Skip to main content

Hypolipidemic effect of dietary water-soluble protein extract from chicken: impact on genes regulating hepatic lipid and bile acid metabolism

European Journal of Nutrition volume 54, pages 193–204 (2015)Cite this article

Abstract

Background

Amount and type of dietary protein have been shown to influence blood lipids. The present study aimed to evaluate the effects of a water-soluble fraction of chicken protein (CP) on plasma and hepatic lipid metabolism in normolipidemic rats.

Methods

Male Wistar rats were fed either a control diet with 20 % w/w casein as the protein source, or an experimental diet where casein was replaced with CP at 6, 14, or 20 % w/w for 4 weeks.

Results

Rats fed CP had markedly reduced levels of triacylglycerols (TAG) and cholesterol in both plasma and liver, accompanied by stimulated hepatic mitochondrial fatty acid oxidation and carnitine palmitoyltransferase 2 activity in the 20 % CP group compared to the control group. In addition, reduced activities and gene expression of hepatic enzymes involved in lipogenesis were observed. The gene expression of sterol regulatory element-binding transcription factor 1 was reduced in the 20 % CP-fed rats, whereas gene expression of peroxisome proliferator-activated receptor alpha was increased. Moreover, 6, 14, and 20 % CP-fed rats had significantly increased free carnitine and acylcarnitine plasma levels compared to control rats. The plasma methionine/glycine and lysine/arginine ratios were reduced in 20 % CP-treated rats. The mRNA level of ATP-binding cassette 4 was increased in the 20 % CP group, accompanied by the increased level of plasma bile acids.

Conclusions

The present data suggest that the hypotriglyceridemic property of a water-soluble fraction of CP is primarily due to effects on TAG synthesis and mitochondrial fatty acid oxidation. The cholesterol-lowering effect by CP may be linked to increased bile acid formation.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Abbreviations

ABC:

ATP-binding cassette

Acaca/ACC:

Acetyl-coenzyme A carboxylase alpha

ACE:

Angiotensin-converting enzyme

AST:

Alanine aminotransferase

ALT:

Aspartate aminotransferase

CP:

Chicken protein

CPT:

Carnitine palmitoyltransferase

CV:

Coefficient of variation

Fasn/FAS:

Fatty acid synthase

GPAT:

Glycerol-3-phosphate acyltransferase

HDL:

High-density lipoprotein

HMG-CoA reductase:

3-hydroxy-3-methylglutaryl-coenzyme A reductase

HMG-CoA synthase:

3-hydroxy-3-methylglutaryl-coenzyme A synthase

LDL:

Low-density lipoprotein

MUFA:

Monounsaturated fatty acid

NAFLD:

Nonalcoholic fatty liver disease

NEFA:

Nonesterified fatty acid

PC:

Phospholipid phosphatidylcholine

PL:

Phospholipid

PPARα:

Peroxisome proliferator-activated receptor alpha

PUFA:

Polyunsaturated fatty acid

SFA:

Saturated fatty acid

Srebf/SREBP:

Sterol regulatory element-binding transcription factor

TAG:

Triacylglycerol

T2DM:

Type 2 diabetes mellitus

VLDL:

Very-low-density lipoprotein

References

  1. Ren J, Pulakat L, Whaley-Connell A, Sowers JR (2010) Mitochondrial biogenesis in the metabolic syndrome and cardiovascular disease. J Mol Med (Berl) 88:993–1001

    Article  CAS  Google Scholar 

  2. Subramanian S, Chait A (2012) Hypertriglyceridemia secondary to obesity and diabetes. Biochim Biophys Acta 1821:819–825

    Article  CAS  Google Scholar 

  3. Burri L, Thoresen GH, Berge RK (2010) The role of PPARalpha activation in liver and muscle. PPAR Res. doi:10.1155/2010/542359

  4. Rakhshandehroo M, Knoch B, Müller M, Kersten S (2010) Peroxisome Proliferator-activated receptor alpha target genes. PPAR Research, Vol 2010, Article ID 612089. doi:10.1155/2010/612089

  5. Eberle D, Hegarty B, Bossard P, Ferre P, Foufelle F (2004) SREBP transcription factors: master regulators of lipid homeostasis. Biochimie 86:839–848

    Article  CAS  Google Scholar 

  6. 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  Google Scholar 

  7. Ascencio C, Torres N, Isoard-Acosta F, Gomez-Perez FJ, Hernandez-Pando R, Tovar AR (2004) Soy protein affects serum insulin and hepatic SREBP-1 mRNA and reduces fatty liver in rats. J Nutr 134:522–529

