ABSTRACT:The aim of this study was to determine the potential of phenolic compounds from a fermented blackberry-blueberry beverage to reduce diet-induced obesity and hyperglycemia in mice fed a 60% high fat diet (HFD) for ten weeks after one week of pre-treatment. C57BL/6j mice were randomized into six groups and allowed to drink (ad libitum) an alcohol-free blackberry-blueberry beverage (AFFB, 8.4 mg ANC/kg BW/d), three doses of a phenolic extract (PAE) from AFFB at 0.1X, 1X and 2X anthocyanin (ANC) concentrations, sitagliptin (hypoglycemic positive control), or water (negative control). Weight and fat mass gain were attenuated in mice receiving the highest doses of PAE (18.9 mg ANC/kg BW/d, p < 0.05). There were also reductions (p < 0.05) in percent fat mass, epididymal fat pad weights, mean adipocyte diameters, and plasma triglycerides and cholesterol associated with PAE treatments. By the end of the study, fasting blood glucose for mice receiving 9 (1X) or 18.9 (2X) mg ANC/kg BW/d was significantly lower than in the water and the sitagliptin groups (p < 0.05). Histological and histochemical analysis revealed an unexpected change in liver of mice fed ANC at 1X or 2X doses consisting of liver enlargement and increased lipid deposition. PAE also induced the most differential gene expression changes, including highly significant downstream effects at all doses to reduce D-glucose concentrations. Overall, phenolic compounds from the fermented blueberryblackberry beverage had an impact to attenuate the development of obesity and fasting blood glucose in C57BL/6j mice.

KEY WORDS: Anthocyanin, phenolic, berries, diet-induced obesity, hyperglycemia, C57Bl/6j mice

链接全文

参考文献:

1. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2014. Atlanta, GA: U.S. DHHS, Centers for Disease Control and Prevention, 2014.
2. Burton-Freeman B. Postprandial metabolic events and fruit-derived phenolics: a review of the science. British J Nutr 2010; 104:S1-S14.
3. Ley SH, Hamdy O, Mohan V, Hu FB. Prevention and management of type 2 diabetes: dietary components and nutritional strategies. Lancet 2014; 383(9933):1999-2007.
4. Wedick NM, Pan A, Cassidy A, Rimm EB, Sampson L, Bernard R, Willet W, Hu FB, Sun Q, Dam RM. Dietary flavonoid intakes and risk of type 2 diabetes in US men and women. Am J Clin Nutr 2012; 95: 925-933.
5. Muraki I, Imamura F, Manson JE, Hu FB, Willett WC, van Dam RM. Fruit consumption and risk of type 2 diabetes: results from three prospective longitudinal cohort studies. BMJ 2013; 347:f5001.
6. Jennings A, Welch AA, Spector T, Macgregor A, Cassidy A. Intakes of anthocyanins and flavones are associated with biomarkers of insulin resistance and inflammation in women. J Nutr 2014; 144(2):202-208.
7. van Dam RM, Naidoo N, Landberg R. Dietary flavonoids and the development of type 2 diabetes and cardiovascular diseases: review of recent findings. Curr Opin Lipidol 2013;24(1):25-33.

8. Wu X, Beecher GR, Holden JM, Haytowitz DB, Gebhardt SE, Prior RL. Concentrations of anthocyanins in common foods in the United States and estimates of normal consumption. J Agric Food Chem 2006; 54:4069-4075.
9. Ferreira D, Slade D, Marais JPJ. Flavans and Proanthocyanidins. In: Flavonoids: Chemistry, Biochemistry, and Applications. (2006) Anderson OM and Markham KR. Taylor & Francis Group, Boca Raton, FL.
10. Stull A, Cash K, Johnson W, Champagne C, Cefalu W. Bioactives in blueberries improve insulin sensitivity in obese, insulin-resistant men and women. J Nutr 2010; 140:1764-1768.
11. Lyall KA, Hurst SM, Cooney J. Short-term blackcurrant extract consumption modulates exercise-induced oxidative stress and lipopolysaccharide-stimulated inflammatory responses. Am J Physiol Regul Integr Comp Physiol 2009; 297 (1): R70-81.
12. Giongo L, Bozza E, Caciagli P. Short-term blueberry intake enhances biological antioxidant potential and modulates inflammation markers in overweight and obese children. J Berry Res 2011; 1 (3):147-158.
13. Surwitt RS, Kuhn CM, Cochrane C, McCubbin JA, Feinglos MN. Diet-induced type II diabetes in C57BL/6J mice. Diabetes 1988; 37(9):1163-1167.
14. Winzell MS, Ahren B. The high-fat diet-fed mouse: a model for studying mechanisms andm treatment of impaired glucose tolerance and type 2 diabetes. Diabetes 2004; 53:S215-S219.
15. Prior RL, E Wilkes S, R Rogers T, Khanal RC, Wu X, Howard LR. Purified blueberry anthocyanins and blueberry juice alter development of obesity in mice fed an obesogenic high-fat diet. J Agric Food Chem 2010; 58(7):3970-3976.
16. Wu T, Qi X, Guo J, Zhu R, Chen W, Zheng X, Yu T. Dietary supplementation with purified mulberry (Morus australis Poir) anthocyanins suppress body weight gain in high-fat diet fed C57BL/6 mice. Food Chem 2013; 141:482-487.
17. Prior RL, Wu X, Gu L, Hager TJ, Hager A, Howard LR. Whole berries verses berry anthocyanins: interactions with dietary fat levels in the C57BL/6J mouse model of obesity. J Agric Food Chem 2008; 56:647-653.
18. Wu T, Yu Z, Tang Q, Song H, Gao Z, Chen W, Zheng X. Honeysuckle anthocyanin supplementation prevents diet-induced obesity in C57BL/6 mice. Food Funct 2013; 4(11):1654-1661.

