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Experimental rat models to study the metabolic syndrome

  • Amaya Aleixandre de Artiñano (a1) and Marta Miguel Castro (a1) (a2)

Abstract

Being the metabolic syndrome a multifactorial condition, it is difficult to find adequate experimental models to study this pathology. The obese Zucker rats, which are homozygous for the fa allele, present abnormalities similar to those seen in human metabolic syndrome and are a widely extended model of insulin resistance. The usefulness of these rats as a model of non-insulin-dependent diabetes mellitus is nevertheless questionable, and they neither can be considered a clear experimental model of hypertension. Some experimental models different from the obese Zucker rats have also been used to study the metabolic syndrome. Some derive from the spontaneously hypertensive rats (SHR). In this context, the most important are the obese SHR, usually named Koletsky rats. Hyperinsulinism, associated with either normal or slightly elevated levels of blood glucose, is present in these animals, but SHR/N-corpulent rats are a more appropriated model of non-insulin-dependent diabetes mellitus. The SHR/NDmc corpulent rats, a subline of SHR/N-corpulent rats, also exhibit metabolic and histopathologic characteristics associated with human metabolic disorders. A new animal model of the metabolic syndrome, stroke-prone–SHR (SHRSP) fatty rats, was obtained by introducing a segment of the mutant leptin receptor gene from the Zucker line heterozygous for the fa gene mutation into the genetic background of the SHRSP. Very recently, it has been developed as a non-obese rat model with hypertension, fatty liver and characteristics of the metabolic syndrome by transgenic overexpression of a sterol-regulatory element-binding protein in the SHR rats. The Wistar Ottawa Karlsburg W rats are also a new strain that develops a nearly complete metabolic syndrome. Moreover, a new experimental model of low-capacity runner rats has also been developed with elevated blood pressure levels together with the other hallmarks of the metabolic syndrome.

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Corresponding author

*Corresponding author: Amaya Aleixandre de Artiñano, fax +34 91 3941463, email amaya@med.ucm.es

References

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1Burton-Freeman, B (2000) Dietary fiber and energy regulation. J Nutr 130, 272S275S.
2Zucker, LM & Zucker, TF (1961) Fatty, a new mutation in the rat. J Heredity 52, 275278.
3Chua, SC, Chung, WK, Wupeng, XS, et al. (1996) Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor. Science 271, 994996.
4Chua, SC Jr, White, DW, Wu-Peng, XS, et al. (1996) Phenotype of fatty due to Gln269Pro mutation in the leptin receptor (Lepr). Diabetes 45, 11411143.
5Phillips, MS, Liu, QY, Hammond, HA, et al. (1996) Leptin receptor missense mutation in the fatty Zucker rat. Nature Gen 13, 1819.
6Zhang, Y, Proenca, R, Maffei, M, et al. (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425432.
7Ahima, RS & Flier, JS (2000) Leptin. Annu Rev Physiol 62, 413437.
8Himms-Hagen, J (1999) Physiological roles of the leptin endocrine system; differences between mice and humans. Crit Rev Clin Lab Sci 36, 575655.
9Palou, A, Serra, F, Bonet, ML, et al. (2000) Obesity: molecular bases of a multifactorial problem. Eur J Nutr 39, 127144.
10Hardie, LJ, Rayner, DV, Holmes, S, et al. (1996) Circulating leptin levels are modulated by fasting, cold exposure and insulin administration in lean but not Zucker (fa/fa) rats as measured by ELISA. Biochem Biophys Res Commun 223, 660665.
11Picó, C, Sánchez, J, Oliver, P, et al. (2002) Leptin production by the stomach is up-regulated in obese (fa/fa) Zucker rats. Obesity Res 10, 932938.
12Beck, B (2000) Neuropeptides and obesity. Nutrition 16, 916923.
13Beck, B, Burlet, A, Nicolas, JP, et al. (1990) Hyperphagia in obesity is associated with a central peptidergic dysregulation in rats. J Nutr 120, 806811.
14Beck, B, Burlet, A, Nicolas, JP, et al. (1993) Galanin in the hypothalamus of fed and fasted lean and obese Zucker rats. Brain Res 623, 124130.
