The Journal of Nutritional Biochemistry
Volume 18, Issue 5 , Pages 313-321 , May 2007

Isoflavone-poor soy protein alters the lipid metabolism of rats by SREBP-mediated down-regulation of hepatic genes

Received 12 March 2006 ,Revised 22 May 2006 ,Accepted 25 May 2006.

References 

  1. Bakhit RM, Klein BP, Essex-Sorlie D, Ham JO, Erdman JW, Potter SM. Intake of 25 g soybean protein reduces plasma cholesterol in men with elevated cholesterol concentrations. J Nutr. 1994;124:213–222
  2. Anderson JW, Johnstone BM, Cook-Newell ME. Meta-analysis of the effects of soybean protein intake on serum lipids. N Engl J Med. 1995;333:276–282
  3. Sirtori CR, Lovati MR, Manzoni C, Gianazza E, Bondioli A, Staels B, et al. Reduction of serum cholesterol by soybean proteins: clinical experience and potential molecular mechanisms. Nutr Metab Cardiovasc Dis. 1998;8:334–340
  4. Tachibana N, Matsumoto I, Fukui K, Arai S, Kato H, Abe K, et al. Intake of soy protein isolate alters hepatic gene expression in rats. J Agric Food Chem. 2005;53:4253–4257
  5. Potter SM. Overview of proposed mechanisms for the hypocholesterolemic effect of soy. J Nutr. 1995;125:606S–611S
  6. Forsythe WA. Comparison of dietary casein or soy protein effects on plasma lipids and hormone concentrations in the gerbil (Meriones unguiculatus). J Nutr. 1986;116:1165–1171
  7. Greaves KA, Parks JS, Willians JK, Wagner JD. Intact dietary soy protein, but not adding an isoflavone-rich soy extract to casein, improves plasma lipids in ovariectomized cynomolgus monkeys. J Nutr. 1999;129:1585–1592
  8. Gardner CD, Newell KA, Cherin R, Haskell WL. The effect of soy protein with or without isoflavones relative to milk protein on plasma lipids in hypercholesterolemic postmenopausal women. Am J Clin Nutr. 2001;73:728–735
  9. Adams MR, Golden DL, Anthony MS, Register TC, Williams JK. The inhibitory effect of soy protein isolate on atherosclerosis in mice does not require the presence of LDL receptors or alteration of plasma lipoproteins. J Nutr. 2002;132:43–49
  10. Fukui K, Tachibana N, Wanezaki S, Tsuzaki S, Takamatsu K, Yamamoto T, et al. Isoflavone-free soy protein prepared by column chromatography reduces plasma cholesterol in rats. J Agric Food Chem. 2002;50:5717–5721
  11. Jenkins DJ, Kendall CW, Jackson JC, Connelly PW, Parker T, Faulkner D, et al. Effects of high- and low-isoflavones soyfoods on blood lipids, oxidized LDL, homocysteine, and blood pressure in hyperlipidemic men and women. Am J Clin Nutr. 2002;76:365–372
  12. Lichtenstein AH, Jalbert SM, Adlercreutz HZ, Goldin BR, Rasmussen H, Schaefer EJ, et al. Lipoprotein response to diets high in soy or animal protein with and without isoflavones in moderately hypercholesterolemic subjects. Arterioscler Thromb Vasc Biol. 2002;22:1852–1858
  13. Anthony MS, Clarkson TB, Bullock BC, Wagner JD. Soy protein versus soy phytooestrogens in the prevention on diet-induced coronary artery atherosclerosis of male cynomolgus monkeys. Arterioscler Thromb Vasc Biol. 1997;17:2524–2531
  14. Kirk EA, Sutherland P, Wang SA, Chait A, LeBoeuf RC. Dietary isoflavones reduce plasma cholesterol and atherosclerosis in C57BL/6 mice but not LDL receptor-deficient mice. J Nutr. 1998;128:954–959
  15. Sirtori CR, Galli G, Lovati MR, Carrara P, Bosisio E, Kienle MG. Effects of dietary proteins on the regulation of liver lipoprotein receptors in rats. J Nutr. 1984;114:1493–1502
  16. Lovati MR, Manzoni C, Canavesi A, Sirtori M, Vaccarino V, Marchi M, et al. Soybean protein diet increases low density lipoprotein receptor activity in mononuclear cells from hypercholesterolemic patients. J Clin Invest. 1987;80:1498–1502
  17. Lovati MR, Manzoni C, Agostinelli P, Ciappellano S, Mannucci L, Sirtori CR. Studies on the mechanism of the cholesterol lowering activity of soy proteins. Nutr Metab Cardiovasc Dis. 1991;1:18–24
  18. Lovati MR, Manzoni C, Gianazza E, Sirtori CR. Soybean protein products as regulators of liver low-density lipoprotein receptors: I. Identification of active β-conglycinin subunits. J Agric Food Chem. 1998;46:2474–2480
