/10.1016/j.foodchem.2010.04.054

    Article  CAS  Google Scholar 

  27. Fischer UA, Carle R, Kammerer DR (2011) Identification and quantification of phenolic compounds from pomegranate (Punica granatum L.) peel, mesocarp, aril and differently produced juices by HPLC-DAD–ESI/MSn. Food Chem 127(2):807–821. https://doi.org/10.1016/j.foodchem.2010.12.156

    Article  CAS  PubMed  Google Scholar 

  28. El-Sayyad HIH (2015) Cholesterol overload impairing cerebellar function: the promise of natural products. Nutrition 31(5):621–630. https://doi.org/10.1016/j.nut.2014.10.017

    Article  CAS  PubMed  Google Scholar 

  29. Spilmont M, Léotoing L, Davicco M-J, Lebecque P, Mercier S, Miot-Noirault E, Pilet P, Rios L, Wittrant Y, Coxam V (2014) Pomegranate and its derivatives can improve bone health through decreased inflammation and oxidative stress in an animal model of postmenopausal osteoporosis. Eur J Nutr 53(5):1155–1164. https://doi.org/10.1007/s00394-013-0615-6

    Article  CAS  PubMed  Google Scholar 

  30. Esmaillzadeh A, Tahbaz F, Gaieni I, Alavi-Majd H, Azadbakht L (2004) Concentrated pomegranate juice improves lipid profiles in diabetic patients with hyperlipidemia. J Med Food 7(3):305–308. https://doi.org/10.1089/jmf.2004.7.305

    Article  CAS  PubMed  Google Scholar 

  31. Esmaillzadeh A, Tahbaz F, Gaieni I, Alavi-Majd H, Azadbakht L (2006) Cholesterol-lowering effect of concentrated pomegranate juice consumption in type II diabetic patients with hyperlipidemia. Int J Vitam Nutr Res 76(3):147–151. https://doi.org/10.1024/0300-9831.76.3.147

    Article  CAS  PubMed  Google Scholar 

  32. Xi Y, Li H (2020) Role of farnesoid X receptor in hepatic steatosis in nonalcoholic fatty liver disease. Biomed Pharmacother 121:109609. https://doi.org/10.1016/j.biopha.2019.109609

    Article  CAS  PubMed  Google Scholar 

  33. Longato L, Tong M, Wands JR, de la Monte SM (2012) High fat diet induced hepatic steatosis and insulin resistance: role of dysregulated ceramide metabolism. Hepatol Res 42(4):412–427. https://doi.org/10.1111/j.1872-034X.2011.00934.x

    Article  CAS  PubMed  Google Scholar 

  34. Garcia-Serrano AM, Duarte JMN (2020) Brain metabolism alterations in type 2 diabetes: what did we learn from diet-induced diabetes models? Front Neurosci. https://doi.org/10.3389/fnins.2020.00229

    Article  PubMed  PubMed Central  Google Scholar 

  35. Harzallah A, Hammami M, Kępczyńska MA, Hislop DC, Arch JRS, Cawthorne MA, Zaibi MS (2016) Comparison of potential preventive effects of pomegranate flower, peel and seed oil on insulin resistance and inflammation in high-fat and high-sucrose diet-induced obesity mice model. Arch Physiol Biochem 122(2):75–87. https://doi.org/10.3109/13813455.2016.1148053

    Article  CAS  PubMed  Google Scholar 

  36. Esmaeilinezhad Z, Babajafari S, Sohrabi Z, Eskandari MH, Amooee S, Barati-Boldaji R (2019) Effect of synbiotic pomegranate juice on glycemic, sex hormone profile and anthropometric indices in PCOS: a randomized, triple blind, controlled trial. Nutr Metab Cardiovasc Dis 29(2):201–208. https://doi.org/10.1016/j.numecd.2018.07.002

    Article  CAS  PubMed  Google Scholar 

  37. Huang H, Liao D, Chen G, Chen H, Zhu Y (2017) Lack of efficacy of pomegranate supplementation for glucose management, insulin levels and sensitivity: evidence from a systematic review and meta-analysis. Nutr J 16(1):67. https://doi.org/10.1186/s12937-017-0290-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Ilyas Z, Perna S, Al-Thawadi S, Alalwan TA, Riva A, Petrangolini G, Gasparri C, Infantino V, Peroni G, Rondanelli M (2020) The effect of Berberine on weight loss in order to prevent obesity: a systematic review. Biomed Pharmacother 127:110137. https://doi.org/10.1016/j.biopha.2020.110137

    Article  CAS  PubMed  Google Scholar 

  39. Gautier-Stein A, Soty M, Chilloux J, Zitoun C, Rajas F, Mithieux G (2012) Glucotoxicity induces glucose-6-phosphatase catalytic unit expression by acting on the interaction of HIF-1α with CREB-binding protein. Diabetes 61(10):2451. https://doi.org/10.2337/db11-0986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Krause C, Geißler C, Tackenberg H, El Gammal AT, Wolter S, Spranger J, Mann O, Lehnert H, Kirchner H (2020) Multi-layered epigenetic regulation of IRS2 expression in the liver of obese individuals with type 2 diabetes. Diabetologia 63(10):2182–2193. https://doi.org/10.1007/s00125-020-05212-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Illiano P, Brambilla R, Parolini C (2020) The mutual interplay of gut microbiota, diet and human disease. FEBS J 287(5):833–855. https://doi.org/10.1111/febs.15217

