Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
권호 표지
DOI QR코드

DOI QR Code

Gamma-tocopherol ameliorates hyperglycemia-induced hepatic inflammation associated with NLRP3 inflammasome in alloxan-induced diabetic mice

  • Lee, Heaji (Department of Food and Nutrition, Kyung Hee University) ;
  • Lim, Yunsook (Department of Food and Nutrition, Kyung Hee University)
  • Received : 2019.01.21
  • Accepted : 2019.05.28
  • Published : 2019.10.01
Download PDF
⟨ Previous Next ⟩

Abstract

BACKGROUND/OBJECTIVES: Hyperglycemia-induced hepatic damage has been recognized as one of the major cause of complications in diabetes. Hepatic complications are associated with inflammation and oxidative stress in diabetes. In this study, we investigated the hypothesis that gamma-tocopherol (GT) supplementation ameliorates NLRP3 inflammasome associated hepatic inflammation in diabetes. MATERIALS/METHODS: Diabetes was induced by the intraperitoneal injection of alloxan (150 mg/kg. BW) in ICR mice. All mice were fed with a control diet (AIN-76A). After diabetes was induced (fasting glucose level ${\geq}250mg/dL$), the mice were treated with tocopherol-stripped corn oil or GT-supplemented (35 mg/kg) corn oil, respectively, by gavage for 2 weeks. RESULTS: GT supplementation reduced fasting blood glucose levels in diabetic mice relative to non-treated diabetic mice. Moreover, GT supplementation ameliorated hyperglycemia-induced hepatic damage by regulation of NOD-like receptor protein 3 (NLRP3)-inflammasome associated inflammation represented by NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain, caspase-1, nuclear $factor-{\kappa}B$ pathway as well as oxidative stress demonstrated by nuclear factor erythroid 2-related factor 2, NAD(P)H dehydrogenase quinone 1, catalase and glutathione-dependent peroxidase in diabetic mice. CONCLUSION: The findings suggested that GT supplementation ameliorated hepatic damage by attenuating inflammation and oxidative stress in alloxan-induced diabetic mice. Taken together, GT could be a beneficial nutrient that can ameliorate inflammatory responses associated with NLRP3 inflammasome in hyperglycemia-induced hepatic damage.

