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Inflammatory serum proteome pattern in mice fed a high-fat diet

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Abstract

To investigate the influence of diet on serum protein pattern, mice were fed for 8 weeks either control chow or a high-fat diet (containing 21 % w/w milk fat and 0.2 % w/w cholesterol); sera were collected and analyzed by 2-DE. The main positive acute-phase reactant proteins, haptoglobin and hemopexin, were significantly up-regulated in animals receiving the high-fat diet. Data on all other proteins also pointed to an inflammatory condition in these animals. The largest change in concentration was observed for carboxylesterase N, a circulating enzyme seldom connected with lipid metabolism in earlier reports. These observations agree with the notion of a link between diet-induced hyperlipidemia and the inflammatory component of its cardiovascular sequels in humans, but the effects in the experimental animals are massive and obviously affect most of the major serum proteins.

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Abbreviations

apo:

Apolipoprotein

APR:

Acute-phase reactant (protein)

CRP:

C-reactive protein

h :

Human

KO:

Knock-out

m :

Mouse

MUP:

Major urinary protein-1

PPARα:

Peroxisome proliferator-activated receptor α

TG:

Transgenic

References

  • Aleksandrova K, Jenab M, Boeing H, Jansen E, de Bueno-Mesquita HB, Rinaldi S, Riboli E, Overvad K, Dahm CC, Olsen A, Tjonneland A, Boutron-Ruault MC, Clavel-Chapelon F, Morois S, Palli D, Krogh V, Tumino R, Vineis P, Panico S, Kaaks R, Rohrmann S, Trichopoulou A, Lagiou P, Trichopoulos D, van Duijnhoven FJ, Leufkens AM, Peeters PH, Rodriguez L, Bonet C, Sanchez MJ, Dorronsoro M, Navarro C, Barricarte A, Palmqvist R, Hallmans G, Khaw KT, Wareham N, Allen NE, Spencer E, Romaguera D, Norat T, Pischon T (2010) Circulating C-reactive protein concentrations and risks of colon and rectal cancer: a nested case-control study within the European prospective investigation into cancer and nutrition. Am J Epidemiol 172:407–418

    Article  PubMed  Google Scholar 

  • Athyros VG, Kakafika AI, Karagiannis A, Mikhailidis DP (2008) Do we need to consider inflammatory markers when we treat atherosclerotic disease? Atherosclerosis 200:1–12

    Article  PubMed  CAS  Google Scholar 

  • Bird RP, Mercer NJ, Draper HH (1985) Animal models for the study of nutrition and human disease: colon cancer, atherosclerosis, and osteoporosis. Adv Nutr Res 7:155–186

    Article  PubMed  CAS  Google Scholar 

  • Boin F, Rosen A (2007) Autoimmunity in systemic sclerosis: current concepts. Curr Rheumatol Rep 9:165–172

    Article  PubMed  CAS  Google Scholar 

  • Calpe-Berdiel L, Escola-Gil JC, Julve J, Zapico-Muniz E, Canals F, Blanco-Vaca F (2007) Differential intestinal mucosal protein expression in hypercholesterolemic mice fed a phytosterol-enriched diet. Proteomics 7:2659–2666

    Article  PubMed  CAS  Google Scholar 

  • Castellani LW, Weinreb A, Bodnar J, Goto AM, Doolittle M, Mehrabian M, Demant P, Lusis AJ (1998) Mapping a gene for combined hyperlipidaemia in a mutant mouse strain. Nat Genet 18:374–377

    Article  PubMed  CAS  Google Scholar 

  • Castro G, Nihoul LP, Dengremont C, de Geitere C, Delfly B, Tailleux A, Fievet C, Duverger N, Denefle P, Fruchart JC, Rubin EM (1997) Cholesterol efflux, lecithin-cholesterol acyltransferase activity, and pre-beta particle formation by serum from human apolipoprotein A-I and apolipoprotein A-I/apolipoprotein A-II transgenic mice consistent with the latter being less effective for reverse cholesterol transport. Biochemistry 36:2243–2249