    CAS  Google Scholar 

  8. Moriyama T, Kishimoto K, Nagai K, Urade R, Ogawa T, Utsumi S, Maruyama N, Maebuchi M (2004) Soybean beta-conglycinin diet suppresses serum triglyceride levels in normal and genetically obese mice by induction of beta-oxidation, downregulation of fatty acid synthase, and inhibition of triglyceride absorption. Biosci Biotechnol Biochem 68:352–359

    Article  CAS  Google Scholar 

  9. Velasquez MT, Bhathena SJ (2007) Role of dietary soy protein in obesity. Int J Med Sci 4:72–82

    Article  CAS  Google Scholar 

  10. Choi JY, Jeon JE, Jang SY, Jeong YJ, Jeon SM, Park HJ, Choi MS (2011) Differential effects of powdered whole soy milk and its hydrolysate on antiobesity and antihyperlipidemic response to high-fat treatment in C57BL/6 N mice. J Agric Food Chem 59:2584–2591

    Article  CAS  Google Scholar 

  11. Lee YP, Mori TA, Puddey IB, Sipsas S, Ackland TR, Beilin LJ, Hodgson JM (2009) Effects of lupin kernel flour-enriched bread on blood pressure: a controlled intervention study. Am J Clin Nutr 89:766–772

    Article  CAS  Google Scholar 

  12. Rigamonti E, Parolini C, Marchesi M, Diani E, Brambilla S, Sirtori CR, Chiesa G (2010) Hypolipidemic effect of dietary pea proteins: impact on genes regulating hepatic lipid metabolism. Mol Nutr Food Res 54(Suppl 1):S24–S30

    Article  CAS  Google Scholar 

  13. Wergedahl H, Liaset B, Gudbrandsen OA, Lied E, Espe M, Muna Z, Mork S, Berge RK (2004) Fish protein hydrolysate reduces plasma total cholesterol, increases the proportion of HDL cholesterol, and lowers acyl-CoA: cholesterol acyltransferase activity in liver of Zucker rats. J Nutr 134:1320–1327

    CAS  Google Scholar 

  14. Gudbrandsen OA, Wergedahl H, Liaset B, Espe M, Mork S, Berge RK (2008) Dietary single cell protein reduces fatty liver in obese Zucker rats. Br J Nutr 100:776–785

    Article  CAS  Google Scholar 

  15. Zhang Y, Kouguchi T, Shimizu M, Ohmori T, Takahata Y, Morimatsu F (2010) Chicken collagen hydrolysate protects rats from hypertension and cardiovascular damage. J Med Food 13:399–405

    Article  CAS  Google Scholar 

  16. Saiga A, Iwai K, Hayakawa T, Takahata Y, Kitamura S, Nishimura T, Morimatsu F (2008) Angiotensin I-converting enzyme-inhibitory peptides obtained from chicken collagen hydrolysate. J Agric Food Chem 56:9586–9591

    Article  CAS  Google Scholar 

  17. Morita T, Oh-hashi A, Takei K, Ikai M, Kasaoka S, Kiriyama S (1997) Cholesterol-lowering effects of soybean, potato and rice proteins depend on their low methionine contents in rats fed a cholesterol-free purified diet. J Nutr 127:470–477

    CAS  Google Scholar 

  18. Bjorndal B, Berge C, Ramsvik MS, Svardal A, Bohov P, Skorve J, Berge RK (2013) A fish protein hydrolysate alters fatty acid composition in liver and adipose tissue and increases plasma carnitine levels in a mouse model of chronic inflammation. Lipids Health Dis 12:143

    Article  Google Scholar 

  19. Grimstad T, Bjørndal B, Cacabelos D, Aasprong OG, Omdal R, Svardal A, Bohov P, Pamplona R, Portero-Otin M, Berge RK, Hausken T (2013) A salmon peptide diet alleviates experimental colitis as compared with fish oil. J Nutr Sci 2:1–8

    Article  Google Scholar 

  20. Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37:911–917

    Article  CAS  Google Scholar 

  21. Bjorndal B, Vik R, Brattelid T, Vigerust NF, Burri L, Bohov P, Nygard O, Skorve J, Berge RK (2012) Krill powder increases liver lipid catabolism and reduces glucose mobilization in tumor necrosis factor-alpha transgenic mice fed a high-fat diet. Metabolism 61:1461–1472

    Article  Google Scholar 

  22. Vernez L, Wenk M, Krahenbuhl S (2004) Determination of carnitine and acylcarnitines in plasma by high-performance liquid chromatography/electrospray ionization ion trap tandem mass spectrometry. Rapid Commun Mass Spectrom 18:1233–1238