15Stricker-Krongrad, A, Dimitrov, T & Beck, B (2001) Central and peripheral dysregulation of melanin-concentrating hormone in obese Zucker rats. Brain Res Mol 92, 4348.
16Beck, B, Richy, S & Stricker-Krongrad, A (2004) Feeding response to ghrelin agonist and antagonist in lean and obese Zucker rats. Life Sci 76, 473478.
17Beck, B, Richy, S & Stricker-Krongrad, A (2003) Ghrelin and body weight regulation in the obese Zucker rat in relation to feeding state and dark/light cycle. Exp Biol Med 228, 11241131.
18Zucker, TF & Zucker, LM (1962) Hereditary obesity in the rat associated with high serum fat and cholesterol. Proc Soc Exp Biol Med 110, 165171.
19Zucker, TF & Zucker, LM (1963) Fat accretion and growth in the rat. J Nutr 80, 619.
20Zucker, LM & Antoniades, HN (1972) Insulin and obesity in the Zucker genetically obese rat ‘fatty’. Endocrinology 90, 13201330.
21Johnson, PR, Zucker, LM, Cruce, JA, et al. (1971) Cellularity of adipose depots in the genetically obese Zucker rat. J Lipid Res 12, 706714.
22Stern, J, Johnson, PR, Greenwood, MRC, et al. (1972) Insulin resistance and pancreatic insulin release in the genetically obese Zucker rat. Proc Soc Exp Biol Med 139, 6669.
23Bryce, GF, Johnson, PR, Sullivan, AC, et al. (1977) Insulin and glucagon: plasma levels and pancreatic release in the genetically obese Zucker rat. Horm Met Res 9, 366370.
24Ionescu, E, Sauter, JF & Jeanrenaud, B (1985) Abnormal glucose tolerance in genetically obese (fa/fa) rats. Am J Physiol 248, E500E506.
25Muller, S & Cleary, MP (1988) Glucose metabolism in isolated adipocytes from ad libitum- and restricted-fed lean and obese Zucker rats at two different ages. Proc Soc Exp Biol Med 187, 398407.
26Kasiske, BL, O'Donnell, MP & Keane, WF (1992) The Zucker rat model of obesity, insulin resistance, hyperlipidemia, and renal injury. Hypertension 19, I110I115.
27Stern, JS & Johnson, PR (1977) Spontaneous activity and adipose cellularity in the genetically obese Zucker rat (fafa). Metabolism 26, 371380.
28Vasselli, JR, Cleary, MP, Jen, KLC, et al. (1980) Development of food motivated behavior in free feeding and food restricted Zucker fatty (fa/fa) rats. Physiol Behav 25, 565573.
29Thornhill, JA, Taylor, B, Marshall, W, et al. (1982) Central, as well as peripheral naloxone administration suppresses feeding in food-deprived Sprague–Dawley and genetically obese (Zucker) rats. Physiol Behav 29, 841846.
30Grinker, JA, Drewnowski, A, Enns, M, et al. (1980) Effects of d-amphetamine and fenfluramine on feeding patterns and activity of obese and lean Zucker rats. Pharmacol Biochem Behav 12, 265275.
31Vasselli, JR, Haraczkiewicz, E, Maggio, CA, et al. (1983) Effects of a glucosidase inhibitor (acarbose, BAY g 5421) on the development of obesity and food motivated behavior in obese Zucker (fafa) rats. Pharmacol Biochem Behav 19, 8595.
32Maggio, CA, Haraczkiewicz, E & Vasselli, JR (1988) Diet composition alters the satiety effect of cholecystokinin in lean and obese Zucker rats. Physiol Behav 43, 485491.
33Cleary, MP, Vasselli, JR & Greenwood, MRC (1980) Development of obesity in Zucker obese (fafa) rat in absence of hyperphagia. Am J Physiol 238, E284E292.
34Hausman, DB, Fine, JB, Tagra, K, et al. (2003) Regional fat pad growth and cellularity in obese Zucker rats: modulation by caloric restriction. Obesity Res 11, 674682.
