Abstract
Previous investigations have demonstrated a marked effect of soy protein on multiple
physiological parameters associated with the metabolic syndrome (MS). This preliminary
study investigated the physiological effects of soy-based diets on cardiovascular
risk in a unique rodent model that reflects early stages of MS. Briefly, lean male
SHHF (+/cp) rats were randomly assigned to the following treatment groups: casein (control,
C); low-isoflavone (LIS) soy protein isolate; high-isoflavone (HIS) soy protein isolate;
or C+ 0.01 % rosiglitazone (CR). Rats were fed for thirty-six weeks. Liver weight,
heart weight, total plasma cholesterol, fasting blood glucose were lower in soy-fed
animals compared to control (p < 0.01). Body weight, kidney weight, alanine aminotransferase
(ALT), fasting plasma insulin, and homeostasis model assessment (HOMA) score were
also lower in LIS-fed rodents (p < 0.05) compared to casein treatment. All diet groups
exhibited lower urine protein (p < 0.01) and small arteriole content (p < 0.05) compared
to controls. LIS feed had a slightly more profound influence on body weight, liver
metabolism, and insulin sensitivity. However, both soy diets exhibited marked improvements
over a casein-based diet.
Key words
Soy protein - Rosiglitazone - Metabolic syndrome - Insulin - Cardiovascular disease
References
- 1
Cefalu W T.
Insulin resistance: cellular and clinical concepts.
Experimental Biology and Metabolism.
2001;
226
13-26
- 2
Reaven G M.
Pathophysiology of insulin resistance in human disease.
Physiological Reviews.
1995;
75
473-485
- 3
Grundy S M, Brewer H B Jr, Cleeman J I, Smith S C , Lenfant C, American Heart Association;
National Heart, Lung, and Blood Institute.
Definition of Metabolic Syndrome.
Circulation.
2004;
109
433-438
- 4
Reaven G, Abbasi F, McLaughlin T.
Obesity insulin resistance, and cardiovascular disease.
Recent Prog Horm Res.
2004;
59
207-223
- 5
Fonseca V.
Effect of Thiazolidinediones on body weight in patients with Diabetes Mellitus.
Am J Med.
2003;
115
42S-48S
- 6
Scheen A J.
Thiazolidinediones and liver toxicity.
Diabetes Metab..
2001;
27 (3)
305-313
- 7
Setchell K DR.
Phytoestrogens: the biochemistry, physiology, and implications for human health of
soy isoflavones.
Am J Clin Nutr.
1998;
68 (suppl)
1333S-1346S
- 8
Erdman J W, Fordyce E J.
Soy products and the human diet.
Am J Clin Nutr.
1989;
49
724-737
- 9
Potter S M, Baum J A, Teng H, Stillman R J, Shay N F, Erdman J W Jr.
Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal
woman.
Am J Clin Nutr.
1998;
68
1375S-1379S
- 10
Anderson J W, Johnstone B M, Cook-Newell M E.
Meta-analysis of the effects of soy protein intake on serum lipids.
N Eng J Med.
1995;
333
276-282
- 11
Baum J A, Teng H, Erdman J W, Weigel R M, Klein B P, Persky V W, Freels S, Surya P,
Bakhit R M, Ramos E, Shay N F, Potter S M.
Long-term intake of soy protein improves blood lipid profiles and increases mononuclear
cell low-density-lipoprotein receptor messenger RNA in hypercholesterolemic, postmenopausal
women.
Am J Clin Nutr.
1998;
68
545-551
- 12
Vahouny G V, Adamson I, Chalcarz W, Satchithanandam S, Muesing R, Klurfeld D M, Tepper S A,
Sanghvi A, Kritchevsky D.
Effects of casein and soy protein on hepatic and serum lipids and lipoprotein lipid
distribution in the rat.
Atherosclerosis.
1985;
56
127-137
- 13
Anthony M S, Clarkson T B, Williams K J.
Effects of soy isoflavones on atherosclerosis: potential mechanisms.
Am J Clin Nutr.
1998;
68
1390S-1393S
- 14
Anthony M S, Clarkson T B, Bullock B C, Wagner J D.
Soy protein versus soy phytoestrogens in the prevention of diet-induced coronary artery
atherosclerosis of male cynomolgus mokeys.