    Article  CAS  Google Scholar 

  23. Vigerust NF, Bohov P, Bjorndal B, Seifert R, Nygard O, Svardal A, Glintborg D, Berge RK, Gaster M (2012) Free carnitine and acylcarnitines in obese patients with polycystic ovary syndrome and effects of pioglitazone treatment. Fertil Steril 98:1620–1626

    Article  CAS  Google Scholar 

  24. Cohen SA, Strydom DJ (1988) Amino acid analysis utilizing phenylisothiocyanate derivatives. Anal Biochem 174:1–16

    Article  CAS  Google Scholar 

  25. Liaset B, Julshamn K, Espe M (2003) Chemical composition and theoretical nutritional evaluation of the produced fractions from enzymic hydrolysis of salmon frames with Protamex (TM). Proc Biochem 38:1747–1759

    Google Scholar 

  26. Bremer J (1981) The effect of fasting on the activity of liver carnitine palmitoyltransferase and its inhibition by malonyl-coa. Biochim Biophys Acta 665:628–631

    Article  CAS  Google Scholar 

  27. Madsen L, Rustan AC, Vaagenes H, Berge K, Dyroy E, Berge RK (1999) Eicosapentaenoic and docosahexaenoic acid affect mitochondrial and peroxisomal fatty acid oxidation in relation to substrate preference. Lipids 34:951–963

    Article  CAS  Google Scholar 

  28. Skorve J, Al-Shurbaji A, Asiedu D, Bjorkhem I, Berglund L, Berge RK (1993) On the mechanism of the hypolipidemic effect of sulfur-substituted hexadecanedioic acid (3-thiadicarboxylic acid) in normolipidemic rats. J Lipid Res 34:1177–1185

    CAS  Google Scholar 

  29. Vigerust NF, Cacabelos D, Burri L, Berge K, Wergedahl H, Christensen B, Portero-Otin M, Viste A, Pamplona R, Berge RK, Bjørndal B (2011) Fish oil and 3-thia fatty acid have additive effects on lipid metabolism but antagonistic effects on oxidative damage when fed to rats for 50 weeks. J Nutr Biochem 23:1384–1393

    Article  Google Scholar 

  30. Rekawiecki R, Rutkowska J, Kotwica J (2012) Identification of optimal housekeeping genes for examination of gene expression in bovine corpus luteum. Reprod Biol 12:362–367

    Article  Google Scholar 

  31. Onyeali EU, Onwuchekwa AC, Monaga CC, Monanu MO (2010) Plasma lipid profile of Wistar albino rats fed palm oil-supplemented diets. Int J Biol Chem Sci 4:1163–1169

    Google Scholar 

  32. Liaset B, Madsen L, Qin Haob GC, Mellgrenc G, Marschall H-U, Hallenborg P, Espea M, Frøylanda L, Kristiansen K (2009) Fish protein hydrolysate elevates plasma bile acids and reduces visceral adipose tissue mass in rats. Biochim Biophys Acta Mol Cell Biol Lipid 1791:254–262

    Article  CAS  Google Scholar 

  33. Trauner M, Halilbasic E (2011) Nuclear receptors as new perspective for the management of liver diseases. Gastroenterology 140(1120–1125):e1112

    Google Scholar 

  34. Zhang Y, Kouguchi T, Shimizu K, Sato M, Takahata Y, Morimatsu F (2010) Chicken collagen hydrolysate reduces proinflammatory cytokine production in C57BL/6.KOR-ApoEshl mice. J Nutr Sci Vitaminol (Tokyo) 56:208–210

    Article  CAS  Google Scholar 

  35. Flowers MT (2009) The delta9 fatty acid desaturation index as a predictor of metabolic disease. Clin Chem 55:2071–2073

    Article  CAS  Google Scholar 

  36. Hoppel C (2003) The role of carnitine in normal and altered fatty acid metabolism. Am J Kidney Dis 41:S4–S12

    Article  CAS  Google Scholar 

  37. Lysiak W, Toth PP, Suelter CH, Bieber LL (1986) Quantitation of the efflux of acylcarnitines from rat heart, brain, and liver mitochondria. J Biol Chem 261:13698–13703

    CAS  Google Scholar 

  38. Dikkers A, Tietge UJ (2010) Biliary cholesterol secretion: more than a simple ABC. World J Gastroenterol 16:5936–5945

    CAS  Google Scholar 

  39. Belinsky MG, Bain LJ, Balsara BB, Testa JR, Kruh GD (1998) Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT subfamily of transporter proteins. J Natl Cancer Inst 90:1735–1741