    Article  PubMed  CAS  Google Scholar 

  • Cirillo P, Golino P, Calabro P, Cali G, Ragni M, De Rosa S, Cimmino G, Pacileo M, De Palma R, Forte L, Gargiulo A, Corigliano FG, Angri V, Spagnuolo R, Nitsch L, Chiariello M (2005) C-reactive protein induces tissue factor expression and promotes smooth muscle and endothelial cell proliferation. Cardiovasc Res 68:47–55

    Article  PubMed  CAS  Google Scholar 

  • Clement JG, Erhardt N (1990) Serum carboxylesterase activity in various strains of rats: sensitivity to inhibition by CBDP (2-/o-cresyl/4H:1:3:2-benzodioxaphosphorin-2-oxide). Arch Toxicol 64:414–416

    Article  PubMed  CAS  Google Scholar 

  • Cole BK, Keller SR, Wu R, Carter JD, Nadler JL, Nunemaker CS (2010) Valsartan protects pancreatic islets and adipose tissue from the inflammatory and metabolic consequences of a high-fat diet in mice. Hypertension 55:715–721

    Article  PubMed  CAS  Google Scholar 

  • Cray C, Zaias J, Altman NH (2009) Acute phase response in animals: a review. Comp Med 59:517–526

    PubMed  CAS  Google Scholar 

  • Daugherty A (2002) Mouse models of atherosclerosis. Am J Med Sci 323:3–10

    Article  PubMed  Google Scholar 

  • Daugherty A, Lu H, Howatt DA, Rateri DL (2009) Modes of defining atherosclerosis in mouse models: relative merits and evolving standards. Methods Mol Biol 573:1–15

    Article  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • Devaraj S, Singh U, Jialal I (2009) The evolving role of C-reactive protein in atherothrombosis. Clin Chem 55:229–238

    Article  PubMed  CAS  Google Scholar 

  • Djousse L, Gaziano JM (2009) Dietary cholesterol and coronary artery disease: a systematic review. Curr Atheroscler Rep 11:418–422

    Article  PubMed  CAS  Google Scholar 

  • Eberini I, Agnello D, Miller I, Villa P, Fratelli M, Ghezzi P, Gemeiner M, Chan JH, Aebersold R, Gianazza E (2000) Proteins of rat serum: V. Adjuvant arthritis and its modulation by non steroidal antiinflammatory drugs. Electrophoresis 21:2170–2179

    Article  Google Scholar 

  • Eisenhardt SU, Habersberger J, Peter K (2009) Monomeric C-reactive protein generation on activated platelets: the missing link between inflammation and atherothrombotic risk. Trends Cardiovasc Med 19:232–237

    Article  PubMed  CAS  Google Scholar 

  • El-Badri NS, Maheshwari A, Sanberg PR (2004) Mesenchymal stem cells in autoimmune disease. Stem Cells Dev 13:463–472

    Article  PubMed  Google Scholar 

  • Fazio S, Linton MF (2001) Mouse models of hyperlipidemia and atherosclerosis. Front Biosci 6:D515–D525

    Article  PubMed  CAS  Google Scholar 

  • Feng Y, Zhu Y, Chen X, Sha J, Fan L, Chen Q (2005) Effects of diet-induced hypercholesterolemia on testosterone-regulated protein expression in mice liver. J Nanosci Nanotechnol 5:1273–1276

    Article  PubMed  CAS  Google Scholar 

  • Genest J (2010) C-reactive protein: risk factor, biomarker and/or therapeutic target? Can J Cardiol 26(Suppl A):41A–44A

    Article  PubMed  CAS  Google Scholar 

  • Gianazza E (2009) Casting immobilized pH gradients. In: Walker JM (ed) The protein protocol handbook. Humana Press, Totowa, pp 305–322

    Chapter  Google Scholar 

  • Gianazza E, Giacon P, Sahlin B, Righetti PG (1985) Non-linear pH courses with immobilized pH gradients. Electrophoresis 6:53–56

    Article  CAS  Google Scholar 

  • Gianazza E, Eberini I, Villa P, Fratelli M, Pinna C, Wait R, Gemeiner M, Miller I (2002) Monitoring the effects of drug treatment in rat models of disease by serum protein analysis. J Chromatogr B 771:107–130

    Article  CAS  Google Scholar 

  • Gianazza E, Vegeto E, Eberini I, Sensi C, Miller I (2012a) Neglected markers: altered serum proteome in murine models of disease. Proteomics 12:691–707