Keywords

References

  1. Pagano E, De Rosa M, Rossi E, Cinconze E, Marchesini G, Miccoli R, Vaccaro O, Bonora E, Bruno G, Observatory AD. The relative burden of diabetes complications on healthcare costs: the populationbased CINECA-SID ARNO Diabetes Observatory. Nutr Metab Cardiovasc Dis 2016;26:944-50. https://doi.org/10.1016/j.numecd.2016.05.002
  2. Regnell SE, Lernmark A. Hepatic steatosis in type 1 diabetes. Rev Diabet Stud 2011;8:454-67. https://doi.org/10.1900/RDS.2011.8.454
  3. Karajamaki AJ, Bloigu R, Kauma H, Kesaniemi YA, Koivurova OP, Perkiomaki J, Huikuri H, Ukkola O. Non-alcoholic fatty liver disease with and without metabolic syndrome: different long-term outcomes. Metabolism 2017;66:55-63. https://doi.org/10.1016/j.metabol.2016.06.009
  4. Maritim AC, Sanders RA, Watkins JB 3rd. Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 2003;17:24-38. https://doi.org/10.1002/jbt.10058
  5. Loboda A, Damulewicz M, Pyza E, Jozkowicz A, Dulak J. Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism. Cell Mol Life Sci 2016;73:3221-47. https://doi.org/10.1007/s00018-016-2223-0
  6. Mohamed J, Nazratun Nafizah AH, Zariyantey AH, Budin SB. Mechanisms of diabetes-induced liver damage: the role of oxidative stress and inflammation. Sultan Qaboos Univ Med J 2016;16:e132-41. https://doi.org/10.18295/squmj.2016.16.02.002
  7. Hu C, Ding H, Li Y, Pearson JA, Zhang X, Flavell RA, Wong FS, Wen L. NLRP3 deficiency protects from type 1 diabetes through the regulation of chemotaxis into the pancreatic islets. Proc Natl Acad Sci U S A 2015;112:11318-23. https://doi.org/10.1073/pnas.1513509112
  8. Abderrazak A, Syrovets T, Couchie D, El Hadri K, Friguet B, Simmet T, Rouis M. NLRP3 inflammasome: from a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases. Redox Biol 2015;4:296-307. https://doi.org/10.1016/j.redox.2015.01.008
  9. Kang HH, Kim IK, Lee HI, Joo H, Lim JU, Lee J, Lee SH, Moon HS. Chronic intermittent hypoxia induces liver fibrosis in mice with diet-induced obesity via TLR4/MyD88/MAPK/NF-kB signaling pathways. Biochem Biophys Res Commun 2017;490:349-55. https://doi.org/10.1016/j.bbrc.2017.06.047
  10. Kauppinen A, Suuronen T, Ojala J, Kaarniranta K, Salminen A. Antagonistic crosstalk between NF-${\kappa}B$ and SIRT1 in the regulation of inflammation and metabolic disorders. Cell Signal 2013;25:1939-48. https://doi.org/10.1016/j.cellsig.2013.06.007
  11. Cao Y, Jiang X, Ma H, Wang Y, Xue P, Liu Y. SIRT1 and insulin resistance. J Diabetes Complications 2016;30:178-83. https://doi.org/10.1016/j.jdiacomp.2015.08.022
  12. Alegre F, Pelegrin P, Feldstein AE. Inflammasomes in liver fibrosis. Semin Liver Dis 2017;37:119-27. https://doi.org/10.1055/s-0037-1601350
  13. Koyama Y, Brenner DA. Liver inflammation and fibrosis. J Clin Invest 2017;127:55-64. https://doi.org/10.1172/JCI88881
  14. Li J, Cordero P, Nguyen V, Oben JA. The role of vitamins in the pathogenesis of non-alcoholic fatty liver disease. Integr Med Insights 2016;11:19-25.
  15. Lee H, Lim Y. Tocotrienol-rich fraction supplementation reduces hyperglycemia-induced skeletal muscle damage through regulation of insulin signaling and oxidative stress in type 2 diabetic mice. J Nutr Biochem 2018;57:77-85. https://doi.org/10.1016/j.jnutbio.2018.03.016
  16. Smolarek AK, Suh N. Chemopreventive activity of vitamin E in breast cancer: a focus on $\gamma$- and $\delta$-tocopherol. Nutrients 2011;3:962-86. https://doi.org/10.3390/nu3110962
  17. Jiang Q, Ames BN. Gamma-tocopherol, but not alpha-tocopherol, decreases proinflammatory eicosanoids and inflammation damage in rats. FASEB J 2003;17:816-22. https://doi.org/10.1096/fj.02-0877com
  18. Shin H, Eo H, Lim Y. Similarities and differences between alphatocopherol and gamma-tocopherol in amelioration of inflammation, oxidative stress and pre-fibrosis in hyperglycemia induced acute kidney inflammation. Nutr Res Pract 2016;10:33-41. https://doi.org/10.4162/nrp.2016.10.1.33
  19. Shin J, Yang SJ, Lim Y. Gamma-tocopherol supplementation ameliorated hyper-inflammatory response during the early cutaneous wound healing in alloxan-induced diabetic mice. Exp Biol Med (Maywood) 2017;242:505-15. https://doi.org/10.1177/1535370216683836
  20. Peh HY, Tan WS, Liao W, Wong WS. Vitamin E therapy beyond cancer: Tocopherol versus tocotrienol. Pharmacol Ther 2016;162:152-69. https://doi.org/10.1016/j.pharmthera.2015.12.003
  21. Himmelfarb J, Kane J, McMonagle E, Zaltas E, Bobzin S, Boddupalli S, Phinney S, Miller G. Alpha and gamma tocopherol metabolism in healthy subjects and patients with end-stage renal disease. Kidney Int 2003;64:978-91. https://doi.org/10.1046/j.1523-1755.2003.00151.x
  22. Uusitalo L, Nevalainen J, Niinisto S, Alfthan G, Sundvall J, Korhonen T, Kenward MG, Oja H, Veijola R, Simell O, Ilonen J, Knip M, Virtanen SM. Serum alpha- and gamma-tocopherol concentrations and risk of advanced beta cell autoimmunity in children with HLA-conferred susceptibility to type 1 diabetes mellitus. Diabetologia 2008;51:773-80. https://doi.org/10.1007/s00125-008-0959-2
  23. Jiang Q, Elson-Schwab I, Courtemanche C, Ames BN. gammatocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells. Proc Natl Acad Sci U S A 2000;97:11494-9. https://doi.org/10.1073/pnas.200357097
  24. Roldi LP, Pereira RV, Tronchini EA, Rizo GV, Scoaris CR, Zanoni JN, Natali MR. Vitamin E (alpha-tocopherol) supplementation in diabetic rats: effects on the proximal colon. BMC Gastroenterol 2009;9:88. https://doi.org/10.1186/1471-230X-9-88
  25. Kim GH, Chung JW, Lee JH, Ok KS, Jang ES, Kim J, Shin CM, Park YS, Hwang JH, Jeong SH, Kim N, Lee DH, Kim JW. Effect of vitamin E in nonalcoholic fatty liver disease with metabolic syndrome: A propensity score-matched cohort study. Clin Mol Hepatol 2015;21:379-86. https://doi.org/10.3350/cmh.2015.21.4.379
  26. Agca CA, Tuzcu M, Hayirli A, Sahin K. Taurine ameliorates neuropathy via regulating NF-${\kappa}B$ and Nrf2/HO-1 signaling cascades in diabetic rats. Food Chem Toxicol 2014;71:116-21. https://doi.org/10.1016/j.fct.2014.05.023
  27. Gupte AA, Lyon CJ, Hsueh WA. Nuclear factor (erythroid-derived 2)-like-2 factor (Nrf2), a key regulator of the antioxidant response to protect against atherosclerosis and nonalcoholic steatohepatitis. Curr Diab Rep 2013;13:362-71. https://doi.org/10.1007/s11892-013-0372-1
  28. Harijith A, Ebenezer DL, Natarajan V. Reactive oxygen species at the crossroads of inflammasome and inflammation. Front Physiol 2014;5:352. https://doi.org/10.3389/fphys.2014.00352
  29. Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, Quagliaro L, Ceriello A, Giugliano D. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation 2002;106:2067-72. https://doi.org/10.1161/01.CIR.0000034509.14906.AE
  30. Li X, Gao Y, Xu H, Hou J, Gao P. Diabetes mellitus is a significant risk factor for the development of liver cirrhosis in chronic hepatitis C patients. Sci Rep 2017;7:9087. https://doi.org/10.1038/s41598-017-09825-7
  31. Rath PC, Aggarwal BB. TNF-induced signaling in apoptosis. J Clin Immunol 1999;19:350-64. https://doi.org/10.1023/A:1020546615229
  32. Ingaramo PI, Ronco MT, Frances DE, Monti JA, Pisani GB, Ceballos MP, Galleano M, Carrillo MC, Carnovale CE. Tumor necrosis factor alpha pathways develops liver apoptosis in type 1 diabetes mellitus. Mol Immunol 2011;48:1397-407. https://doi.org/10.1016/j.molimm.2011.03.015
  33. Carnovale CE, Ronco MT. Role of nitric oxide in liver regeneration. Ann Hepatol 2012;11:636-47. https://doi.org/10.1016/S1665-2681(19)31436-X
  34. Zheng QY, Cao ZH, Hu XB, Li GQ, Dong SF, Xu GL, Zhang KQ. LIGHT/IFN-$\gamma$ triggers $\beta$ cells apoptosis via NF-${\kappa}B$/Bcl2-dependent mitochondrial pathway. J Cell Mol Med 2016;20:1861-71. https://doi.org/10.1111/jcmm.12876
  35. Boumela I, Assou S, Aouacheria A, Haouzi D, Dechaud H, De Vos J, Handyside A, Hamamah S. Involvement of BCL2 family members in the regulation of human oocyte and early embryo survival and death: gene expression and beyond. Reproduction 2011;141:549-61. https://doi.org/10.1530/REP-10-0504
  36. Ju J, Picinich SC, Yang Z, Zhao Y, Suh N, Kong AN, Yang CS. Cancer-preventive activities of tocopherols and tocotrienols. Carcinogenesis 2010;31:533-42. https://doi.org/10.1093/carcin/bgp205
  37. Wree A, Eguchi A, McGeough MD, Pena CA, Johnson CD, Canbay A, Hoffman HM, Feldstein AE. NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation, and fibrosis in mice. Hepatology 2014;59:898-910. https://doi.org/10.1002/hep.26592

Cited by

  1. Protective Role of Loranthus regularis against Liver Dysfunction, Inflammation, and Oxidative Stress in Streptozotocin Diabetic Rat Model vol.2020, 2020, https://doi.org/10.1155/2020/5027986
  2. Hydrogen sulfide mitigates myocardial inflammation by inhibiting nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome activation in diabetic rats vol.245, pp.3, 2019, https://doi.org/10.1177/1535370219899899
  3. Protective effect of exogenous hydrogen sulfide on diaphragm muscle fibrosis in streptozotocin-induced diabetic rats vol.245, pp.14, 2019, https://doi.org/10.1177/1535370220931038
  4. Vitamin E beyond Its Antioxidant Label vol.10, pp.5, 2021, https://doi.org/10.3390/antiox10050634