    Article  CAS  PubMed  Google Scholar 

  42. Fang J (2014) Bioavailability of anthocyanins. Drug Metab Rev 46(4):508–520. https://doi.org/10.3109/03602532.2014.978080

    Article  CAS  PubMed  Google Scholar 

  43. Hidalgo M, Oruna-Concha MJ, Kolida S, Walton GE, Kallithraka S, Spencer JPE, Gibson GR, de Pascual-Teresa S (2012) Metabolism of anthocyanins by human gut microflora and their influence on gut bacterial growth. J Agr Food Chem 60(15):3882–3890. https://doi.org/10.1021/jf3002153

    Article  CAS  Google Scholar 

  44. Singer-Englar T, Barlow G, Mathur R (2019) Obesity, diabetes, and the gut microbiome: an updated review. Expert Rev Gastroenterol Hepatol 13(1):3–15. https://doi.org/10.1080/17474124.2019.1543023

    Article  CAS  PubMed  Google Scholar 

  45. Shin NR, Whon TW, Bae JW (2015) Proteobacteria: microbial signature of dysbiosis in gut microbiota. Trends Biotechnol 33(9):496–503. https://doi.org/10.1016/j.tibtech.2015.06.011

    Article  CAS  PubMed  Google Scholar 

  46. Zhou K (2017) Strategies to promote abundance of Akkermansia muciniphila, an emerging probiotics in the gut, evidence from dietary intervention studies. J Funct Foods 33:194–201. https://doi.org/10.1016/j.jff.2017.03.045

    Article  PubMed  PubMed Central  Google Scholar 

  47. Li Z, Henning SM, Lee RP, Lu QY, Summanen PH, Thames G, Corbett K, Downes J, Tseng CH, Finegold SM, Heber D (2015) Pomegranate extract induces ellagitannin metabolite formation and changes stool microbiota in healthy volunteers. Food Funct 6(8):2487–2495. https://doi.org/10.1039/c5fo00669d

    Article  CAS  PubMed  Google Scholar 

  48. Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, Liang S, Zhang W, Guan Y, Shen D, Peng Y, Zhang D, Jie Z, Wu W, Qin Y, Xue W, Li J, Han L, Lu D, Wu P, Dai Y, Sun X, Li Z, Tang A, Zhong S, Li X, Chen W, Xu R, Wang M, Feng Q, Gong M, Yu J, Zhang Y, Zhang M, Hansen T, Sanchez G, Raes J, Falony G, Okuda S, Almeida M, LeChatelier E, Renault P, Pons N, Batto JM, Zhang Z, Chen H, Yang R, Zheng W, Li S, Yang H, Wang J, Ehrlich SD, Nielsen R, Pedersen O, Kristiansen K, Wang J (2012) A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490(7418):55–60. https://doi.org/10.1038/nature11450

    Article  CAS  PubMed  Google Scholar 

  49. Louis S, Tappu RM, Damms-Machado A, Huson DH, Bischoff SC (2016) Characterization of the gut microbial community of obese patients following a weight-loss intervention using whole metagenome shotgun sequencing. PLoS One 11(2):e0149564. https://doi.org/10.1371/journal.pone.0149564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Zeng Q, Li D, He Y, Li Y, Yang Z, Zhao X, Liu Y, Wang Y, Sun J, Feng X, Wang F, Chen J, Zheng Y, Yang Y, Sun X, Xu X, Wang D, Kenney T, Jiang Y, Gu H, Li Y, Zhou K, Li S, Dai W (2019) Discrepant gut microbiota markers for the classification of obesity-related metabolic abnormalities. Sci Rep 9(1):13424. https://doi.org/10.1038/s41598-019-49462-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Oddi S, Huber P, Rocha Faria Duque AL, Vinderola G, Sivieri K (2020) Breast-milk derived potential probiotics as strategy for the management of childhood obesity. Food Res Int 137:109673. https://doi.org/10.1016/j.foodres.2020.109673

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (32072221, 31701031) and China Postdoctoral Science Foundation (2016M601006).

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Authors and Affiliations

  1. College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing, 210023, China

    Haizhao Song, Xinchun Shen & Rou Deng

  2. College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, China

    Qiang Chu & Xiaodong Zheng

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  1. Haizhao Song
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  2. Xinchun Shen
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  3. Rou Deng
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  4. Qiang Chu
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  5. Xiaodong Zheng
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Contributions

HS: designed the research, analyzed the data, and wrote the paper; XS: analyzed the data and wrote the paper; RD, QC: conducted the experiments and collected the data; XZ: provided essential materials and reviewed the manuscript; and all authors: read and approved the final manuscript.

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Correspondence to Haizhao Song or Xiaodong Zheng.

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Song, H., Shen, X., Deng, R. et al. Pomegranate peel anthocyanins prevent diet-induced obesity and insulin resistance in association with modulation of the gut microbiota in mice. Eur J Nutr 61, 1837–1847 (2022). https://doi.org/10.1007/s00394-021-02771-1

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