Skip to main content

Advertisement

Log in

Oxidative stress induced by high-glucose diet in liver of C57BL/6J mice and its underlying mechanism

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

High glycemic index diet can induce multiple diseases. Many research indicated that oxidative stress played important role in many pathological conditions. However, the impact of gene expression and dietary habit on oxidation process are still less clear. We used high-glucose diet to feed C57BL/6J mice for 4 weeks, measured the redox status, physiological and biochemical changes related to diabetes and consequence of metabolic syndrome (nonalcoholic fatty liver, cardiovascular disease), and detected the expressions of 14,446 genes in liver of C57BL/6J mice with DNA microarray. The results showed high-glucose diet induced elevated fatty acid accumulation in liver, insulin resistance index and higher weight in C57BL/6J mice, which indicated high-glucose diet caused to the initiation and development of diabetes and consequence of metabolic syndrome. The results also showed high-glucose diet induced oxidative stress in liver of C57BL/6J mice, which might the cause of initiation and development of diabetes and consequence of metabolic syndrome. Microarray analysis found expressions of genes related to thiol redox, fatty acid oxidation in peroxisome and cytochrome P450 were significantly changed, indicating system in which non-enzyme antioxidant capacity was impaired and sources from which reactive oxygen species (ROS) generated, which revealed the molecular mechanism of oxidative stress induced by high-glucose diet. We validated our microarray findings by conducting real-time RT–PCR assays on selected genes.

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.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. WHO (2006) World health statistics, 2006. World Health Organization, Geneva, Switzerland

    Google Scholar 

  2. WHO (2000) Diet, nutrition, the prevention of chronic disease. World Health Organ Tech Rep Ser 916:1–149

    Google Scholar 

  3. Barclay AW, Petocz P, Mcmillan-Price J, Flood VM, Prvan T, Mitchell P, Brand-Miller JC (2008) Glycemic index, glycemic load, and chronic disease risk: a meta-analysis of observational studies. Am J Clin Nutr 87:627–637

    CAS  PubMed  Google Scholar 

  4. Le KA, Bortolotti M (2008) Role of dietary carbohydrates and macronutrients in the pathogenesis of nonalcoholic fatty liver disease. Curr Opin Clin Nutr Metab Care 11:477–482

    Article  CAS  PubMed  Google Scholar 

  5. Mulholland HG, Murray LJ, Cardwell CR, Cantwell MM (2008) Dietary glycemic index, glycemic load and endometrial and ovarian cancer risk: a systematic review and meta-analysis. Br J Cancer 99:434–441

    Article  CAS  PubMed  Google Scholar 

  6. Brwonlee M (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54:1615–1625

    Article  Google Scholar 

  7. Ceriello A, Quagliaro L, Piconi L, Assaloni R, Da Ros R, Maier A, Esposito K, Giugliano D (2004) Effect of postprandial hypertriglyceridemia and hyperglycemia on circulating adhesion molecules and oxidative stress generation and the possible role of simvastatin treatment. Diabetes 53:701–710

    Article  CAS  PubMed  Google Scholar 

  8. Mohanty P, Hamouda W, Garg R, Aljada A, Ghanim H, Dandona P (2000) Glucose challenge stimulates reactive oxygen species (ROS) generation by leucocytes. J Clin Endocrinol Metab 85:2970–2973

    Article  CAS  PubMed  Google Scholar 

  9. Sies H (1997) Oxidative stress: oxidants and antioxidants. Exp Physiol 82:291–295

    CAS  PubMed  Google Scholar 

  10. Eriksson JW (2007) Metabolic stress in insulin’s target cells leads to ROS accumulation: a hypothetical common pathway causing insulin resistance. FEBS Lett 581:3734–3742

    Article  CAS  PubMed  Google Scholar 

  11. Holvoet P, Lee DH, Steffes M, Gross M, Jacobs DR (2008) Association between circulating oxidized low-density lipoprotein and incidence of the metabolic syndrome. JAMA 299:2287–2293

    Article  CAS  PubMed  Google Scholar 

  12. Duncan ER, Walker SJ, Ezzat VA, Wheatcroft SB, Li JM, Shah AM, Kearney MT (2007) Accelerated endothelial dysfunction in mild prediabetic insulin resistance: the early role of reactive oxygen species. Am J Physiol Endocrinol Metab 293:E1311–E1319

    Article  CAS  PubMed  Google Scholar 

  13. Du D, Shi YH, Le GW (2009) Microarray analysis of high-glucose diet-induced changes in mRNA expression in jejunums of C57BL/6J mice reveals impairment in digestion, absorption. Mol Biol Rep. doi:10.1007/s11033-009-9622-3

  14. Duseja A, Thumburu KK, Das A, Dhiman PK, Chawla YK, Bhadada S, Bhansali A (2007) Insulin tolerance test is comparable to homeostasis model assessment for insulin resistance in patients with nonalcoholic fatty liver disease. Indian J Gastroenterol 26:170–173