    Article  CAS  Google Scholar 

  40. Gatchalian-Yee M, Arimura Y, Ochiai E, Yamada K, Sugano M (1997) Soybean protein lowers serum cholesterol levels in hamsters: effect of debittered undigested fraction. J Nutr 13:633–639

    Google Scholar 

  41. Sugano M, Goto S, Yamada Y, Yoshida K, Hashimoto Y, Matsuo T, Kimoto M (1988) The hypocholesterolemic action of the undigested fraction of soybean protein in rats. Atherosclerosis 72:115–122

    Google Scholar 

  42. Angelin B, Einarsson K, Leijd B (1978) Effect of chenodeoxycholic acid on serum and biliary lipids in patients with hyperlipoproteinaemia. Clin Sci Mol Med 54:451–455

    CAS  Google Scholar 

  43. Watanabe M, Houten SM, Wang L, Moschetta A, Mangelsdorf DJ, Heyman RA, Moore DD, Auwerx J (2004) Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. J Clin Invest 113:1408–1418

    Article  CAS  Google Scholar 

  44. Gudbrandsen OA, Wergedahl H, Liaset B, Espe M, Berge RK (2005) Dietary proteins with high isoflavone content or low methionine-glycine and lysine-arginine ratios are hypocholesterolaemic and lower the plasma homocysteine level in male Zucker fa/fa rats. Br J Nutr 94:321–330

    Article  CAS  Google Scholar 

  45. Xu YJ, Arneja AS, Tappia PS, Dhalla NS (2008) The potential health benefits of taurine in cardiovascular disease. Exp Clin Cardiol 13:57–65

    Google Scholar 

  46. Kritchevsky D, Tepper SA, Czarnecki SK, Klurfeld DM (1982) Atherogenicity of animal and vegetable protein: influence of the lysine to arginine ratio. Atherosclerosis 41:429–431

    Article  CAS  Google Scholar 

  47. Vega-Lopez S, Matthan NR, Ausman LM, Harding SV, Rideout TC, Ai M, Otokozawa S, Freed A, Kuvin JT, Jones PJ, Schaefer EJ, Lichtenstein AH (2010) Altering dietary lysine: arginine ratio has little effect on cardiovascular risk factors and vascular reactivity in moderately hypercholesterolemic adults. Atherosclerosis 210:555–562

    Article  CAS  Google Scholar 

  48. Moundras C, Remesy C, Levrat MA, Demigne C (1995) Methionine deficiency in rats fed soy protein induces hypercholesterolemia and potentiates lipoprotein susceptibility to peroxidation. Metabolism 44:1146–1152

    Article  CAS  Google Scholar 

  49. Barakat HA, Hamza AH (2012) Glycine alleviates liver injury induced by deficiency in methionine and or choline in rats. Eur Rev Med Pharmacol Sci 16:728–736

    CAS  Google Scholar 

Download references

Acknowledgments

We thank Kari Williams, Liv Kristine Øysæd, Randi Sandvik, Kari Helland Mortensen, Svein Krüger and Torunn Eide for technical assistance, and Eline Milde and the staff at the Laboratory Animal Facility, University of Bergen, for care of the animals. This project has been founded by the University of Bergen through the Clinical Nutrition Program and the company Norilia AS.

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Department of Clinical Science, University of Bergen, 5020, Bergen, Norway

    Rita Vik, Bodil Bjørndal, Pavol Bohov, Asbjørn Svardal, Ottar K. Nygård, Jan E. Nordrehaug, Jon Skorve & Rolf K. Berge

  2. National Institute of Nutrition and Seafood Research, NIFES, 5817, Bergen, Norway

    Trond Brattelid

  3. Department of Heart Disease, Haukeland University Hospital, 5021, Bergen, Norway

    Ottar K. Nygård & Rolf K. Berge

Authors
  1. Rita Vik
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bodil Bjørndal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pavol Bohov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Trond Brattelid
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Asbjørn Svardal
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ottar K. Nygård
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jan E. Nordrehaug
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jon Skorve
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Rolf K. Berge
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rita Vik.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Vik, R., Bjørndal, B., Bohov, P. et al. Hypolipidemic effect of dietary water-soluble protein extract from chicken: impact on genes regulating hepatic lipid and bile acid metabolism. Eur J Nutr 54, 193–204 (2015). https://doi.org/10.1007/s00394-014-0700-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-014-0700-5

Keywords

  • Chicken protein
  • Lipogenesis
  • β-Oxidation