    Google Scholar 

  • Gianazza E, Wait R, Eberini I, Sensi C, Sironi L, Miller I (2012b) Proteomics of rat biological fluids—the tenth anniversary update. J Proteomics 75:3113–3128

    Google Scholar 

  • Giugliano D, Ceriello A, Esposito K (2006) The effects of diet on inflammation: emphasis on the metabolic syndrome. J Am Coll Cardiol 48:677–685

    Article  PubMed  CAS  Google Scholar 

  • Haynes P, Miller I, Aebersold R, Gemeiner M, Eberini I, Lovati MR, Manzoni C, Vignati M, Gianazza E (1998) Proteins of rat serum: I. Establishing a reference 2-DE map by immunodetection and microbore high performance liquid chromatography-electrospray mass spectrometry. Electrophoresis 19:1484–1492

    Article  PubMed  CAS  Google Scholar 

  • Hortin GL, Sviridov D, Anderson NL (2008) High-abundance polypeptides of the human plasma proteome comprising the top 4 logs of polypeptide abundance. Clin Chem 54:1608–1616

    Article  PubMed  CAS  Google Scholar 

  • Hui X, Zhu W, Wang Y, Lam KS, Zhang J, Wu D, Kraegen EW, Li Y, Xu A (2009) Major urinary protein-1 increases energy expenditure and improves glucose intolerance through enhancing mitochondrial function in skeletal muscle of diabetic mice. J Biol Chem 284:14050–14057

    Article  PubMed  CAS  Google Scholar 

  • Igl W, Johansson A, Wilson JF, Wild SH, Polasek O, Hayward C, Vitart V, Hastie N, Rudan P, Gnewuch C, Schmitz G, Meitinger T, Pramstaller PP, Hicks AA, Oostra BA, van Duijn CM, Rudan I, Wright A, Campbell H, Gyllensten U (2010) Modeling of environmental effects in genome-wide association studies identifies SLC2A2 and HP as novel loci influencing serum cholesterol levels. PLoS Genet 6:e1000798

    Article  PubMed  Google Scholar 

  • Khovidhunkit W, Duchateau PN, Medzihradszky KF, Moser AH, Naya-Vigne J, Shigenaga JK, Kane JP, Grunfeld C, Feingold KR (2004) Apolipoproteins A-IV and A-V are acute phase proteins in mouse HDL. Atherosclerosis 176:37–44

    Article  PubMed  CAS  Google Scholar 

  • Kirpich IA, Gobejishvili LN, Bon Homme M, Waigel S, Cave M, Arteel G, Barve SS, McClain CJ, Deaciuc IV (2010) Integrated hepatic transcriptome and proteome analysis of mice with high-fat diet-induced nonalcoholic fatty liver disease. J Nutr Biochem 22:38–45

    Article  PubMed  Google Scholar 

  • Kisilevsky R, Tam SP, Ancsin JB (2008) The anti-atherogenic potential of serum amyloid A peptides. Curr Opin Investig Drugs 9:265–273

    PubMed  CAS  Google Scholar 

  • Koenig W, Khuseyinova N, Baumert J, Meisinger C (2008) Prospective study of high-sensitivity C-reactive protein as a determinant of mortality: results from the MONICA/KORA augsburg cohort study, 1984–1998. Clin Chem 54:335–342

    Article  PubMed  CAS  Google Scholar 

  • Kristiansson MH, Bhat VB, Babu IR, Wishnok JS, Tannenbaum SR (2007) Comparative time-dependent analysis of potential inflammation biomarkers in lymphoma-bearing SJL mice. J Proteome Res 6:1735–1744

    Article  PubMed  CAS  Google Scholar 

  • Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

    Article  PubMed  CAS  Google Scholar 

  • Lichtenstein AH, Kennedy E, Barrier P, Danford D, Ernst ND, Grundy SM, Leveille GA, Van Horn L, Williams CL, Booth SL (1998) Dietary fat consumption and health. Nutr Rev 56:S3–19 (discussion S19–S28)

