Skip to main content
SpringerLink
Log in

Effects of dietary fat and oxidized cholesterol on gene expression in rat liver as assessed by cDNA expression array analysis

  • ORIGINAL CONTRIBUTION
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Summary

Background

Specific oxysterols acting as ligands for nuclear transcription factors were shown to affect expression of genes involved in lipid metabolism. However, the various biological effects of oxysterols such as cytotoxicity, atherogenicity or mutagenicity suggest that other genes may be also affected by oxysterols than lipid metabolism.

Aim of the study

The present study was conducted to investigate the effects of dietary oxidized cholesterol containing significant amounts of oxysterols and its interactions with different dietary fats on gene expression profiles as assessed by DNA array technology in rats.

Methods

54 male Sprague–Dawley rats were assigned to six groups and were fed six semisynthetic diets, which varied in the type of dietary fat (coconut oil vs. salmon oil) and dietary cholesterol (none cholesterol vs. 5 g unoxidized cholesterol/kg vs. 5 g oxidized cholesterol/kg).

Results

Changes in gene expression as observed in response to dietary oxidized cholesterol were strongly dependent on the type of fat. In the rats fed coconut oil, the expression of 7 genes (5 up– and 2 down–regulated) was altered by dietary oxidized cholesterol, while in the rats fed salmon oil, the expression of 50 genes (16 up– and 34 down–regulated) was altered. 29 genes (22 up- and 7 down–regulated) were identified as possible targets for an altered gene expression by dietary salmon oil as compared to dietary coconut oil.

Conclusion

The present study showed that dietary oxidized cholesterol transcriptionally affects many genes involved in xenobiotic metabolism and stress response—an effect that was amplified by the administration of fish oil as dietary fat.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Jump DB (2002) Dietary polyunsaturated fatty acids and regulation of gene transcription. Curr Opin Lipidol 13:155–164

    Article  CAS  PubMed  Google Scholar 

  2. Ntambi JM (1999) Regulation of stearoyl–CoA desaturase by polyunsaturated fatty acids and cholesterol. J Lipid Res 40:1549–1558

    CAS  PubMed  Google Scholar 

  3. Peet DJ, Janowski BA, Mangelsdorf DJ (1998) The LXRs: a new class of oxysterol receptors. Curr Opin Genet Dev 8:571–575

    Article  CAS  PubMed  Google Scholar 

  4. Venkateswaran A, Repa JJ, Lobaccaro JM, Bronson A, Mangelsdorf DJ, Edwards PA (2000) Human white/murine ABC8 mRNA levels are highly induced in lipid–loaded macrophages. A transcriptional role for specific oxysterols. J Biol Chem 275:14700–14707

    CAS  PubMed  Google Scholar 

  5. Jump DB, Thelen A, Ren B, Mater M (1999) Multiple mechanisms for polyunsaturated fatty acid regulation of hepatic gene transcription. Prostaglandins Leukot Essent Fatty Acids 60:345–349

    CAS  PubMed  Google Scholar 

  6. Kim HJ, Takahashi M, Ezaki O (1999) Fish oil feeding decreases mature sterol regulatory element–binding protein 1 (SREBP-1) by down–regulation of SREBP-1c mRNA in mouse liver. A possible mechanism for down–regulation of lipogenic enzyme mRNAs. J Biol Chem 274:25892–25898

    CAS  PubMed  Google Scholar 

  7. Edwards PA, Kennedy MA, Mak PA (2002) LXRs; oxysterol-activated nuclear receptors that regulate genes controlling lipid homeostasis. Vascul Pharmacol 38:249–256

    Article  CAS  PubMed  Google Scholar 

  8. Horton JD (2002) Sterol regulatory element–binding proteins: transcriptional activators of lipid synthesis. Biochem Soc Trans 30:1091–1095

    CAS  PubMed  Google Scholar 

  9. Osborne TF (2000) Sterol regulatory element- binding proteins (SREBPs): key regulators of nutritional homeostasis and insulin action. J Biol Chem 275:32379–32382

    Article  CAS  PubMed  Google Scholar 

  10. Millatt LJ, Bocher V, Fruchart JC, Staels B (2003) Liver X receptors and the control of cholesterol homeostasis: potential therapeutic targets for the treatment of atherosclerosis. Biochim Biophys Acta 1631:107–118

    CAS  PubMed  Google Scholar 

  11. Endo Y, Fu Z, Abe K, Arai S, Kato H (2002) Dietary protein quantity and quality affect rat hepatic gene expression. J Nutr 132:3632–3637

