Dietary fatty acids affecting hepatic metabolism and atherosclerosis – mechanisms unravelled using a proteomics approach


  • Guillermo Rodríguez Gutiérrez Rowett Research Institute, Division of Vascular Health
  • Baukje de Roos Rowett Research Institute, Division of Vascular Health



Atherosclerosis, Dietary fatty acids, Extra virgin olive oils, Hepatic lipid metabolism, Proteomics


Dietary fatty acids play an important role in the aetiology of coronary heart disease. The effects of dietary fatty acids on lipoprotein metabolism are well described, but additional or alternative mechanisms relating to potential influence on coronary heart disease are not known. This review describes how proteomics techniques have been used to identify proteins that are differentially regulated by dietary fatty acids. Such proteins may reveal pathways by which dietary fatty acids influence disease risk.


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American Heart Association. 2008. Heart and Stroke Statistical Update.

Arbones-Mainar JM, Ross K, Rucklidge GJ, Reid M, Duncan G, Arthur JR, Horgan GW, Navarro MA, Carnicer R, Arnal C, Osada J, Roos BD. 2007. Extra Virgin Olive Oils Increase Hepatic Fat Accumulation and Hepatic Antioxidant Protein Levels in APOE(-/-) Mice. J. Proteome. Res. 6, 4041-4054. doi:10.1021/pr070321a PMid:17845022

Barnes S, Kim H. 2004. Nutriproteomics: identifying the molecular targets of nutritive and non-nutritive components of the diet. J. Biochem. Mol. Biol. 37, 59-74.

Clement L, Poirier H, Niot I, Bocher V, Guerre-Millo M, Krief S, Staels B, Besnard P. 2002. Dietary trans-10,cis-12 conjugated linoleic acid induces hyperinsulinemia and fatty liver in the mouse. J. Lipid Res. 43, 1400-1409. doi:10.1194/jlr.M20008-JLR200

Daviglus ML, Stamler J, Orencia AJ, Dyer AR, Liu K, Greenland P, Walsh MK, Morris D, Shekelle RB. 1997. Fish consumption and the 30-year risk of fatal myocardial infarction. N. Engl. J. Med. 336, 10461053. doi:10.1056/NEJM199704103361502 PMid:9091800

de Lorgeril M, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N. 1999. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Circulation 99, 779-785.

de Roos B, Duivenvoorden I, Rucklidge G, Reid M, Ross K, Lamers RJ, Voshol PJ, Havekes LM, Teusink B. 2005a. Response of apolipoprotein E*3-Leiden transgenic mice to dietary fatty acids: combining liver proteomics with physiological data. FASEB J 19, 813-815.

de Roos B, Geelen A, Ross K, Rucklidge G, Reid M, Duncan G, Caslake M, Horgan G, Brouwer IA. 2008. Identification of potential serum biomarkers of inflammation and lipid modulation that are altered by fish oil supplementation in healthy volunteers. Proteomics 8, 1965-1974. doi:10.1002/pmic.200700457 PMid:18491311

de Roos B, Rucklidge G, Reid M, Ross K, Duncan G, Navarro MA, Arbones-Mainar JM, Guzman-Garcia MA, Osada J, Browne J, Loscher CE, Roche HM. 2005b. Divergent mechanisms of cis9, trans11-and trans10, cis12-conjugated linoleic acid affecting insulin resistance and inflammation in apolipoprotein E knockout mice: a proteomics approach. FASEB J 19, 1746-1748.

Degrace P, Demizieux L, Gresti J, Chardigny JM, Sebedio JL, Clouet P. 2003. Association of liver steatosis with lipid oversecretion and hypotriglyceridaemia in C57BL/6j mice fed trans-10,cis-12-linoleic acid. FEBS Lett 546, 335-339. doi:10.1016/S0014-5793(03)00610-0 PMid:12832064

den Boer M, Voshol PJ, Kuipers F, Havekes LM, Romijn JA. 2004. Hepatic steatosis: a mediator of the metabolic syndrome. Lessons from animal models. Arterioscler Thromb. Vasc. Biol. 24, 644-649. doi:10.1161/01.ATV.0000116217.57583.6e

Ferro-Luzzi A,Branca F. 1995. Mediterranean diet, Italianstyle: prototype of a healthy diet. Am. J. Clin. Nutr. 61, 1338S-1345S.