35Maggio, CA & Greenwood, MRC (1982) Adipose tissue lipoprotein lipase (LPL) and triglyceride uptake in Zucker rats. Physiol Behav 29, 11471152.
36Gruen, RK, Hietanen, E & Greenwood, MRC (1978) Increased adipose tissue lipoprotein lipase activity during the development of the genetically obese rat (fa/fa). Metabolism 27, 19551966.
37Turkenkopf, IJ, Olsen, JL, Moray, L, et al. (1980) Hepatic lipogenesis in the preobese Zucker rat. Proc Soc Exp Biol Med 164, 530533.
38Greenwood, MRC, Cleary, L & Steingrimsdottir, L (1981) Adipose tissue metabolism and genetic obesity: The LPL hypothesis. In Recent Advances in Obesity Research III, pp. 7579 [Bjorntorp, P, Cairella, M and Howard, AN, editors]. London: John Libbey.
39Greenwood, MRC (1985) Relationship of enzyme activity to feeding behavior in rats: lipoprotein lipase as the metabolic gatekeeper. Int J Obesity 9, 6770.
40Zucker, LM (1965) Hereditary obesity in the rat associated with hyperlipidemia. Ann N Y Acad Sci 131, 447458.
41Barry, WS & Bray, GA (1969) Plasma triglycerides in genetically obese rats. Metabolism 18, 833839.
42Schonfeld, G & Pfleger, B (1971) Overproduction of very low-density lipoproteins by livers of genetically obese rats. Am J Physiol 220, 11781181.
43Schonfeld, G, Felski, C & Howald, MA (1974) Characterization of the plasma lipoproteins of the genetically obese hyperlipoproteinemic Zucker fatty rat. J Lipid Res 15, 457464.
44Schirardin, H, Bach, A, Schaeffer, A, et al. (1979) Biological parameters of the blood in the genetically obese Zucker rat. Arch Intern Physiol Biochim 87, 275289.
45Witztum, JL & Schonfeld, G (1979) Lipoproteins in the plasma and hepatic perfusates of the Zucker fatty rat. Diabetes 28, 509516.
46Liao, W, Angelin, B & Rudling, M (1997) Lipoprotein metabolism in the fat Zucker rat: reduced basal expression but normal regulation of hepatic low density lipoprotein receptors. Endocrinology 138, 32763282.
47Vaskonen, T, Mervaala, E, Seppänen-Laakso, T, et al. (2001) Diet enrichment with calcium and magnesium enhances the cholesterol lowering effect of plant sterols in obese Zucker rats. Nutr Metab Cardiovasc Dis 11, 158167.
48Lin, RC (1985) Serum cholesterol, lecithin-cholesterol acyltransferase, and hepatic hydroxymethilglutaryl coenzyme A reductase activities of lean and obese Zucker rats. Metabolism 34, 1924.
49Lash, JM, Sherman, WM & Hamlin, RL (1989) Capillary basement membrane thickness and capillary density in sedentary and trained obese Zucker rats. Diabetes 38, 854860.
50Ernsberger, P & Nelson, DO (1988) Refeeding hypertension in dietary obesity. Am J Physiol 254, R47R55.
51Koletsky, S (1975) Pathologic findings and laboratory data in a new strain of obese hypertensive rats. Am J Pathol 80, 129140.
52Zemel, MB, Sowers, JR, Shehin, S, et al. (1990) Impaired calcium metabolism associated with hypertension in Zucker obese rats. Metabolism 39, 704708.
53Kurtz, TW, Morris, RC & Pershadsingh, HA (1989) The Zucker fatty rat as a genetic model of obesity and hypertension. Hypertension 13, 896901.
54Kasiske, BL, Cleary, MP, O'Donnell, MP, et al. (1985) Effects of genetic obesity on renal structure and function in the Zucker rat. J Lab Clin Med 106, 598604.
55Wu, X, Mäkynen, H, Kähönen, M, et al. (1996) Mesenteric arterial function in vitro in three models of experimental hypertension. J Hypertens 14, 365372.
56Yuen, VG, Pederson, RA, Dai, S, et al. (1996) Effects of low and high dose administration of bis(maltolato)oxovanadium(IV) on fa/fa Zucker rats. Can J Physiol Pharmacol 74, 10011009.