Atherosclerosis, Thrombosis, and Vascular Biology.
1997;
17
2524-2531
- 15
Maddox D A, Alavi F K, Silbernick E M, Zawada E T.
Protective effects of a soy diet in preventing obesity-linked renal disease.
Kidney International.
2002;
61
96-104
- 16
Peluso M R, Winters T A, Shanahan M F, Banz W J.
A cooperative interaction between soy protein and its isoflavone-enriched fraction
lowers hepatic lipids in male obese Zucker rats and reduces blood platelet sensitivity
in male Sprague-Dawley rats.
J Nutr.
2000;
130
2333-2342
- 17
Lavigne C, Marette A, Jacques H.
Cod and soy proteins compared with casein improve glucose tolerance and insulin sensitivity
in rats.
Endocrinology and Metabolism.
2000;
278
E491-E500
- 18
Iritani N, Sugimoto T, Fukuda H, Komiya M, Ikeda H.
Dietary soybean protein increases insulin receptor gene expression in Wistar Fatty
rats when dietary polyunsaturated fatty acid level is low.
J Nutr.
1997;
127
1077-1083
- 19
Tovar-Palacio C, Potter S M, Hafermann J C, Shay N F.
Intake of soy protein and soy protein extracts influencelipid metabolism and hepatic
gene expression in gerbils.
J Nutr.
1998;
128
839-842
- 20
Dixon R A, Ferreira D.
Genistein.
Phytochemistry.
2002;
60
205-211
- 21
Crouse J R 3rd, Morgan T, Terry J G, Ellis J, Vitolins M, Burke G L.
A randomized trial comparing the effect of casein with that of soy protein containing
varying amounts of isoflavones on plasma concentrations of lipids and lipoproteins.
Arch Intern Med.
1999;
159
2070-2076
- 22
Sanders T A, Dean T S, Grainger D, Miller G J, Wiseman H.
Moderate intakes of intact soy protein rich in isoflavones compared with ethanol-extracted
soy protein increase HDL but do not influence transforming growth factor β1 concentrations
and hemostatic risk factors for coronary heart disease in healthy subjects.
Am J Clin Nutr.
2002;
76
373-377
- 23
Fukui K, Tachibana N, Wanezaki S, Tsuzaki S, Takamatsu K, Yamamoto T, Hashimoto Y,
Shimoda T.
Isoflavone-free soy protein prepared by column chromatography reduces plasma cholesterol
in rats.
J Agric Food Chem.
2002;
50
5717-5721
- 24
Jenkins D J, Kendall C W, Jackson C J, Connelly P W, Parker T, Faulkner D, Vidgen E,
Cunnane S C, Leiter L A, Josse R G.
Effects of high- and low-isoflavone soyfoods on blood lipids, oxidized LDL, homocysteine,
and blood pressure in hyperlipidemic men and women.
Am J Clin Nutr.
2002;
76
365-372
- 25
Tofovic S P, Kusaka H, Kost C K Jr, Bastacky S.
Renal function and structure in diabetic, hypertensive, obese ZDFxSHHF-hybrid rats.
Ren Fail.
2000;
22 (4)
387-406
- 26
Hoversland R C.
Onset of obesity and puberty in genetically obese SHHF/Mcc-cp rats.
Int J Obes Relat Metab Disord.
1992;
16 (12)
977-984
- 27
Meier D A, Hennes M M, McCune S A, Kissebah A H.
Effects of obesity and gender on insulin receptor expression in liver of SHHF/Mcc-FAcp
rats.
Obes Res.
1995;
3 (5)
465-470
- 28
Reeves P G, Nielsen F H, Fahey G C Jr.
AIN-93 purified diets for laboratory rodents: final report of the American Institute
of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet.
J Nutr.
1993;
123
1939-1951
- 29
Maddox D A, Alavi F K, Santella R N, Zawada E T Jr.
Prevention of obesity-linked renal disease: age-dependent effects of dietary food
restriction.
Kidney Int.
2002;
62 (1)
208-219
- 30
Matthews D R, Hosker J P, Rudenski A S, Naylor B A, Treacher D F, Turner R C.