Fuchs D, Winkelmann I, Johnson IT, Mariman E, Wenzel U, Daniel H. 2005. Proteomics in nutrition research: principles, technologies and applications. Br. J. Nutr. 94, 302-314. doi:10.1079/BJN20051458 PMid:16176599

Griffiths HR,Grant MM. 2006. The use of proteomic techniques to explore the holistic effects of nutrients in vivo. Nutr. Research. Rev. 19, 284-293. doi:10.1017/S0954422407249698

Hegsted DM, McGandy RB, Myers ML, Stare FJ. 1965. Quantitative effects of dietary fat on serum cholesterol in man. Am. J. Clin. Nutr. 17, 281-295.

Heid HW, Moll R, Schwetlick I, Rackwitz HR, Keenan TW. 1998. Adipophilin is a specific marker of lipid accumulation in diverse cell types and diseases. Cell Tissue Res. 294, 309-321. doi:10.1007/s004410051181 PMid:9799447

Hu FB, Willett WC. 2002. Optimal diets for prevention of coronary heart disease. JAMA 288, 2569-2578. doi:10.1001/jama.288.20.2569 PMid:12444864

Keys A, Anderson JT, Grande F. 1957. Prediction of serum-cholesterol responses of man to changes in fats in the diet. Lancet 273, 959-966. doi:10.1016/S0140-6736(57)91998-0

Keys A, Menotti A, Karvonen MJ, Aravanis C, Blackburn H, Buzina R, Djordjevic BS, Dontas AS, Fidanza F, Keys MH, . 1986. The diet and 15-year death rate in the seven countries study. Am. J. Epidemiol 124, 903-915.

Kim H, Page GP, Barnes S. 2004. Proteomics and mass spectrometry in nutrition research. Nutrition 20, 155-165. doi:10.1016/j.nut.2003.10.001 PMid:14698031

Krauss RM, Eckel RH, Howard B, Appel LJ, Daniels SR, Deckelbaum RJ, Erdman JW, Jr., Kris-Etherton P, Goldberg IJ, Kotchen TA, Lichtenstein AH, Mitch WE, Mullis R, Robinson K, Wylie-Rosett J, St Jeor S, Suttie J, Tribble DL, Bazzarre TL. 2000. AHA Dietary Guidelines: revision 2000: A statement for healthcare professionals from the Nutrition Committee of the American Heart Association. Circulation 102, 22842299.

Kritchevsky D, Tepper SA, Wright S, Tso P, Czarnecki SK. 2000. Influence of conjugated linoleic acid (CLA) on establishment and progression of atherosclerosis in rabbits. J. Am. Coll. Nutr. 19, 472S-477S.

Kussmann M, Raymond F, Affolter M. 2006. OMICSdriven biomarker discovery in nutrition and health. J. Biotechnol 124, 758-787. doi:10.1016/j.jbiotec.2006.02.014 PMid:16600411

Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. 2001. Initial sequencing and analysis of the human genome. Nature 409, 860-921. doi:10.1038/35057062 PMid:11237011

Lee KN, Kritchevsky D, Pariza MW. 1994. Conjugated linoleic acid and atherosclerosis in rabbits. Atherosclerosis 108, 19-25. doi:10.1016/0021-9150(94)90034-5 PMid:7980704

Livingston RJ, von Niederhausern A, Jegga AG, Crawford DC, Carlson CS, Rieder MJ, Gowrisankar S, Aronow BJ, Weiss RB, Nickerson DA. 2004. Pattern of sequence variation across 213 environmental response genes. Genome Res. 14, 1821-1831. doi:10.1101/gr.2730004 PMid:15364900 PMCid:524406

McLeod RS, LeBlanc AM, Langille MA, Mitchell PL, Currie DL. 2004. Conjugated linoleic acids, atherosclerosis, and hepatic very-low-density lipoprotein metabolism. Am. J. Clin. Nutr. 79, 1169S1174S.