    CAS  PubMed  Google Scholar 

  12. Fischer A, Pallauf J, Gohil K, Weber SU, Packer L, Rimbach G (2001) Effect of selenium and vitamin E deficiency on differential gene expression in rat liver. Biochem Biophys Res Commun 285:470–475

    Article  CAS  PubMed  Google Scholar 

  13. Song F, Srinivasan M, Aalinkeel R, Patel MS (2001) Use of a cDNA array for the identification of genes induced in islets of suckling rats by a high–carbohydrate nutritional intervention. Diabetes 50:2053–2060

    CAS  PubMed  Google Scholar 

  14. Tom Dieck H, Döring F, Roth HP, Daniel H (2003) Changes in rat hepatic gene expression in response to zinc deficiency as assessed by DNA arrays. J Nutr 133:1004–1010

    CAS  PubMed  Google Scholar 

  15. Vine DF, Croft KD, Beilin LJ, Mamo JC (1997) Absorption of dietary cholesterol oxidation products and incorporation into rat lymph chylomicrons. Lipids 32:887–893

    CAS  PubMed  Google Scholar 

  16. Osada K, Kodama T, Yamada K, Nakamura S, Sugano M (1998) Dietary oxidized cholesterol modulates cholesterol metabolism and linoleic acid desaturation in rats fed high–cholesterol diets. Lipids 33:757–764

    CAS  PubMed  Google Scholar 

  17. Flader D, Brandsch C, Hirche F, Eder K (2003) Effects of megadoses of dietary vitamin E on the antioxidant status of rats fed lard or salmon oil. Int J Vitam Nutr Res 73:275–283

    CAS  PubMed  Google Scholar 

  18. Bansal G, Singh U, Bansal MP (2001) Effect of 7beta–hydroxycholesterol on cellular redox status and heat shock protein 70 expression in macrophages. Cell Physiol Biochem 11:241–246

    CAS  PubMed  Google Scholar 

  19. Ringseis R, Eder K (2003) Effects of dietary fish oil and oxidized cholesterol on the concentration of 7β–hydroxycholesterol in liver, plasma, low density lipoproteins and erythrocytes of rats at various vitamin E supply. Eur J Lipid Sci Technol 105:121–129

    CAS  Google Scholar 

  20. Mori TA, Croft KD, Puddey IB, Beilin LJ (1996) Analysis of native and oxidized low–density lioprotein oxysterols using gas chromatography–mass spectrometry with selective ion monitoring. Redox Report 2:25–34

    CAS  Google Scholar 

  21. Hara A, Radin NS (1978) Lipid extraction of tissues with a low toxicity solvent. Anal Biochem 90:420–426

    Article  CAS  PubMed  Google Scholar 

  22. Association of Official Analytical Chemists (1980) In: Horwitz H (ed) Official Methods of Analysis. 13th ed. Airlington: VA, pp 440–441

  23. Balz MK, Schulte E, Their HP (1993) Simultaneous determination of tocopherol acetate, tocopherols and tocotrienols by HPLC with fluorescence detection in foods. Fat Sci Technol 95:215–220

    CAS  Google Scholar 

  24. Brandsch C, Ringseis R, Eder K (2002) High dietary iron concentrations enhance the formation of cholesterol oxidation products in the liver of adult rats fed salmon oil with minimal effects on antioxidant status. J Nutr 132:2263–2269

    CAS  PubMed  Google Scholar 

  25. Ross MA (1994) Determination of ascorbic acid and uric acid in plasma by high–performance liquid chromatography. J Chromatogr B Biomed Appl 657:197–200

    Article  CAS  PubMed  Google Scholar 

  26. Sülzle A, Hirche F, Eder K (2004) Thermally oxidized fat up–regulates the expression of target genes of PPARα in rat liver. J Nutr 134:1375–1383

    PubMed  Google Scholar 

  27. Eder K, Schleser S, Becker K, Körting R (2003) Conjugated linoleic acids lower release of eicosanoids and nitric oxide from human aortic endothelial cells. J Nutr 133:4083–4089

    CAS  PubMed  Google Scholar 

  28. Pfaffl MW, Gerstmayer B, Bosio A, Windisch W (2003) Effect of zinc deficiency on the mRNA expression pattern in liver and jejunum of adult rats: Monitoring gene expression using cDNA microarrays combined with real–time RT–PCR. J Nutr Biochem 14:691–702

    Article  CAS  PubMed  Google Scholar 

  29. Yaqoob P, Sherrington EJ, Jeffery NM, Sanderson P, Harvey DJ, Newsholme EA, Calder PC (1995) Comparison of the effects of a range of dietary lipids upon serum and tissue lipid composition in the rat. Int J Biochem Cell Biol 27:297–310

    Article  CAS  PubMed  Google Scholar 

  30. Hostmark AT, Lystad E, Huag A, Eilersten E (1989) Plasma lipids, lipoproteins, and fecal excretion of neutral sterols and bile acids in rats fed various high fat diets or a low fat/high sucrose diet. J Nutr 119:356–363

    CAS  PubMed  Google Scholar 

  31. DeSchrijver R, Vermeulen D, Viane E (1991) Lipid metabolism responses in rats fed beef tallow, native or randomised fish oil and native or randomised peanut oil. J Nutr 121:948–955

    CAS  PubMed  Google Scholar 

  32. Farwer SR, der Boer BC, Haddeman E, Kivits GA, Wiersma A, Danse BH (1994) The vitamin E nutritional status of rats fed on diets high in fish oil, linseed oil or sunflower seed oil. Br J Nutr 72:127–145

    CAS  PubMed  Google Scholar 

  33. Roman RJ, Maier KG, Sun CW, Harder DR, Alonso-Galicia M (2000) Renal and cardiovascular actions of 20-hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids. Clin Exp Pharmacol Physiol 27:855–865

    CAS  PubMed  Google Scholar 

  34. Takahashi M, Tsuboyama–Kasaoka N, Nakatani T, Ishii M, Tsutsumi S, Aburatani H, Ezaki O (2002) Fish oil feeding alters liver gene expressions to defend against PPARalpha activation and ROS production. Am J Physiol Gastrointest Liver Physiol 282:G338–G348

    CAS  PubMed  Google Scholar 

  35. Berthou L, Saladin R,Yaqoob P, Branellec D, Calder P, Fruchart JC, Denefle P, Auwerx J, Staels B (1995) Regulation of rat liver apolipoprotein A-I, apolipoprotein A-II and acyl-coenzyme A oxidase gene expression by fibrates and dietary fatty acids. Eur J Biochem 232:179–187

    Article  CAS  PubMed  Google Scholar 

  36. Strobl W, Knerer B, Gratzl R, Arbeiter K, Lin-Lee YC, Patsch W (1993) Altered regulation of apolipoprotein A-IV gene expression in the liver of the genetically obese Zucker rat. J Clin Invest 92: 1766–1773

    CAS  PubMed  Google Scholar 

  37. Osada K, Inoue T, Nakamura S, Sugano M (1999) Dietary soybean protein moderates the deleterious disturbance of lipid metabolism caused by exogenous oxidized cholesterol in rats. Biochim Biophys Acta 1427:337–350

    CAS  PubMed  Google Scholar 

  38. Waxman DJ, Azaroff L (1992) Phenobarbital induction of cytochrome P–450 gene expression. Biochem J 281: 577–592

    CAS  PubMed  Google Scholar 

  39. Albano E, Clot P, Morimoto M, Tomasi A, Ingelman-Sundberg M, French SW (1996) Role of cytochrome P4502E1- dependent formation of hydroxyethyl free radical in the development of liver damage in rats intragastrically fed with ethanol. Hepatology 23:155–163

    CAS  PubMed  Google Scholar 

  40. Osada K, Kodama T, Yamada K, Nakamura S, Sugano M (1998) Dietary oxidized cholesterol modulates cholesterol metabolism and linoleic acid desaturation in rats fed high–cholesterol diets. Lipids 33:757–764

    CAS  PubMed  Google Scholar 

  41. Yee S, Choi BH (1994) Methylmercury poisoning induces oxidative stress in the mouse brain. Exp Mol Pathol 60:188–196

    Article  CAS  PubMed  Google Scholar 

  42. Grune T, Merker K, Sandig G, Davies KJ (2003) Selective degradation of oxidatively modified protein substrates by the proteasome. Biochem Biophys Res Commun 305:709–718

    CAS  PubMed  Google Scholar 

  43. Tontonoz P, Mangelsdorf DJ (2003) Liver x receptor signaling pathways in cardiovascular disease. Mol Endocrinol 17:985–993

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Ernährungswissenschaften, Martin-Luther-Universität Halle-Wittenberg, Emil-Abderhalden-Strasse 26, 06108, Halle/Saale, Germany

    R. Ringseis & K. Eder

Authors
  1. R. Ringseis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. Eder
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K. Eder.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ringseis, R., Eder, K. Effects of dietary fat and oxidized cholesterol on gene expression in rat liver as assessed by cDNA expression array analysis. Eur J Nutr 44, 231–241 (2005). https://doi.org/10.1007/s00394-004-0515-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-004-0515-x

Key words

Search

Navigation