Homeostasis model assessment: insulin resistance and beta-cell function from fasting
plasma glucose and insulin concentrations in man.
Diabetologia.
1985;
28 (7)
412-419
- 31
Harris R B, Martin R J.
Specific depletion of body fat in parabiotic partners of tube-fed obese rats.
Am J Physiol.
1984;
247
R380-R386
- 32
Tomanek R J, Palmer P J, Peiffer G L, Schreiber K L, Eastham C L, Marcus M L.
Morphometry of canine coronary arteries, arterioles, and capillaries during hypertension
and left ventricular hypertrophy.
Circ Res.
1986;
58
38-46
- 33
Cimini C M, Weiss H R.
Microvascular morphometry and perfusion in renal hypertension-induced cardiac hypertrophy.
Am J Physiol.
1988;
255
H1384-H1390
- 34 Davis J, Higginbotham A, Iqbal J, Peterson R, Shay N, Banz W. Soy protein diets
attenuate abnormalities observed in male ZDF rats. 2003 Experimental Biology meeting
abstracts [accessed at http://select.biosis.org/faseb]. The FASEB Journal 18, Abstract
#197.2
- 35
Nagasawa A, Fukui K, Funahashi T, Maeda N, Shimomura I, Kihara S, Waki M, Takamatsu K,
Matsuzawa Y.
Effects of soy protein diet on the expression of adipose genes and plasma adiponectin.
Horm Metab Res.
2002;
34 (11 - 12)
635-639
- 36
Ishihara K, Oyaizu S, Fukuchi Y, Mizunoya W, Segawa K, Takahashi M, Mita Y, Fukuya Y,
Fushiki T, Yasumoto K.
A soybean peptide isolate diet promotes postprandial carbohydrate oxidation and energy
expenditure in type II diabetic mice.
J Nutr.
2003;
133 (3)
752-757
- 37
Saito M.
Effect of soy peptides on energy metabolism in obese animals [in Japanese].
Nutr. Sci. Soy Protein.
1991;
12
91-94
- 38
Anderson R, Wolf W.
Compositional changes in trypsin inhibitor, phytic acid, saponins, and isoflavones
related to soybean processing.
J Nutr.
1995;
125
581-588
- 39
Smith S A, Lister C A, Toseland C DN, Buckingham R E.
Rosiglitazone prevents the onset of hyperglycemia and proteinuria in the Zucker Diabetic
Fatty rat.
Diabetes, Obesity and Metabolism.
2000;
2
363-372
- 40
Brown K K, Henke B R, Blanchard S G, Cobb J E, Mook R, Kaldor I, Kliewer S A, Lehmann J M,
Lenhard J M, Harrington W W, Novak P J, Faison W, Binz J G, Hashim M A, Oliver W O,
Brown H R, Parks D J, Plunket K D, Tong W Q, Menius J A, Adkison K, Noble S A, Willson T M.
A novel n-aryl tyrosine activator of peroxisome proliferator-activated receptor-γ
reverses the diabetic phenotype of the Zucker Diabetic Fatty rat.
Diabetes.
1999;
48
1415-1424
- 41
Okuno A, Tamemoto H, Tobe K, Ueki K, Mori Y, Iwamoto K, Umesono K, Akanuma Y, Fujiwara T,
Horikoshi H, Yazaki Y, Kadowaki T.
Troglitazone increases the number of small adipocytes without the change of white
adipose tissue mass in obese Zucker rats.
J Clin Invest.
1998;
101
1354-1361
- 42
Vidal-Puig A, Jimenez-Linan M, Lowell B B, Hamann A, Hu E, Spiegelman B, Flier J S,
Moller D E.
Regulation of PPARγ gene expression by nutrition and obesity in rodents.
J Clin Invest.
1996;
97
2553-2561
- 43
Yakubu-Madus F E, Stephens T W, Johnson W T.
Lipid lowering explains the insulin sensitivity enhancing effects of a thizolidinedione,
5-(4-(2-(2-phenyl-4-oxazolyl)ethoxy)benzyl)-2,4 thiazolidinedione.
Diabetes, Obesity and Metabolism.
2000;
2
155-163
- 44
Smith U, Cogg S, Johansson A, Olausson T, Rotter V, Svalstedt B.