    Article  PubMed  CAS  Google Scholar 

  • Lutgens E, Faber B, Schapira K, Evelo CT, van Haaften R, Heeneman S, Cleutjens KB, Bijnens AP, Beckers L, Porter JG, Mackay CR, Rennert P, Bailly V, Jarpe M, Dolinski B, Koteliansky V, de Fougerolles T, Daemen MJ (2005) Gene profiling in atherosclerosis reveals a key role for small inducible cytokines: validation using a novel monocyte chemoattractant protein monoclonal antibody. Circulation 111:3443–3452

    Article  PubMed  CAS  Google Scholar 

  • Miller I, Haynes P, Gemeiner M, Aebersold R, Manzoni C, Lovati MR, Vignati M, Eberini I, Gianazza E (1998) Proteins of rat serum: II. Influence of some biological parameters on the 2-DE pattern. Electrophoresis 19:1493–1500

    Article  PubMed  CAS  Google Scholar 

  • Miller I, Wait R, Sipos W, Gemeiner M (2009) A proteomic reference map for pig serum proteins as a prerequisite for diagnostic applications. Res Vet Sci 86:362–367

    Article  PubMed  CAS  Google Scholar 

  • Miller I, Eberini I, Gianazza E (2010) Other than IPG-DALT: 2-DE variants. Proteomics 10:586–610

    Article  PubMed  CAS  Google Scholar 

  • Nunemaker CS, Chen M, Pei H, Kimble SD, Keller SR, Carter JD, Yang Z, Smith KM, Wu R, Bevard MH, Garmey JC, Nadler JL (2008) 12-Lipoxygenase-knockout mice are resistant to inflammatory effects of obesity induced by Western diet. Am J Physiol Endocrinol Metab 295:E1065–E1075

    Article  PubMed  CAS  Google Scholar 

  • Okada S, List EO, Sankaran S, Kopchick JJ (2010) Plasma protein biomarkers correlated with the development of diet-induced type 2 diabetes in mice. Clin Proteomics 6:6–17

    Article  PubMed  CAS  Google Scholar 

  • Oswald J, Boxberger S, Jorgensen B, Feldmann S, Ehninger G, Bornhauser M, Werner C (2004) Mesenchymal stem cells can be differentiated into endothelial cells in vitro. Stem Cells 22:377–384

    Article  PubMed  Google Scholar 

  • Park JY, Seong JK, Paik YK (2004) Proteomic analysis of diet-induced hypercholesterolemic mice. Proteomics 4:514–523

    Article  PubMed  CAS  Google Scholar 

  • Passweg J, Tyndall A (2007) Autologous stem cell transplantation in autoimmune diseases. Semin Hematol 44:278–285

    Article  PubMed  Google Scholar 

  • Petro AE, Cotter J, Cooper DA, Peters JC, Surwit SJ, Surwit RS (2004) Fat, carbohydrate, and calories in the development of diabetes and obesity in the C57BL/6 J mouse. Metabolism 53:454–457

    Article  PubMed  CAS  Google Scholar 

  • Plump AS, Smith JD, Hayek T, Aalto-Setala K, Walsh A, Verstuyft JG, Rubin EM, Breslow JL (1992) Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell 71:343–353

    Article  PubMed  CAS  Google Scholar 

  • Puglisi MJ, Fernandez ML (2008) Modulation of C-reactive protein, tumor necrosis factor-alpha, and adiponectin by diet, exercise, and weight loss. J Nutr 138:2293–2296

    Article  PubMed  CAS  Google Scholar 

  • Ridker PM, Rifai N, Rose L, Buring JE, Cook NR (2002) Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. New Engl J Med 347:1557–1565

    Article  PubMed  CAS  Google Scholar 

  • Ross R (1999) Atherosclerosis: an inflammatory disease. New Engl J Med 340:115–126

    Article  PubMed  CAS  Google Scholar 

  • Sanders TA (2009) Fat and fatty acid intake and metabolic effects in the human body. Ann Nutr Metab 55:162–172

    Article  PubMed  CAS  Google Scholar 

  • Satoh T, Hosokawa M (1998) The mammalian carboxylesterases: from molecules to functions. Annu Rev Pharmacol Toxicol 38:257–288

    Article  PubMed  CAS  Google Scholar 

  • Schmid GM, Converset V, Walter N, Sennitt MV, Leung KY, Byers H, Ward M, Hochstrasser DF, Cawthorne MA, Sanchez JC (2004) Effect of high-fat diet on the expression of proteins in muscle, adipose tissues, and liver of C57BL/6 mice. Proteomics 4:2270–2282