57Arvola, P, Wu, X, Kähönen, M, et al. (1999) Exercise enhances vasorelaxation in experimental obesity associated hypertension. Cardiovasc Res 43, 9921002.
58He, Y & MacLeod, KM (2002) Modulation of noradrenaline-induced vasoconstriction in isolated perfused mesenteric arterial beds from obese Zucker rats in the presence and absence of insulin. Can J Physiol Pharmacol 80, 171179.
59Zanchi, A, Delacrétaz, E, Taleb, V, et al. (1995) Endothelial function of the mesenteric arteriole and mechanical behaviour of the carotid artery in rats with insulin resistance and hypercholesterolaemia. J Hypertens 13, 14631470.
60Turner, NC & White, P (1996) Effects of streptozotocin-induced diabetes on vascular reactivity in genetically hyperinsulinaemic obese Zucker rats. J Cardiovasc Pharmacol 27, 884890.
61Alonso-Galicia, M, Brands, MW, Zappe, DH, et al. (1996) Hypertension in obese Zucker rats. Role of angiotensin II and adrenergic activity. Hypertension 28, 10471054.
62Kurtz, TW, Morris, RC & Pershadsingh, HA (1989) The Zucker fatty rat as a genetic model of obesity and hypertension. Hypertension 13, 896901.
63Subramanian, R & MacLeod, KM (2003) Age-dependent changes in blood pressure and arterial reactivity in obese Zucker rats. Eur J Pharmacol 477, 143152.
64Harte, A, McTernan, P, Chetty, R, et al. (2005) Insulin-mediated upregulation of the renin angiotensin system in human subcutaneous adipocytes is reduced by rosiglitazone. Circulation 111, 19541961.
65Rajagopalan, S, Kurz, S, Münzel, T, et al. (1996) Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. J Clin Invest 97, 19161923.
66Griendling, KK, Sorescu, D & Ushio-Fukai, M (2000) NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 86, 494501.
67Dzau, VJ (1988) Molecular and physiological aspects of tissue renin-angiotensin system: emphasis on cardiovascular control. J Hypertens Suppl 6, S7S12.
68Unger, T & Gohlke, P (1990) Tissue renin-angiotensin systems in the heart and vasculature: possible involvement in the cardiovascular actions of converting enzyme inhibitors. Am J Cardiol 65, 3I10I.
69De Gasparo, M (2002) AT(1) and AT(2) angiotensin II receptors: key features. Drugs 1, 110.
70Ouchi, N, Kihara, S, Funahashi, T, et al. (2003) Obesity, adiponectin and vascular inflammatory disease. Curr Opin Lipidol 14, 561566.
71Hotamisligil, GS, Shargill, NS & Spiegelman, BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259, 8791.
72Hotamisligil, GS, Arner, P, Caro, JF, et al. (1995) Increased adipose tissue expression of tumor necrosis-alpha in human obesity and insulin resistance. J Clin Invest 95, 24092415.
73Perreault, M & Marette, A (2001) Targeted disruption of inducible nitric oxide synthase protects against obesity-linked insulin resitance in muscle. Nat Med 7, 11381143.
74Wlodek, D & Gonzales, M (2003) Decreased energy levels can cause and sustain obesity. J Theor Biol 225, 3344.
75Boudina, S, Sena, S, O'Neill, BT, et al. (2005) Reduced mitochondrial oxidative capacity and increased mitochondrial uncoupling impair myocardial energetic in obesity-linked insulin resistance in muscle. Circulation 112, 26862695.
76Munzberg, H & Myers, MC (2005) Molecular and anatomical determinants of central leptin resistance. Nat Neurosci 8, 566570.
77Tilg, H & Moschen, AR (2006) Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6, 772773.
78Picchi, A, Gao, X, Belmadani, S, et al. (2006) Tumor necrosis factor-alpha induces endothelial dysfunction in the prediabetic metabolic syndrome. Circ Res 99, 6977.
79Reaven, GM, Chang, H, Hoffman, BB, et al. (1989) Resistance to insulin-stimulated glucose uptake in adipocytes isolated from spontaneously hypertensive rats. Diabetes 38, 11551160.
80Hulman, S, Falkner, B & Chen, YQ (1991) Insulin resistance in the spontaneously hypertensive rat. Metabolism 40, 359361.
81Aitman, TJ, Gotoda, T, Evans, AL, et al. (1997) Quantitative trait loci for cellular defects in glucose and fatty acid metabolism in hypertensive rats. Nat Genet 16, 197201.
82Aitman, TJ, Glazier, AM, Wallace, CA, et al. (1999) Identification of Cd36 (Fat) as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats. Nat Genet 21, 7683.
83Kvetnanský, R, Rusnák, M, Gasperíková, D, et al. (1997) Hyperinsulinemia and sympathoadrenal system activity in the rat. Ann N Y Acad Sci 827, 118134.
84Ishizuka, T, Ernsberger, P, Liu, S, et al. (1998) Phenotypic consequences of a nonsense mutation in the leptin receptor gene (fak) in obese spontaneously hypertensive Koletsky rats (SHROB). J Nutr 128, 22992306.
85Ernsberger, P, Ishizuka, T, Liu, S, et al. (1999) Mechanisms of antihyperglycemic effects of moxonidine in the obese spontaneously hypertensive Koletsky rat (SHROB). J Pharmacol Exp Ther 288, 139147.
86Koletsky, S (1973) Obese spontaneously hypertensive rats – a model for study of atherosclerosis. Exp Mol Pathol 19, 5360.
87Koletsky, S (1975) Pathologic findings and laboratory data in a new strain of obese hypertensive rats. Am J Pathol 80, 129142.
88Kastin, AJ, Pan, W, Maness, LM, et al. (1999) Decreased transport of leptin across the blood–brain barrier in rats lacking the short form of the leptin receptor. Peptides 20, 14491453.
89Koletsky, S (1975) Animal model: obese hypertensive rat. Am J Pathol 81, 463466.
90Michaelis, OE, Ellwood, KC, Judge, JM, et al. (1984) Effect of dietary sucrose on the SHR/N-corpulent rat: a new model for insulin-independent diabetes. Am J Clin Nutr 39, 612618.
91Michaelis, OE, Patrick, DH, Hansen, CT, et al. (1986) Insulin-independent diabetes mellitus (type II). Spontaneous hypertensive/NIH-corpulent rat. Am J Pathol 123, 398400.
92Michaelis, OE, Carswell, N, Velasquez, MT, et al. (1989) The role of obesity, hypertension and diet in diabetes and its complications in the Spontaneous Hypertensive/NIH-corpulent rat. Nutrition 5, 5659.
93Wexler, BC, Iams, SG & McMurtry, JP (1980) Pathophysiological differences between obese and non-obese spontaneously hypertensive rats. Br J Exp Pathol 61, 195207.
94Hiraoka, J, Hosoda, K, Ogawa, Y, et al. (1997) Augmentation of obese (ob) gene expression and leptin secretion in obese spontaneously hypertensive rats (obese SHR or Koletsky rats). Biochem Biophys Res Commun 231, 582585.
95Baly, DL, Zarnowski, MJ, Carswell, N, et al. (1989) Insulin resistant glucose transport activity in adipose cells from the SHR/N-corpulent rat. J Nutr 119, 628632.
96Striffler, JS, Bhathena, SJ, Michaelis, OE, et al. (1998) Long-term effects of perindopril on metabolic parameters and the heart in the spontaneously hypertensive/NIH-corpulent rat with non-insulin-dependent diabetes mellitus and hypertension. Metabolism 47, 11991204.
97Velasquez, MT, Kimmel, PL, Michaelis, OE 4th, et al. (1989) Effect of carbohydrate intake on kidney function and structure in SHR/N-cp rats. A new model of NIDDM. Diabetes 38, 679685.
98Triana, RJ, Suits, GW, Garrison, S, et al. (1991) Inner ear damage secondary to diabetes mellitus. I. Changes in adolescent SHR/N-cp rats. Arch Otolaryngol Head Neck Surg 117, 635640.
99Turley, SD & Hansen, CT (1986) Rates of sterol synthesis in the liver and extrahepatic tissues of the SHR/N-corpulent rat, an animal with hyperlipidemia and insulin-independent diabetes. J Lipid Res 27, 486496.
100Yamori, Y, Ohtaka, M, Horie, R, et al. (1978) Cerebral stroke and myocardial lesions in stroke-prone SHR. Jpn Heart J 19, 609611.
101Collins, HL, Rodenbaugh, DW & DiCarlo, SE (2000) Daily exercise attenuates the development of arterial blood pressure related cardiovascular risk factors in hypertensive rats. Clin Exp Hypertens 22, 193202.
102Hiraoka-Yamamoto, J, Nara, Y, Yasui, N, et al. (2004) Establishment of a new animal model of metabolic syndrome: SHRSP fatty (fa/fa) rats. Clin Exp Pharmacol Physiol 31, 107109.
103Marchesini, G, Brizi, M, Bianchi, G, et al. (2001) Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 50, 18441850.
104Marchesini, G, Bianchi, G, Merli, M, et al. (2003) Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial. Gastroenterology 124, 17921801.
105den Boer, M, Voshol, PJ, Kuipers, F, et al. (2004) Hepatic steatosis: a mediator of the metabolic syndrome. Lessons from animal models. Arterioscler Thromb Vasc Biol 24, 644649.
106Diehl, AM (2004) Tumor necrosis factor and its potential role in insulin resistance and nonalcoholic fatty liver disease. Clin Liver Dis 8, 619638.
107Qi, NR, Wang, J, Zidek, V, et al. (2005) A new transgenic rat model of hepatic steatosis and the metabolic syndrome. Hypertension 45, 10041011.
108Samuel, VT, Liu, ZX, Qu, X, et al. (2004) Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease. J Biol Chem 279, 32 34532 353.
109Horton, JD, Goldstein, JL & Brown, M (2002) SSREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 109, 11251131.
110Horton, JD, Goldstein, JL & Brown, M (2002) SSREBPs: transcriptional mediators of lipid homeostasis. Cold Spring Harb Symp Quant Biol 67, 491498.
111Horton, JD, Shimomura, I, Ikemoto, S, et al. (2003) Overexpression of sterol regulatory element-binding protein-1a in mouse adipose tissue produces adipocyte hypertrophy, increased fatty acid secretion, and fatty liver. J Biol Chem 278, 36 65236 660.
112Filippetti, R, Kloting, I, Massi, M, et al. (2007) Involvement of cocaine-amphetamine regulated transcript in the differential feeding responses to nociceptin/orphanin FQ in dark agouti and Wistar Ottawa Karlsburg W rats. Peptides 28, 19661973.
113van den Brandt, J, Kovács, P & Klöting, I (2000) Features of the metabolic syndrome in the spontaneously hypertriglyceridemic Wistar Ottawa Karlsburg W (RT1u Haplotype) rat. Metabolism 49, 11401144.
114van den Brandt, J, Kovács, P & Klöting, I (2000) Metabolic features in disease-resistant as well as in spontaneously hypertensive rats and newly established obese Wistar Ottawa Karlsburg inbred rats. Int J Obes Relat Metab Disord 24, 16181622.
115Klöting, I, Kovács, P & van den Brandt, J (2001) Sex-specific and sex-independent quantitative trait loci for facets of the metabolic syndrome in WOKW rats. Biochem Biophys Res Commun 284, 150156.
116Kovács, P, van den Brandt, J & Klöting, I (2000) Genetic dissection of the syndrome X in the rat. Biochem Biophys Res Commun 269, 660665.
117Klöting, I, Vogt, L & Serikawa, T (1995) Locus on chromosome 18 cosegregates with diabetes in the BB/OK rat subline. Diabete Metab 21, 338344.
118Grisk, O, Frauendorf, T, Schlüter, T, et al. (2007) Impaired coronary function in Wistar Ottawa Karlsburg W rats – a new model of the metabolic syndrome. Pflugers Arch 454, 10111021.
119Wisløff, U, Najjar, SM, Ellingsen, O, et al. (2005) Cardiovascular risk factors emerge after artificial selection for low aerobic capacity. Science 307, 418420.

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