  19. Manzoni C, Lovati MR, Gianazza E, Sirtori CR. Soybean protein products as regulators of liver low-density lipoprotein receptors: II. α-α′ Rich commercial soy concentrate and α′ deficient mutant differently affect low-density lipoprotein receptor activation. J Agric Food Chem. 1998;46:2481–2484
  20. Lovati MR, Manzoni C, Gianazza E, Arnoldi A, Kuroswka E, Carroll KK, et al. Soy protein peptides regulate cholesterol homeostasis in Hep G2 cells. J Nutr. 2000;130:2543–2549
  21. Tovar AR, Murguía F, Cruz C, Hernández-Pando R, Aguilar-Salinas CA, Pedraza-Chaverri J, et al. A soy protein diet alters hepatic lipid metabolism gene expression and reduces serum lipids and renal fibrogenic cytokines in rats with chronic nephritic syndrome. J Nutr. 2002;132:2562–2569
  22. Nagasawa A, Fukui K, Kojima M, Kishida K, Maeda N, Nagaretani H, et al. Divergent effects of soy protein diet on the expression of adipocytokines. Biochem Biophys Res Commun. 2003;311:909–914
  23. Ascencio C, Torres N, Isoard-Acosta F, Gómez-Pérez FJ, Hernández-Pando R, Tovar AR. Soy protein affects serum insulin and hepatic SREBP-1 mRNA and reduces fatty liver in rats. J Nutr. 2004;134:522–529
  24. Liu K. Soybeans: chemistry, technology and utilization. Gaithersburg: Aspen; 1999;
  25. Vallett SM, Sanchez HB, Rosenfeld JM, Osborne TF. A direct role of sterol regulatory element binding protein in activation of 3-hydroxy-3-methylglutaryl coenzyme A reductase gene. J Biol Chem. 1996;271:12247–12253
  26. Horton JD, Goldstein JL, Brown MS. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest. 2002;109:1125–1131
  27. Nohturfft A, DeBose-Boyd RA, Scheek S, Goldstein JL, Brown MS. Sterols regulate cycling of SREBP cleavage-activating protein (SCAP) between endoplasmic reticulum and Golgi. Proc Natl Acad Sci U S A. 1999;96:11235–11240
  28. Nohturfft A, Yabe D, Goldstein JL, Brown MS, Espenshade PJ. Regulated step in cholesterol feedback localized to budding of SCAP from ER membranes. Cell. 2000;102:315–323
  29. Yabe D, Brown MS, Goldstein JL. Insig-2, a second endoplasmic reticulum protein that binds SCAP and blocks export of sterol regulatory element-binding proteins. Proc Natl Acad Sci U S A. 2002;99:12753–12758
  30. Yang T, Espenshade PJ, Wright ME, Yabe D, Gong Y, Aebersold R, et al. Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Cell. 2002;110:489–500
  31. Sever N, Song BL, Yabe D, Goldstein JL, Brown MS, DeBose-Boyd RA. Insig-dependent ubiquitination and degradation of mammalian 3-hydroxy-3-methylglutaryl-CoA reductase stimulated by sterols and geranylgeraniol. J Biol Chem. 2003;278:52479–52490
  32. Sever N, Yang T, Brown MS, Goldstein JL, DeBose-Boyd RA. Accelerated degradation of HMG-CoA reductase mediated by binding of insig-1 to its sterol-sensing domain. Mol Cell. 2003;11:25–33
  33. Shimano H, Yahagik N, Amemiya-Kudo M, Hasty AH, Osuga J, Tamura Y, et al. Sterol regulatory element-binding protein-1 as a key transcription factor for nutritional induction of lipogenic enzyme genes. J Biol Chem. 1999;274:35832–35839
  34. Shimomura I, Bashmakov Y, Ikemoto S, Horton JD, Brown MS, Goldstein JL. Insulin selectively increases SREBP-1c mRNA in the livers of rats with streptozotocin-induced diabetes. Mol Cell Biol. 1999;19:3760–3768
  35. Sugiyama K, Kanamori H, Akachi T, Yamakawa A. Amino acid composition of dietary proteins affects plasma cholesterol concentration through alteration of hepatic phospholipid metabolism in rats fed a cholesterol-free diet. J Nutr Biochem. 1996;7:40–48
  36. Morita T, Oh-Hashi A, Takei K, Ikai M, Ksaoka S, Kiriyama S. Cholesterol-lowering effects of soybean, potato and rice proteins depend on their low methionine contents in rat fed a cholesterol-free purified diet. J Nutr. 1997;127:470–477
  37. Sugiyama K, Yamakawa AA, Kumazawa A, Saeki S. Methionine content of dietary proteins affects the molecular species composition of plasma phosphatidylcholine in rats fed a cholesterol-free diet. J Nutr. 1997;127:600–607
  38. Gudbrandsen OA, Wergedahl H, Liaset B, Espe M, Berge RK. 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. 2005;94:321–330
  39. Reeves PG, Nielsen FH, Fahey GC. 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
  40. Fukui K, Tachibana N, Fukuda Y, Takamatsu K, Sugano M. Ethanol washing does not attenuate the hypocholesterolemic potential of soy protein. Nutrition. 2004;29:984–990
  41. Bilia AR, Salvini D, Mazzi G, Vincieri FF. Characterization of calendula flower, milk-thistle fruit, and passion flower tinctures by HPLC-DAD and HPLC-MS. Chromatographia. 2001;53:3–4
  42. Naumann C, Bassler R. Methodenbuch band: III. Die chemische Untersuchung von Futtermitteln. Darmstadt (Germany): VDLUFA-Verlag; 1993;
  43. Schuster R. Determination of amino acids in biological, pharmaceutical, plant and food samples by automated precolumn derivatization and high-performance liquid chromatography. J Chromatogr. 1988;431:271–284
  44. Sparks JD, Phung TL, Bolognino M, Cianci J, Khurana R, Peterson RG, et al. Lipoprotein alterations in 10- and 20-week-old Zucker diabetic fatty rats: hyperinsulinemic versus insulinopenic hyperglycemia. Metabolism. 1998;47:1315–1324
  45. Giudetti AM, Beynen AC, Lemmens AG, Gnoni GV, Geelen MJH. Hepatic fatty acid metabolism in rats fed diets with different contents of C18:0, C18:1 cis and C18:1 trans isomers. Br J Nutr. 2003;90:887–893
  46. Sirtori CR, Lovati MR, Manzoni C, Castiglioni S, Duranti M, Magni C, et al. Proteins of white lupin seed, a naturally isoflavone-poor legume, reduced cholesterolemia in rats and increase LDL receptor activity in HepG2 cells. J Nutr. 2004;134:18–23
  47. Hara A, Radin NS. Lipid extraction of tissues with a low toxicity solvent. Anal Biochem. 1978;90:420–426
  48. De Hoff JL, Davidson JH, Kritchevsky D. An enzymatic assay for determining free and total cholesterol in tissues. Clin Chem. 1978;24:433–435
  49. Hojnacki JL, Nicolosi RJ, Hayes KC. Densitometric quantitation of neutral lipids on ammonium sulfate impregnated thin-layer chromatograms. J Chromatogr. 1976;128:133–139
  50. Karpe F, Hamsten A. Determination of apolipoproteins B-48 and B-100 in triglyceride-rich lipoproteins by analytical SDS PAGE. J Lipid Res. 1994;35:1311–1317
  51. Brandsch C, Nass N, Eder K. A thermally oxidized dietary oil does not lower the activities of lipogenic enzymes in mammary glands of lactating rats but reduces the milk triglyceride concentration. J Nutr. 2004;134:631–636
  52. Mullen E, Brown RM, Osborne TF, Shay NF. Soy isoflavones affect sterol regulatory element binding proteins (SREBPs) and SREBP-regulated genes in HepG2 cells. J Nutr. 2004;134:2942–2947
  53. Tovar A, Manzano N, Torres N. Metabolism of cholesterol and fatty acids in nephrotic syndrome and its regulation by sterol regulatory element binding protein (SREBPs). Effect of soy protein consumption. Gac Med Mex. 2005;141:407–415
  54. Carroll KK, Kurowska EM. Soy consumption and cholesterol reduction: review of animal and human studies. J Nutr. 1995;125:587S–594S
  55. Meddings J, Spady D, Dietschy J. Kinetic constants for receptor-dependent and receptor-independent low density lipoprotein transport in the tissues of the rat and hamster. J Clin Invest. 1986;77:1474–1481
  56. Cianflone KM, Yasruel Z, Rodriguez MA, Vas D, Sniderman AD. Regulation of apoB secretion form HepG2 cells: evidence for a critical role for cholesteryl ester synthesis in the response to a fatty acid challenge. J Lipid Res. 1990;31:2045–2055
  57. Tanaka M, Jingami H, Otani H, Cho M, Ueda Y, Arai H, et al. Regulation of apolipoprotein B production and secretion in response to the change of intracellular cholesteryl ester contents in rabbit hepatocytes. J Biol Chem. 1993;268:12713–12718
  58. Ooyen C, Zecca A, Bersino AM, Catapano AL. NK-104, a potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, decreases apolipoprotein B-100 secretion from Hep G2 cells. Atherosclerosis. 1999;145:87–95
  59. Ali AA, Velasquez MT, Hansen CT, Mohamed AI, Bhathena SJ. Effects of soybean isoflavones, probiotics, and their interactions on lipid metabolism and endocrine system in an animal model of obesity and diabetes. J Nutr Biochem. 2004;15:583–590

PII: S0955-2863(06)00160-4

doi: 10.1016/j.jnutbio.2006.05.007

The Journal of Nutritional Biochemistry
Volume 18, Issue 5 , Pages 313-321 , May 2007