    Article  PubMed  CAS  Google Scholar 

  • Schoonjans K, Staels B, Auwerx J (1996) The peroxisome proliferator activated receptors (PPARS) and their effects on lipid metabolism and adipocyte differentiation. Biochim Biophys Acta 1302:93–109

    Article  PubMed  CAS  Google Scholar 

  • Siri-Tarino PW, Sun Q, Hu FB, Krauss RM (2010) Saturated fat, carbohydrate, and cardiovascular disease. Am J Clin Nutr 91:502–509

    Article  PubMed  CAS  Google Scholar 

  • Sironi L, Gianazza E, Gelosa P, Guerrini U, Nobili E, Gianella A, Cremonesi B, Paoletti R, Tremoli E (2005) Rosuvastatin, but not simvastatin, provides end-organ protection in stroke-prone rats by antiinflammatory effects. Arterioscler Thromb Vasc Biol 25:598–603

    Article  PubMed  CAS  Google Scholar 

  • Tabibiazar R, Wagner RA, Deng A, Tsao PS, Quertermous T (2006) Proteomic profiles of serum inflammatory markers accurately predict atherosclerosis in mice. Physiol Genomics 25:194–202

    Article  PubMed  CAS  Google Scholar 

  • Temel RE, Rudel LL (2007) Diet effects on atherosclerosis in mice. Curr Drug Targets 8:1150–1160

    Article  PubMed  CAS  Google Scholar 

  • Van Greevenbroek MM, Vermeulen VM, De Bruin TW (2004) Identification of novel molecular candidates for fatty liver in the hyperlipidemic mouse model, HcB19. J Lipid Res 45:1148–1154

    Article  PubMed  Google Scholar 

  • Wait R, Miller I, Eberini I, Cairoli F, Veronesi C, Battocchio M, Gemeiner M, Gianazza E (2002) Strategies for proteomics with incompletely characterised genomes: the proteome of Bos taurus serum. Electrophoresis 23:3418–3427

    Article  PubMed  CAS  Google Scholar 

  • Wait R, Begum S, Brambilla D, Carabelli AM, Conserva F, Rocco Guerini A, Eberini I, Ballerio R, Gemeiner M, Miller I, Gianazza E (2005a) Redox options in two-dimensional electrophoresis. Amino Acids 28:239–272

    Article  PubMed  CAS  Google Scholar 

  • Wait R, Chiesa G, Parolini C, Miller I, Begum S, Brambilla D, Galluccio L, Ballerio R, Eberini I, Gianazza E (2005b) Reference maps of mouse serum acute phase proteins: changes with LPS-induced inflammation and apolipoprotein A-I and A-II transgenes. Proteomics 5:4245–4253

    Article  PubMed  CAS  Google Scholar 

  • Wan JB, Huang LL, Rong R, Tan R, Wang J, Kang JX (2010) Endogenously decreasing tissue n-6/n-3 fatty acid ratio reduces atherosclerotic lesions in apolipoprotein E-deficient mice by inhibiting systemic and vascular inflammation. Arterioscler Thromb Vasc Biol 30:2487–2494

    Article  PubMed  CAS  Google Scholar 

  • Zadelaar S, Kleemann R, Verschuren L, de Vries-Van der Weij J, van der Hoorn J, Princen HM, Kooistra T (2007) Mouse models for atherosclerosis and pharmaceutical modifiers. Arterioscler Thromb Vasc Biol 27:1706–1721

    Article  PubMed  CAS  Google Scholar 

  • Zhou Y, Jiang L, Rui L (2009) Identification of MUP1 as a regulator for glucose and lipid metabolism in mice. J Biol Chem 284:11152–11159

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This investigation was supported by grants from Fondazione Cariplo, Milano (MC) and from the European Commission SOUTH-LSHM-CT2006-037498 (MC).

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Correspondence to Elisabetta Gianazza.

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Gianazza, E., Sensi, C., Eberini, I. et al. Inflammatory serum proteome pattern in mice fed a high-fat diet. Amino Acids 44, 1001–1008 (2013). https://doi.org/10.1007/s00726-012-1433-5

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