Thiazolidinediones (PPARγ agonists) but not PPAR α agonists increase IRS-2 gene expression
in 3T3-L1 and human adipocytes.
FASEB.
2001;
15
215-220
- 45
Zierath J R, Ryder J W, Doebber T, Woods J, Wu M, Ventre J, Li Z, McCrary C, Berger J,
Zhang B, Moller D E.
Role of skeletal muscle in thiazolidinedione insulin sensitizer (PPARγ agonist) action.
Endocrinology.
1998;
139
5034-5041
- 46
Berger J, Moller D E.
The mechanisms of action of PPARs.
Annu Rev Med.
2002;
53
409-435
- 47
Ricote M, Huang J T, Welch J S, Glass C K.
The peroxisome proliferators-activated receptor-γ (PPARγ) as a regulator of monocyte/macrophage
function.
J Leukoc Biol.
1999;
66
733-739
- 48
Keller J M, Collet P, Bianchi A, Huin C, Bouillaud-Kremarik P, Becuwe P, Schohn H,
Domenjoud L, Dauca M.
Implications of peroxisome proliferators-activatedreceptors (PPARS) in development,
cell life status, and disease.
Int J Dev Biol.
2000;
44
429-442
- 49
Willson T M, Lambert M H, Kilewer S A.
Peroxisome proliferator-activated receptor γ and metabolic disease.
Annu Rev Biochem.
2001;
70
341-367
- 50
Toruner F, Akbay E, Cakir N, Sancak B, Elbeg S, Taneri F, Akturk M, Karakoc A, Ayvaz G,
Arslan M.
Effects of PPARgamma and PPARalpha agonists on serum leptin levels in diet-induced
obese rats.
Horm Metab Res.
2004;
36 (4)
226-230
- 51
Mezei O, Banz W J, Steger R W, Peluso M R, Winters T A, Shay N.
Soy isoflavones exert antidiabetic and hypolipidemic effects through the PPAR pathways
in obese Zucker rats and murine RAW 264.7 cells.
J Nutr.
2003;
133
1238-1243
- 52
Jeong S K, Nam H S, Rhee J A, Shin J H, Kim J M, Cho K H.
Metabolic syndrome and ALT: a community study in adult Koreans.
Int J Obes Relat Metab Disord.
2004;
28 (8)
1033-1038
- 53
Hayashi U, Nagao K, Yshioka Y.
Relationship between food containing “Natto” (fermented soybeans) and the blood pressure
of SHR.
Jpn Heart.
J1976;
17
343-344
- 54
Nevala R, Vaskonen T, Vehniainen J, Korpela R, Vaatalo H.
Soy based diet attenuates the development of hypertension when compared with casein
based diet in spontaneously hypertensive rat.
Life Sci.
2000;
66
115-124
- 55
Martin D S, Breitkopf N P, Eyster K M, Williams J L.
Dietary soy exerts an antihypertensive effect in spontaneously hypertensive female
rats.
Am J Physiol Regul Integr Comp Physiol.
2001;
281 (2)
R553-R560
- 56
Anderson J W, Johnstone C M, Cook-Newell M E.
Meta-analysis of the effects of soy protein intake on serum lipids.
N Eng J Med.
1995;
333
276-282
- 57
Umeda M, Kanda T, Murakami M.
Effects of angiotensin II receptor antagonists on insulin resistance syndrome and
leptin in sucrose-fed spontaneously hypertensive rats.
Hypertens Res.
2003;
26 (6)
485-492
- 58
Smith S A, Lister C A, Toseland C D, Buckingham R E.
Rosiglitazone prevents the onset of hyperglycaemia and proteinuria in the Zucker diabetic
fatty rat.
Diabetes Obes Metab.
2000;
2 (6)
363-372
- 59
Schiffrin E L, Amiri F, Benkirane K, Iglarz M, Diep Q N.
Peroxisome proliferator-activated receptors: vascular and cardiac effects in hypertension.
Hypertension.
2003;
42 (4)
664-668
William J. Banz, Ph. D., RD
Department of Animal Science, Food and Nutrition, Southern Illinois University
Carbondale, IL 62901-4317, USA
Phone: +1 (618) 453-7511
Fax: +1 (618) 453-7517
Email: banz@siu.edu