19. Roopchand DE, Kuhn P, Rojo LE, Lila MA, Raskin IL. Blueberry polyphenol-enriched soybean flour reduces hyperglycemia, body weight gain and serum cholesterol in mice. Pharmacol Res 2013; 68:59-67.
20. Tsuda T, Horio F, Uchida K, Aoki H, Osawa T. Dietary cyanidin-3-O-beta-D-glucosiderich purple corn color prevents obesity and meliorates hyperglycemia in mice. J Nutr 2003;133:2125-2130.
21. Johnson MH, Lucius A, Meyer T, de Mejia EG. Cultivar evaluation and effect of fermentation on antioxidant capacity and in vitro inhibition of alpha-amylase and alphaglucosidase by Highbush blueberry (Vaccinium corombosum). J Agric Food Chem 2011;59:8923-8930.
22. Johnson MH, de Mejia EG, Fan J, Lila MA, Yousef GG. Anthocyanins and proanthocyanidins from blueberry-blackberry fermented beverages inhibit markers of inflammation in RAW 264.7 macrophages and carbohydrate-utilizing enzymes in vitro. Mol Nutr Food Res 2013; 57:1182-1197.
23. Su MS, Chien PJ. Antioxidant activity, anthocyanins, and phenolics of rabbiteye blueberry (Vaccinium ashei) fluid products as affected by fermentation. Food Chem 2007; 104, 182-187.
24. Martin JL, Matar C. Increase of antioxidant capacity of the lowbush blueberry (Vaccinium angustifolium) during fermentation by a novel bacterium from the fruit microflora. J Sci Food Agric 2005; 85 (9): 1477-1484.
25. Vuong T, Martineau LC, Ramassamy C, Matar C, Haddad PS. Fermented Canadian lowbush blueberry juice stimulates glucose uptake and AMP-activated protein kinase in insulin-sensitive cultured muscle cells and adipocytes. Can J Physiol Pharmacol 2007; 85:956-965.
26. Lim JW, Hwang HJ, Shin CS. Polyphenol compounds and anti-inflammatory activities of Korean black raspberry (Rubus coreanus Miquel) wines produced from juice supplemented with pulp and seed. J Agric Food Chem 2012; 60 (20):5121–5127.
27. Wang JZ, Yousef GG, Rogers RB, de Mejia EG, Raskin I, Lila MA. Maqui Berry (Aristotelia chilensis) juices fermented with yeasts: Effects on phenolic composition, antioxidant capacity, and iNOS and COX-2 Protein Expression. Chapter in: Patil, B. et al.(2012) ACS Symposium Series; American Chemical Society; Washington, D.C. pp. 95-116.

28. Lee J. Determination of total monomeric anthocyanin pigment content of fruit juices, beverages, natural colorants, and wines by the pH differential method: collaborative. J AOAC Int 2005; 88(5):1269-1278.
29. DeFuria, J., Bennett G, Strissel KJ, Perfield II, JW, Milbury PE, Greenberg AS, Obin MS. Dietary blueberry attenuates whole-body insulin resistance in high fat-fed mice by reducing adipocyte death and its inflammatory sequelae. J Nutr 2009; 139:1510-1516.
30. Ayala JE Samuel VT, Morton GJ, Obici S, Croniger CM, Shulman GI, Wasserman DH,McGuinness OP, for the NIH Mouse Metabolic Phenotyping Center Consortium. Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice. Disease Models & Mechanisms 2010; 3:525-534.
31. Abatan OI, Welch KB, Nemzek JA. Evaluation of saphenous venipuncture and modified tail-clip blood collection in mice. J Am Assoc Lab Anim Sci 2008; 47(3):8-15.
32. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28:412-419.
33. Fan J, Johnson MH, Lila MA, Yousef G, de Mejia EG. Berry and citrus phenolic compounds inhibit dipeptidyl peptidase IV, implications in diabetes management. Evid-based Compl Alt Med 2013; No. 479505, dx.doi.org/10.1155/2013/479505.
34. Cattozzo G, Albeni C, Calonaci A, De Luca G. Evaluation of the analytical performance of the Beckman Coulter AU680 automated analytical system based on quality specifications for allowable performance derived from biological variation. Clin Chem Lab Med 2011;49(9):1563-1567.
35. Abramoff MD, Magalhaes PJ, Ram SJ. Image processing with ImageJ. Biophotonics Int 2004; 11(7):36-42.
36. R Development Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing 2013. Vienna, Austria. ISBN 3-900051-07-0, URL http://www.R-project.org/.
37. Smyth GK. Limma: linear models for microarray data. In: Bioinformatics and Computational Biology Solutions using R and Bioconductor, R. Gentleman, V. Carey, S.Dudoit, R. Irizarry, W. Huber (eds.), Springer: 2009.

38. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser 1995; B 57: 289-00.
39. Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009; 4:44–57.
40. Huang DW, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 2009; 37:1–13.
41. Weir GC, Bonner-Weir S. Five stages of evolving β cell dysfunction during progression to diabetes. Diabetes, 2004; 53: S16-S21.
42. Kaiser N, Yuli M, Uçkaya G, Oprescu AI, Berthault MF, Kargar C, Donath MY, Cerasi E,Ktorza A. Dynamic changes in β cell mass and pancreatic insulin during the evolution of nutrition –dependent diabetes in Psammonmy obesus: Impact of glycemic control. Diabetes,2005; 54:138-145.
43. Meijer JJ. Role of reduced β-cell mass versus impaired b-cell function in the pathogenesis of type 2 diabetes. Diabetes Care, 2013; 36, S113-S119.
44. Jongeneel, C. Victor, et al. "An atlas of human gene expression from massively parallel signature sequencing (MPSS)." Genome research 15.7 (2005): 1007-1014.
45. Rojo LE, Ribnicky D, Logendra S, Poulev A, Rojas-Silva P, Kuhn P, Dorn R, Grace MH, Lila MA, Raskin I. In vitro and in vivo anti-diabetic effects of anthocyanins from Maqui Berry (Aristotelia chilensis). Food Chem 2012; 131 (2):387-396.
46. Weisinger RS, Stanley TK, Begg DP, Weisinger HS, Spark KJ, Jois M. Angiotensin converting enzyme inhibition lowers body weight and improves glucose tolerance in C57BL/6J mice maintained on a high fat diet. Physiol Behav 2009; 98(1-2): 192-197.
47. Nam KH, Yong W, Harvat T, Adewola A, Wang S, Oberholzer J, Eddington DT. Sizebased separation and collection of mouse pancreatic islets for functional analysis. Biomed Microdevices 2010; 12(5): 865-874.
48. Benn T, Kim B, Park YK, Wegner CJ, Harness E, Nam TG, Kim DO, Lee JS, Lee JY. Polyphenol-rich blackcurrant extract prevents inflammation in diet-induced obese mice. J Nutr Biochem 2014; 25:1019-1025.
49. Prior RL, Wu X, Gu L, Hager T, Hager A, Wilkes S, Howard L. Purified berry anthocyanins but not whole berries normalize lipid parameters in mice fed an obesogenic high fat diet. Mol Nutr Food Res 2009; 53: 1406–1418.

50. Guo H, Xia M, Zou T, Ling W, Zhong R, Zhang W. Cyanidin-3-glucoside attenuates obesity-associated insulin resistance and hepatic steatosis in high-fat fed and db/db mice via the transcription factor FoxO1. J Nutr Biochem 2012; 23:349-360.
51. Jayaprakasam B, Olson LK, Schutzki RE, Tai MH, Nair MG. Amelioration of obesity and glucose intolerance in high-fat fed C57BL/6 mice by anthocyanins and ursolic acid in Cornelian cherry (Cornus mas). J Agric Food Chem 2006; 54: 243-248.
52. Ennulat D, Magid-Slav M, Rehm S, Tatsuoka KS. Diagnostic performance of traditional hepatobiliary biomarkers of drug-induced liver injury in the rat. Toxicol Sci 2010; 116(2):397-412.
53. Blomme B, Van Steenkiste C, Vanhuysse J, Colle I, Callewaert N, Van Vlierberghe H. Impact of elevation of total bilirubin level and etiology of the liver disease on serum Nglycosylationpatterns in mice and humans. Am J Physiol Gastrointest Liver Physiol 2010;298(5):G615-624.
54. Yogalakshmi B, Sreeja S, Geetha R, Radika MK, Anuradha CV. Grape seed proanthocyanidin rescues rats from steatosis: a comparative and combination study with metformin. J Lipids 2013; ArticleID:152897.
55. Liu Y, Wang D, Zhang D, Lv Y, Wei Y, Wu W, Zhou F, Tang M, Mao T, Li M, Ji B.Inhibitory effect of blueberry polyphenolic compounds on oleic acid-induced hepatic steatosis in vitro. J Agric Food Chem 2011; 59:12254-12263.
56. Wargent ET, O'Dowd JF, Zaibi MS, Gao D, Bing C, Trayhurn P, Cawthorne MA, Arch JR,Stocker CJ. Contrasts between the effects of zinc-α2-glycoprotein, a putative β3/2-adrenoceptor agonist and the β3/2-adrenoceptor agonist BRL35135 in C57Bl/6 (ob/ob) mice.J Endocrinol 2013; 216(2): 157-168.
57. Marshall BA, Tordjman K, Host HH, Ensor NJ, Kwon G, Marshall CA, Coleman T,McDaniel ML, Semenkovich CF. Relative hypoglycemia and hyperinsulinemia in mice with heterozygous lipoprotein lipase (LPL) deficiency. J Biol Chem 1999; 274(39): 27426-27432.
58. Yaney GC, Corkey BE. Fatty acid metabolism and insulin secretion in pancreatic beta cells. Diabetologia 2003; 46:1297–1312.
59. Newsholme P, Keane D, Welters HJ, Morgan NG. Life and death decisions of the pancreatic beta-cell: the role of fatty acids. Clin Sci (Lond) 2007; 112:27–42.

60. Kobayashi M, Kikuchi O, Sasaki T, Kim HJ, Yokota-Hashimoto H, Lee YS, Amano K, Kitazumi T, Susanti VY, Kitamura YI, Kitamura T. FoxO1 as a double-edged sword in the pancreas: analysis of pancreas-and β-cell-specific FoxO1 knockout mice. Am J Physiol Endocrinol Metab 2012; 302(5): E603-E613.
61. Martinez SC, Tanabe K, Cras-Méneur C, Abumrad NA, Bernal-Mizrachi E, Permutt MA. Inhibition of Foxo1 protects pancreatic islet β-cells against fatty acid and endoplasmic reticulum stress–induced apoptosis. Diabetes 2008; 57(4): 846-859.
62. Hong SH, Heo JI, Kim JH, Kwon SO, Yeo KM, Bakowska-Barczak AM, Kolodziejczyk P, Ryu OH, Choi MK, Kang YH, Lim SS, Suh HW, Huh SO, Lee JY. Antidiabetic and beta cell-protection activities of purple corn anthocyanins. Biomol Ther (Seoul) 2013; 21(4):284-289.
63. Valentova K, Vrba J, Bancirova M, Ulrichova J, Kren V. Isoquercetin: Pharmacology,toxicology, and metabolism. Food Chem Tox 2014; 68:267-282
64. Skibola CF, Smith MT. Potential health impacts of excessive flavonoid intake. Free Rad Biol Med 2000; 29(3/4):375-383.
65. Martin KR, Apel CL. Polyphenols as dietary supplements: A double-edged sword. 2010;Nutr Diet Suppl 2:1-12.
66. Galati G, O’Brien PJ. Potential toxicity of flavonoids and other dietary phenolics: Significance for their chemopreventive and anticancer properties. Free Rad Biol Med 2004;37(3):287-303.
67. Lluis L, Muñoz M, Nogués MR, Sánchez-Martos V, Romeu M, Giralt M, Valls J, Solà R.Toxicology evaluation of a procyanidin-rich extract from grape skins and seeds. Food Chem Toxicol 2011; 49:1450-1454.
68. Galati G, Lin A, Sultan, AM, O’Brien P. Cellular and in vivo hepatoxicity caused by green tea phenolics and catechins. Free Rad Biol Med 2006; 40:570-580.
69. Lambert JD, Kennett MJ, Sang S, Reuhl KR, Ju J, Yang CS. Hepatotoxicity of high oral dose (-)-epigallocatechin-3-gallate in mice. Food Chem Toxicol 2010; 48:409-416.

 

Alcohol-free fermented blueberry-blackberry beverage phenolic extract attenuates diet-induced obesity and blood glucose in C57BL/6J mice

Michelle H. Johnson, Matthew Wallig, Diego A. Luna Vital

1Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 2Department of Pathobiology, University of Illinois at Urbana-Champaign, 3Food Science, School of Chemistry, Universidad Autónoma de Querétaro, Querétaro, Qro. 76010, México, 4Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL, 61802.

翻译助手

注:将上面摘要外文内容复制后,点击翻译助手,最后粘贴内容至翻译框内。

国外文献

mail  zghmwhmyj@163.com

国内文献

编辑推荐

联系我们

精选页面

黑莓与高脂血症
黑莓与备孕
健康研究
营养成分
黑莓生长
黑莓历史