    PubMed  Google Scholar 

  15. Hafner SM, Kennedy E, Gonzalez C, Stern MP, Miettinen H (1996) A prospective analysis of the HOMA model. The Mexico City Diabetes Study. Diabetes Care 19:1138–1141

    Article  Google Scholar 

  16. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with Folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  17. Vaca CE, Wilhelm J, Harms-Rihsdahl M (1988) Interaction of lipid peroxidation product with DNA: a review. Mutat Res Rev Genet Toxicol 195:137–149

    CAS  Google Scholar 

  18. Ohkawa H, Ohishi N, Yagi K (1979) Assay of lipid peroxides in animal tissue by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  CAS  PubMed  Google Scholar 

  19. Raza H, Robin MA, Fang JK, Avadhani NG (2002) Multiple isoforms of mitochondrial glutathione S-transferases and their differential induction under oxidative stress. Biochem J 366:45–55

    CAS  PubMed  Google Scholar 

  20. Tang JJ, Wang MW, Jia EZ, Yan JJ, Wang QM, Zhu J, Yang ZJ, Lu X, Wang LS (2010) The common variant in the GSTM1 and GSTT1 genes is related to markers of oxidative stress and inflammation in patients with coronary artery disease: a case-only study. Mol Biol Rep 37:405–410

    Article  CAS  PubMed  Google Scholar 

  21. Janiszewski M, Lopes LR, Carmo AO, Pedro MA, Brandes RP, Santos CX, Laurindo FR (2005) Regulation of NAD(P)H oxidase by associated protein disulfide isomerase in vascular smooth muscle cells. J Biol Chem 280:40813–40819

    Article  CAS  PubMed  Google Scholar 

  22. Maghdooni Bagheri P, Govaerts I, De Ley M (2010) Role of metallothionein in differentiation of leukemia cells. Mol Biol Rep. 2010 Feb 3. [Epub ahead of print] PMID: 20127519

  23. Thornalley PJ, Vasak M (1985) Possible role for metallothionein in protection against radiation-induced oxidative stress: kinetics and mechanism of its reaction with superoxide and hydroxyl radicals. Biochim Biophys Acta 827:36–44

    CAS  PubMed  Google Scholar 

  24. Bremner I (1987) Nutritional and physiologic significance of metallothionein. Exp Suppl 52:81–107

    CAS  Google Scholar 

  25. Suemori S, Sbimazawa M, Kawase K, Satob M, Nagase H, Yamamoto T, Hara H (2006) Metallothionein, an endogenous antioxidant, protects against retinal neuron damage in mice. Invest Ophthalmol Vis Sci 47:3975–3982

    Article  PubMed  Google Scholar 

  26. Ohgami RS, Campagna DR, McDonald A, Fleming MD (2006) The Steap proteins are metalloreductases. Blood 108:1388–1394

    Article  CAS  PubMed  Google Scholar 

  27. Johnson EF, Palmer GN, Griffin KJ, Hsu MH (1996) Role of the peroxisome proliferator-activated receptor in cytochrome P450 4A gene regulation. FASEB J 10:1241–1248

    CAS  PubMed  Google Scholar 

  28. Mannaerts GP, Van Veldhoven PP, Gastells M (2000) Peroxisome lipid degradation via β- and α-oxidation in mammals. Cell Biochem Biophys 32:73–87

    Article  CAS  PubMed  Google Scholar 

  29. Reddy JK, Hshimoto T (2001) Peroxisomal β-oxidation and peroxisome proliferator-activated receptor: an adaptive metabolic system. Annu Rev Nutr 21:193–230

    Article  CAS  PubMed  Google Scholar 

  30. Li X, Baumqart E, Donq GX, Morrell JC, Jimenez-Sanchez G, Valle D, Smith KD, Gould SJ (2002) PEX11alpha is required for peroxisome proliferation in response to 4-phenylbutyrate but is dispensable for peroxisome proliferator-activated receptor alpha-mediated peroxisome proliferation. Mol Cell Biol 22:8226–8240

    Article  CAS  PubMed  Google Scholar 

  31. Lieber CS (1997) Cytochrome P-4502E1: its physiological and pathological role. Physiol Rev 77:517–544

    CAS  PubMed  Google Scholar 

  32. Ejstrom G, Ingelman-Sundberg M (1989) Rat liver microsomal NADPH-supported oxidase activity and lipid peroxidation dependent on ethanol-inducible cytochrome P-450 (P-450IIE1). Biochem Pharmacol 38:1313–1319

    Article  Google Scholar 

  33. Leclercq IA, Farrell GC, Field J, Bell DR, Gonzalez FJ, Robertson GR (2000) CYP2E1 and CYP4A as microsomal catalysts of lipid peroxides in murine nonalcoholic steatohepatitis. J Clin Invest 105:1067–1075

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by National Natural Science Foundation of China (No. 30571347).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Guo-Wei Le.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 13 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Du, D., Shi, YH. & Le, GW. Oxidative stress induced by high-glucose diet in liver of C57BL/6J mice and its underlying mechanism. Mol Biol Rep 37, 3833–3839 (2010). https://doi.org/10.1007/s11033-010-0039-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-010-0039-9

Keywords

Navigation