McManaman JL, Zabaronick W, Schaack J, Orlicky DJ. 2003. Lipid droplet targeting domains of adipophilin. J. Lipid Res. 44, 668-673. doi:10.1194/jlr.C200021-JLR200

Mensink RP,Katan MB. 1992. Effect of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis of 27 trials. Arterioscler Thromb. 12, 911-919.

Milner JA. 2007. Nutrition in the ‘omics’ era. Forum Nutr. 60, 1-24. doi:10.1159/000107062 PMid:AMBIGUOUS 17684397,17210162

Nicolosi RJ, Rogers EJ, Kritchevsky D, Scimeca JA, Huth PJ. 1997. Dietary conjugated linoleic acid reduces plasma lipoproteins and early aortic atherosclerosis in hypercholesterolemic hamsters. Artery 22, 266-277.

Shimizu M, Tamamori-Adachi M, Arai H, Tabuchi N, Tanaka H, Sunamori M. 2002. Lipopolysaccharide pretreatment attenuates myocardial infarct size: A possible mechanism involving heat shock protein 70inhibitory kappaBalpha complex and attenuation of nuclear factor kappa B. J. Thorac. Cardiovasc. Surg. 124, 933-941. doi:10.1067/mtc.2002.122305 PMid:12407376

Toomey S, Roche H, Fitzgerald D, Belton O. 2003. Regression of pre-established atherosclerosis in the apoE-/- mouse by conjugated linoleic acid. Biochem . Soc. Trans. 31, 1075-1079.

van Vlijmen BJ, Mensink RP, ‘t Hof HB, Offermans RF, Hofker MH, Havekes LM. 1998. Effects of dietary fish oil on serum lipids and VLDL kinetics in hyperlipidemic apolipoprotein E*3-Leiden transgenic mice. J. Lipid Res. 39, 1181-1188.

van Vlijmen BJ, van ‘t Hof HB, Mol MJ, van der Boom H, van der Zee A, Frants RR, Hofker MH, Havekes LM. 1996. Modulation of very low density lipoprotein production and clearance contributes to age- and gender-dependent hyperlipoproteinemia in apolipoprotein E3-Leiden transgenic mice. J. Clin. Invest. 97, 1184-1192. doi:10.1172/JCI118532 PMid:8636429 PMCid:507170

van Vlijmen BJ, van den Maagdenberg AM, Gijbels MJ, van der Boom H, HogenEsch H, Frants RR, Hofker MH, Havekes LM. 1994. Diet -induced hyperlipoproteinemia and atherosclerosis in apolipoprotein E3-Leiden transgenic mice. J. Clin. Invest. 93, 1403-1410. doi:10.1172/JCI117117 PMid:8163645 PMCid:294153

Visioli F,Galli C. 2002. Biological properties of olive oil phytochemicals. Crit. Rev. Food Sci. Nutr. 42, 209-221. doi:10.1080/10408690290825529 PMid:12058980

Wilson TA, Nicolosi RJ, Chrysam M, Kritchevsky D. 2000. Conjugated linoleic acid reduces early aortic atherosclerosis greater than linoleic acid in hypercholesterolaemic hamsters. Nutr. Res. 20, 1795-1805. doi:10.1016/S0271-5317(00)00268-2

Zhang J, Sasaki S, Amano K, Kesteloot H. 1999. Fish consumption and mortality from all causes, ischemic heart disease, and stroke: an ecological study. Prev. Med. 28, 520-529. doi:10.1006/pmed.1998.0472 PMid:10329343

Zhu J, Quyyumi AA, Wu H, Csako G, Rott D, Zalles-Ganley A, Ogunmakinwa J, Halcox J, Epstein SE. 2003. Increased serum levels of heat shock protein 70 are associated with low risk of coronary artery disease. Arterioscler. Thromb. Vasc. Biol. 23, 1055-1059. doi:10.1161/01.ATV.0000074899.60898.FD




How to Cite

Rodríguez Gutiérrez G, de Roos B. Dietary fatty acids affecting hepatic metabolism and atherosclerosis – mechanisms unravelled using a proteomics approach. grasasaceites [Internet]. 2009Mar.30 [cited 2022Dec.7];60(1):28-32. Available from: