摘要
膳食蛋白不仅提供了人体必需的氨基酸，同时还包含了具有生物活性的多肽结构如：抗菌肽、降血压肽、抗氧化肽和降胆固醇肽等。占全世界谷物生产总量25%的稻米是亚洲许多国家的主要粮食作物。已有研究表明大米蛋白(white rice protein, WRP)具有降胆固醇作用，而有关大米蛋白酶解产物(white riceprotein hydrolysates, WRPH)、糙米蛋白(brown rice protein, BRP)及糙米蛋白酶解产物(brown rice proteinhydrolysates, BRPH)的降胆固醇作用却鲜有报道。
首先采用碱性蛋白酶Alcalase2.4L酶解WRP、BRP和大豆蛋白(soybean protein, SP)，研究了WRP、BRP、SP、WRPH、BRPH和大豆蛋白酶解产物(soybean protein hydrolysates, SPH)在胆固醇胶束溶液体系和Caco-2细胞中的降胆固醇活性以及在模拟胆汁酸溶液体系中对胆汁酸的束缚作用。结果表明三种蛋白质及其酶解产物都具有抑制胆固醇吸收和束缚胆汁酸的作用。
以喂食高脂高胆固醇饲料的雄性叙利亚金仓鼠为动物模型，以酪蛋白为对照，研究了WRP、BRP、SP及其酶解产物对动物脂质代谢的影响。结果表明，与酪蛋白相比，BRPH使仓鼠的最终体重和体重增加量分别显著(P <0.05)降低12%和76%，且仓鼠的最终体重与仓鼠粪便的干重、脂肪、甘油三酯及总氮含量呈显著(P <0.05)负相关关系，相关系数分别为-0.785、-0.871、-0.815和-0.795；WRPH、BRP、BRPH、SP和SPH可以显著(P <0.05)降低仓鼠血浆中的低密度脂蛋白(very low-density lipoproteincholesterol, VLDL-C)和肝脏中总胆固醇含量；WRPH、BRP、BRPH和SPH使仓鼠粪便中总脂肪含量显著(P <0.05)增加64%-280%；WRPH和BRPH分别使仓鼠粪便中的总胆固醇含量显著(P <0.05)增加206%和181%；WRP、WRPH、BRPH和SP还可以使仓鼠粪便中胆汁酸的含量显著(P <0.05)增加67%-75%。
利用实时定量PCR (real time PCR)研究了WRPH、BRP、BRPH和SPH对仓鼠肝脏中脂质代谢相关基因的表达。BRPH饲料组仓鼠肝脏中脂肪合成相关基因SCD1mRNA的表达量最低，而脂肪氧化相关基因PPARα、ACOX1和CPTI mRNA的表达量最高。在WRPH、BRP、BRPH和SPH饲料组中，CPTImRNA相对表达量与仓鼠最终体重和体重增加量呈负相关关系(r=-0.883, P=0.063和r=-0.775, P=0.1)；ACOX1mRNA相对表达量与仓鼠的最终体重呈负相关关系(r=-0.869, P=0.1)；CPTI mRNA相对表达量与仓鼠粪便中总脂肪含量呈显著正相关关系(r=0.946, P <0.05)；ACOX1mRNA相对表达量与仓鼠粪便总脂肪量呈显著负相关关系(r=-0.883, P <0.05)。WRPH、BRP、BRPH和SPH还可以增加胆固醇合成相关基因CYP51和胆汁酸合成相关基因CYP7A1mRNA表达量。在BRPH饲料组中，CYP51mRNA的表达量与仓鼠肝脏中总胆固醇含量呈负相关关系(r=-0.969, P <0.05)，而与仓鼠粪便中胆固醇排出量呈正相关关系(r=0.758, P=0.1)。
以喂食高脂高胆固醇饲料的小鼠为动物模型，研究了大豆蛋白来源的，具有体外降低胆固醇活性的多肽LPYPR和WGAPSI对小鼠脂质代谢的调节作用。多肽可以降低血浆中VLDL-C和甘油三酯含量，但是随着多肽含量的增加，小鼠血浆中总胆固醇含量却在增加。同时，多肽还可以降低小鼠粪便中的胆汁酸含量。除WGAPSI0.45g/kg diet (W0.45)饲料组外，其他多肽饲料组可以增加小鼠肝脏中CYP51、LDLR和CYP7A1mRNA水平。
Dietary protein is not only the source of essential amino acids required for growth or maintenance but alsocontains amino acid sequences for peptides that have antimicrobial, blood pressure-lowering (ACE inhibitor),anti-oxidative, and cholesterol-lowering properties. Rice (Oryza sativa) accounting for about25%of the worldcereal grain production is the staple food in most Asian countries. White rice protein (WRP) has been shown tohave hypocholesterolemic properties in several studies, but to our knowledge the hypocholesterolemic ability ofwhite rice protein hydrolysates (WRPH), brown rice protein (BRP), and brown rice protein hydrolysates (BRPH)has not been reported.
WRP, BRP, and soybean protein (SP) were hydrolyzed by peptidases Alcalase2.4L. The cholesterollowering ability of WRP, BRP, SP, WRPH, BRPH, and soybean protein hydrolysates (SPH) was identified usingcholesterol micellar solution and Caco-2cell and their bile acid binding ability was indentified using artificial bileacid solution. The results showed all original proteins and their hydrolysates had cholesterol-lowering and bileacid binding abilities.
The effects on lipid metabolism of WRP, BRP, SP, and their hydrolysates were studied using Male SyrianGolden hamsters fed high-fat and-cholesterol diets. Compared with casein, the final body weight and weight gainwere significantly (P <0.05) reduced12%and76%in BRPH diet group. Fecal dry weight, lipid, triglyceride andnitrogen contents were negatively correlated, r=-0.785, r=-0.871, and r=-0.795, respectively, with final bodyweight (P <0.05). In WRPH, BRP, BRPH, SP, and SPH diet groups, the plasma very low-density lipoproteincholesterol (VLDL-C) and hepatic total cholesterol contents were significantly (P <0.05) lower compared withthe control group. WRPH, BRP, BRPH, and SPH significantly (P <0.05) increased the fecal total lipid content(64%-280%) compared with casein. Compared with the control group, WRPH and BRPH significantly (P <0.05)increased the fecal total cholesterol excretion (206%and108%) and WRP, WRPH, BRPH, and SP significantly(P <0.05) increased the fecal total bile acid excretion (67%-75%).
Hamsters fed the BRPH supplemented diet had the lowest mRNA level of lipid biosynthesis gene SCD1andhighest mRNA levels of lipid oxidation gene, PPARα, ACOX1, and CPTI. In WRPH, BRP, BRPH, and SPH dietgroups, there were negative correlations between mRNA level of CPTI and final body weight (r=-0.883, P=0.063) and body weight gain (r=-0.775, P=0.1). The negative correlation was also observed between mRNAlevel of ACOX1and final body weight (r=-0.869, P=0.1). Correlations between fecal total lipid concentrationand mRNA levels of CPTI (r=0.946, P <0.05) and ACOX1(r=-0.883, P <0.05) were observed. The mRNAlevels of CYP51and CYP7A1were up-regulated in WRPH, BRP, BRPH, and SPH. In the BRPH diet group,hepatic and fecal total cholesterol concentrations were negatively (r=-0.969, P <0.05) and positively (r=0.758,P=0.1) correlated, respectively, with the expression of CYP51.
The effects on lipid metabolism of soybean protein peptides LPYPR and WGAPSI, with micellar cholesterolinhibition ability in vitro were identified using mice fed high-fat and-cholesterol diets. Except the reduction ofVLDL-C and triglyceride concentrations, the peptides containing diets increased the plasma cholesterolconcentration with increasing dose of the peptides. Mice fed diets supplemented with the peptides also had lowerfecal bile acid excretion. The mRNA levels of the genes CYP51, LDLR, and CYP7A1were up regulated in micefed diets supplemented with peptides except the WGAPSI (0.45g/kg diet) diet group.
引文
1Durrington PN. Hyperlipidaemia: Diagnosis and management. London: Butterworth-Heinemann,1995.27-37.
2Harrison TR, Fauci AS. Harrison's principles of internal medicine. New York: McGraw-Hill, Health Professio-ns Division,1998.
3Robert K. Murray, David A Bender, Kathleen M. Botham et al. Harper's illustrated biochemistry. The McGraw-Hill Companies, Inc.,2009.430-470.
4Davis RA, Attie AD, Deletion of the ileal basolateral bile acid transporter identifies the cellular sentinels thatregulate the bile acid pool. PNAS,2008,105(13):4965-4966.
5Li T, Matozel M, Boehme S et al, Overexpression of cholesterol7α-hydroxylase promotes hepatic bile acidsynthesis and secretion and maintains cholesterol homeostasis. Hepatology,2011,53(3):996-1006.
6Chiang JYL, Bile acids: Regulation of synthesis. J Lipid Res,2009,50(10):1955-1966.
7Reshef L, Olswang Y, Cassuto H et al, Glyceroneogenesis and the triglyceride/fatty acid cycle. J Biol Chem,2003,278(33):30413-30416.
8Coleman RA, Lee DP, Enzymes of triacylglycerol synthesis and their regulation. Prog Lipid Res,2004,43(2):134-176.
9Coleman RA, Lewin TM, Muoio DM. Physiological and nutritional regulation of enzymes of triacylglycerolsynthesis. Annu Rev Nutr,2000,20:77–103.
10Wu X, Shang A, Jiang H et al, Low rates of apob secretion from hepg2cells result from reduced delivery ofnewly synthesized triglyceride to a "Secretion-coupled" Pool. J Lipid Res,1996,37(6):1198-1206.
11Jahan-Mihan A, Luhovyy BL, Khoury DE et al, Dietary proteins as determinants of metabolic and physiologicfunctions of the gastrointestinal tract. Nutrients,2011,3(5):574-603.
12Zaloga GP, Siddiqui RA, Biologically active dietary peptides. Mini Rev Med Chem,2004,4(8):815-821.
13Tripathy K, Lotero, Bolanos O, Role of dietary protein upon serum cholesterol level in malnourished subjects.Am J Clin Nutr,1970,23(9):1160-1168.
14Carroll KK, Hypercholesterolemia and atherosclerosis: Effects of dietary protein. Fed Proc,1982,41(11):2792-2796.
15Nagaoka S, Futamura Y, Miwa K et al, Identification of novel hypocholesterolemic peptides derived frombovine milk [beta]-lactoglobulin. Biochem Biophys Res Commun,2001,281(1):11-17.
16Asato L, Wang MF, Chan YC et al, Effect of egg white on serum cholesterol concentration in young women. JNutr Sci Vitaminol (Tokyo),1996,42(2):87-96.
17Nagaoka S, Masaoka M, Zhang Q et al, Egg ovomucin attenuates hypercholesterolemia in rats and inhibitscholesterol absorption in caco-2cells. Lipids,2002,37(3):267-272.
18Holmes WL, Rubel GB, Hood SS, Comparison of the effect of dietary meat versus dietary soybean protein onplasma lipids of hyperlipidemic individuals. Atherosclerosis,1980,36(3):379-387.
19Jacques H, Deshaies Y, Savoie L, Relationship between dietary proteins, their in vitro digestion products, andserum cholesterol in rats. Atherosclerosis,1986,61(2):89-98.
20Hosomi R, Fukunaga K, Arai H et al, Fish protein decreases serum cholesterol in rats by inhibition of cholest-erol and bile acid absorption. J Food Sci,2011,76(4):H116-H121.
21Morimatsu F, Ito M, Budijanto S et al, Plasma cholesterol-suppressing effect of papain-hydrolyzed pork meatin rats fed hypercholesterolemic diet. J Nutr Sci Vitaminol (Tokyo),1996,42(2):145-153.
22Lefevre M, Schneeman BO, High density lipoprotein composition in rats fed casein or soybean protein isolate.J Nutr,1984,114(4):768-777.
23Khosla P, Samman S, Carroll KK, Decreased receptor-mediated ldl catabolism in casein-fed rabbits precedesthe increase in plasma cholesterol levels. J Nutr Biochem,1991,2(4):203-209.
24Sirtori CR, Lovati MR, Manzoni C et al, Soy and cholesterol reduction: Clinical experience. J Nutr,1995,125(3Suppl):598S-605S.
25Cohn JS, Kimpton WG, Nestel PJ, The effect of dietary casein and soybean protein on cholesterol and verylow density lipoprotein metabolism in the rat. Atherosclerosis,1984,52(2):219-231.
26Kurowska EM, Hrabek-Smith JM, Carroll KK, Compositional changes in serum lipoproteins duringdeveloping hypercholesterolemia induced in rabbits by cholesterol-free, semipurified diets. Atherosclerosis,1989,78(2-3):159-165.
27Frota KMG, Mendon a S, Saldiva PHN et al, Cholesterol-lowering properties of whole cowpea seed and itsprotein isolate in hamsters. J Food Sci,2008,73(9):H235-H240.
28Jacques H, Gascon A, Bergeron N et al, Role of dietary fish protein in the regulation of plasma lipids. Can JCardiol,1995,11Suppl G:63G-71G.
29Bydlowski SP, Stivaletti VL, Douglas CR, Biochemical observations on rat aortas: Effect of protein refeedingafter a protein depletion period. Ann Nutr Metab,1984,28(2):85-91.
30Bydlowski SP, Stivaletti VL, Douglas CR, Biochemical observations on rat aorta: Interaction of dietary protei-n and cholesterol. Br J Nutr,1986,55(2):295-304.
31Lovati MR, West CE, Sirtori CR et al, Dietary animal proteins and cholesterol metabolism in rabbits. Br JNutr,1990,64(2):473-485.
32Newburgh LH, Clarkson S, Production of arteriosclerosis in rabbits by diets rich in animal proteins. J AMA,1922,79(14):1106-1108.
33Hamilton RM, Carroll KK, Plasma cholesterol levels in rabbits fed low fat, low cholesterol diets: Effects ofdietary proteins, carbohydrates and fibre from different sources. Atherosclerosis,1976,24(1-2):47-62.
34Jones RJ, Huffman S, Chronic effect of dietary protein on hypercholesteremia in the rat. Proceedings of theSociety for Experimental Biology and Medicine Society for Experimental Biology and Medicine (New York, NY),1956,93(3):519-522.
35Leclerc J, Chanussot B, Miller ML et al, Effects of protein level, methionine supplementation andcarbohydrate type of the diet on liver lipid and plasma free threonine contents in the lactating rat. Reprod NutrDev,1989,29(3):269-276.
36Grundy SM, Absorption and metabolism of dietary cholesterol. Annu Rev Nutr,1983,3:71-96.
37Huff MW, Carroll KK, Effects of dietary protein on turnover, oxidation, and absorption of cholesterol, and onsteroid excretion in rabbits. J Lipid Res,1980,21(5):546-548.
38Nagata Y, Ishiwaki N, Sugano M, Studies on the mechanism of antihypercholesterolemic action of soybeanprotein and soybean protein-type amino acid mixtures in relation to the casein counterparts in rats. J Nutr,1982,112(8):1614-1625.
39Tanaka K, Imaizumi K, Sugano M, Effects of dietary proteins on the intestinal synthesis and transport ofcholesterol and apolipoprotein a-i in rats. J Nutr,1983,113(7):1388-1394.
40Wergedahl H, Liaset B, Gudbrandsen OA et al, Fish protein hydrolysate reduces plasma total cholesterol,increases the proportion of hdl cholesterol, and lowers acyl-coa:Cholesterol acyltransferase activity in liver ofzucker rats. J Nutr,2004,134(6):1320-1327.
41Megías C, Pedroche J, Del Mar Yust M et al, Sunflower protein hydrolysates reduce cholesterol micellarsolubility. Plant Foods Hum Nutr,2009,64(2):86-93.
42Lin YH, Tsai JS, Hung LB et al, Hypocholesterolemic effect of compounded freshwater clam proteinhydrolysate and gracilaria. Food Chem,2010,123(2):395-399.
43Yoshie-Stark Y, W sche A, In vitro binding of bile acids by lupin protein isolates and their hydrolysates. FoodChem,2004,88(2):179-184.
44Beynen A, West C, Cholesterol metabolism in swine fed diets containing either casein or soybean protein. JAm Oil Chem Soc,1987,64(8):1178-1182.
45Lapre JA, West CE, Lovati MR et al, Dietary animal proteins and cholesterol metabolism in rats. Int J VitamNutr Res,1989,59(1):93-100.
46Kuyvenhoven MW, West CE, Van Der Meer R et al, Fecal steroid excretion in relation to the development ofcasein-induced hypercholesterolemia in rabbits. J Nutr,1986,116(8):1395-1404.
47McClelland JW, Shih JCH, Prevention of hypercholesterolemia and atherosclerosis in japanese quail by highintake of soybean protein. Atherosclerosis,1988,74(1-2):127-138.
48Ozben T, Biliary lipid composition and gallstone formation in rabbits fed on soybean protein, cholesterol,casein and modified casein. Biochem J,1989,263(1):293-296.
49Vahouny GV, Adamson I, Chalcarz W et al, Effects of casein and soybean protein on hepatic and serum lipidsand lipoprotein lipid distributions in the rat. Atherosclerosis,1985,56(2):127-137.
50Shukla A, Brandsch C, Bettzieche A et al, Isoflavone-poor soybean protein alters the lipid metabolism of ratsby srebp-mediated down-regulation of hepatic genes. J Nutr Biochem,2007,18(5):313-321.
51Iritani N, Nagashima K, Fukuda H et al, Effects of dietary proteins on lipogenic enzymes in rat liver. J Nutr,1986,116(2):190-197.
52Iritani N, Hosomi H, Fukuda H et al, Soybean protein suppresses hepatic lipogenic enzyme gene expression inwistar fatty rats. J Nutr,1996,126(2):380-388.
53Moriyama T, Kishimoto K, Nagai K et al, Soybean beta-conglycinin diet suppresses serum triglyceride levelsin normal and genetically obese mice by induction of beta-oxidation, downregulation of fatty acid synthase, andinhibition of triglyceride absorption. Biosci Biotechnol Biochem,2004,68(2):352-359.
54Demonty I, Deshaies Y, Lamarche B et al, Cod protein lowers the hepatic triglyceride secretion rate in rats. JNutr,2003,133(5):1398-1402.
55Mathew BC, Daniel RS, Augusti KT, Hypolipidemic effect of garlic protein substituted for casein in diet ofrats compared to those of garlic oil. Indian J Exp Biol,1996,34(4):337-340.
56Giroux I, Kurowska EM, Carroll KK, Role of dietary lysine, methionine, and arginine in the regulation ofhypercholesterolemia in rabbits. J Nutr Biochem,1999,10(3):166-171.
57Regina M, Korhonen VP, Smith TK et al, Methionine toxicity in the rat in relation to hepatic accumulation ofs-adenosylmethionine: Prevention by dietary stimulation of the hepatic transsulfuration pathway. Arch BiochemBiophys,1993,300(2):598-607.
58Sugiyama K, Kanamori H, Akachi T et al, Amino acid composition of dietary proteins affects plasmacholesterol concentration through alteration of hepatic phospholipid metabolism in rats fed a cholesterol-free diet.J Nutr Biochem,1996,7(1):40-48.
59Ghosh P, Misra UK, Rice diet deficient in lysine and threonine alters normal cholesterol metabolism of rathepatic golgi apparatus. Nutr Res,1987,7(6):637-643.
60Morita T, Oh-hashi A, Takei K et al, Cholesterol-lowering effects of soybean, potato and rice proteins dependon their low methionine contents in rats fed a cholesterol-free purified diet. J Nutr,1997,127(3):470-477.
61McGregor D, The effects of some dietary changes upon the concentrations of serum lpids in rats. Br J Nutr,1971,25(2):213-224.
62Bassat M, Mokady S, The effect of amino-acid-supplemented wheat gluten on cholesterol metabolism in therat. Br J Nutr,1985,53(1):25-30.
63Mokady S, Einav P, Effect of dietary wheat gluten in lipid metabolism in growing rats. Nutr Metab,1978,22(3):181-189.
64Mokady S, Liener IE, Effect of plant proteins on cholesterol metabolism in growing rats fed atherogenic diets.Ann Nutr Metab,1982,26(2):138-144.
65Iwami K, Sakakibara K, Ibuki F, Involvement of post-digestion\'\'hydrophobia\'\'peptides in plasma cholester-ol-lowering effect of dietary plant proteins. Agric Biol Chem,1986,50(5):1217-1222.
66Alladi S, Shanmugasundaram KR, Induction of hypercholesterolemia by supplementing soybean protein withacetate generating amino acids. Nutr Rep Int1989,40:893–900.
67Kurowska EM, Carroll KK, Essential amino acids in relation to hypercholesterolemia induced in rabbits bydietary casein. J Nutr,1990,120(8):831-836.
68Huff MW, Carroll KK, Effects of dietary proteins and amino acid mixtures on plasma cholesterol levels inrabbits. J Nutr,1980,110(8):1676-1685.
69Carroll KK, Kurowska EM, Soy consumption and cholesterol reduction: Review of animal and human studies.J Nutr,1995,125(3Suppl):594S-597S.
70Gardner ML, Absorption of amino acids and peptides from a complex mixture in the isolated small intestine ofthe rat. J Physiol,1975,253(1):233-256.
71Webb KE, Matthews JC, DiRienzo DB, Peptide absorption: A review of current concepts and futureperspectives. J Anim Sci,1992,70(10):3248-3257.
72De Schrijver R, Cholesterol metabolism in mature and immature rats fed animal and plant protein. J Nutr,1990,120(12):1624-1632.
73Woodward CJ, Carroll KK, Digestibilities of casein and soya-bean protein in relation to their effects on serumcholesterol in rabbits. Br J Nutr,1985,54(2):355-366.
74West CE, Beynen AC, Scholz KE et al, Treatment of dietary casein with formaldehyde reduces itshypercholesterolemic effect in rabbits. J Nutr,1984,114(1):17-25.
75Yang L, Kadowaki M, Effects of rice proteins from two cultivars, koshihikari and shunyo, on hepaticcholesterol secretion by isolated perfused livers of rats fed cholesterol-enriched diets. Ann Nutr Metab,2009,54(4):283-290.
76Yang L, Kumagai T, Kawamura H et al, Effects of rice proteins from two cultivars, koshihikari and shunyo,on cholesterol and triglyceride metabolism in growing and adult rats. Biosci Biotechnol Biochem,2007,71(3):694-703.
77Kayashita J, Shimaoka I, Nakajoh M et al, Consumption of buckwheat protein lowers plasma cholesterol andraises fecal neutral sterols in cholesterol-fed rats because of its low digestibility. J Nutr,1997,127(7):1395-1400.
78Sugano M, Goto S, Yamada Y et al, Cholesterol-lowering activity of various undigested fractions of soybeanprotein in rats. J Nutr,1990,120(9):977-985.
79Wang MF, Yamamoto S, Chung HM et al, Antihypercholesterolemic effect of undigested fraction of soybeanprotein in young female volunteers. J Nutr Sci Vitaminol (Tokyo),1995,41(2):187-195.
80Zhang X, Beynen AC, Lowering effect of dietary milk-whey protein v. Casein on plasma and liver cholesterolconcentrations in rats. Br J Nutr,1993,70(1):139-146.
81Nagaoka S, Studies on regulation of cholesterol metabolism induced by dietary food constituents orxenobiotics. J Jpn Soc Nutr Food Sci,1996,49:303-313.
82Nishizawa K, Kita A, Doi C et al, Accumulation of the bioactive peptides, novokinin, lpypr and rubiscolin, inseeds of genetically modified soybean. Biosci Biotechnol Biochem,2008,72(12):3301-3305.
83Zhong F, Zhang X, Ma J et al, Fractionation and identification of a novel hypocholesterolemic peptide derivedfrom soybean protein alcalase hydrolysates. Food Res Int,2007,40(6):756-762.
84Nagaoka S, Nakamura A, Shibata H et al, Soystatin (vawwmy), a novel bile acid-binding peptide, decreasedmicellar solubility and inhibited cholesterol absorption in rats. Biosci Biotechnol Biochem,2010,74(8):1738-1741.
85Kati E, Belinda WYC, Henning S, The possible roles of food-derived bioactive peptides in reducing the risk ofcardiovascular disease. J Nutr Biochem,2008,19(10):643-654.
86Yoshikawa M, Fujita H, Matoba N et al, Bioactive peptides derived from food proteins preventing lifestyle-related diseases. Biofactors,2000,12(1-4):143-146.
87Cho SJ, Juillerat MA, Lee CH, Identification of ldl-receptor transcription stimulating peptides from soybeanhydrolysate in human hepatocytes. J Agric Food Chem,2008,56(12):4372-4376.
88Lovati MR, Manzoni C, Gianazza E et al, Soybean protein peptides regulate cholesterol homeostasis in hep g2cells. J Nutr,2000,130(10):2543-2549.
89Kritchevsky D, Dietary protein, cholesterol and atherosclerosis: A review of the early history. J Nutr,1995,125(3Suppl):589S-593S.
90Xiangdong L, Yuanwu L, Hua Z et al, Animal models for the atherosclerosis research: A review. Protein& Cell,2011,2(3):189-201.
91Beavers KM, Serra MC, Beavers DP et al, The lipid-lowering effects of4weeks of daily soymilk or dairymilk ingestion in a postmenopausal female population. J Med Food,2010,13(3):650-656.
92Fluegel SM, Shultz TD, Powers JR et al, Whey beverages decrease blood pressure in prehypertensive andhypertensive young men and women. Int Dairy J,2010,20(11):753-760.
93Carroll KK, Hamilton RMG, Effects of dietary protein and carbohydrate on plasma cholesterol levels inrelation to atherosclerosis. J Food Sci,1975,40(1):18-23.
94Beynen AC, Liepa GU, Dietary cottonseed protein and cholesterol metabolism. Zeitschrift für Ern hrungswis-senschaft,1987,26(4):219-225.
95Adebiyi A, Adebiyi A, Hasegawa Y et al, Isolation and characterization of protein fractions from deoiled ricebran. Eur Food Res Technol,2009,228:391-401.
96Tran L, Nicolosi RJ, Comparative effects of soy and rice protein concentrate on plasma lipoprotein levels andearly atherosclerosis in hamsters. FASEB J,1997,11:884.
97Hartmann R, Meisel H, Food-derived peptides with biological activity: From research to food applications.Curr Opin Biotechnol,2007,18(2):163-169.
98Sugano M, Yamada Y, Yoshida K et al, The hypocholesterolemic action of the undigested fraction of soybeanprotein in rats. Atherosclerosis,1988,72(2-3):115-122.
99Kris-Etherton P, Dietschy J, Design criteria for studies examining individual fatty acid effects on cardiovascu-lar disease risk factors: Human and animal studies. Am J Clin Nutr,1997,65(5):1590S-1596S.
100Ness GC, Gertz KR, Hepatic hmg-coa reductase expression and resistance to dietary cholesterol. Exp BiolMed,2004,229(5):412-416.
1Kannel WB, Castelli WP, Gordon T et al, Serum cholesterol, lipoproteins, and the risk of coronary heart disease.The framingham study. Ann Intern Med,1971,74(1):1-12.
2Ros E, Intestinal absorption of triglyceride and cholesterol. Dietary and pharmacological inhibition to reducecardiovascular risk. Atherosclerosis,2000,151(2):357-379.
3Ikeda I, Tanaka K, Sugano M et al, Inhibition of cholesterol absorption in rats by plant sterols. J Lipid Res,1988,29(12):1573-1582.
4Yoshikawa M, Fujita H, Matoba N et al, Bioactive peptides derived from food proteins preventing lifestyle-related diseases. Biofactors,2000,12(1-4):143-146.
5Zhong F, Zhang X, Ma J et al, Fractionation and identification of a novel hypocholesterolemic peptide derivedfrom soybean protein alcalase hydrolysates. Food Res Int,2007,40(6):756-762.
6Megías C, Pedroche J, del Mar Yust M et al, Sunflower protein hydrolysates reduce cholesterol micellarsolubility. Plant Foods Hum Nutr,2009,64(2):86-93.
7Lin YH, Tsai JS, Hung LB et al, Hypocholesterolemic effect of compounded freshwater clam proteinhydrolysate and gracilaria. Food Chem,2010,123(2):395-399.
8Nagaoka S, Futamura Y, Miwa K et al, Identification of novel hypocholesterolemic peptides derived frombovine milk [beta]-lactoglobulin. Biochem Biophys Res Commolun,2001,281(1):11-17.
9http://oatwell.com/mechanism-oat-beta-glucan.html.
10Lund EK, Gee JM, Brown JC et al, Effect of oat gum on the physical properties of the gastrointestinal contentsand on the uptake of d-galactose and cholesterol by rat small intestine in vitro. Br J Nutr,1989,62(1):91-101.
11Eastwood MA, Hamilton D, Studies on the adsorption of bile salts to non-absorbed components of diet.Biochim Biophys Acta,1968,152(1):165-173.
12Kahlon TS, de J. Berrios J, Smith GE et al, In vitro bile acid binding capacity of milled wheat bran and milledextruded wheat bran at five specific mechanical energy levels. Cereal Chem,2006,83(4):434-438.
13Camire ME, Zhao J, Violette DA, In vitro binding of bile acids by extruded potato peels. J Agric Food Chem,1993,41(12):2391-2394.
14Kahlon TS, Chow FI, Hypocholesterolemic effects of oat, rice, and barley dietary fibers and fractions. Cerealfoods world,1997,42(2):86-92.
15Yoshie-Stark Y, W sche A, In vitro binding of bile acids by lupin protein isolates and their hydrolysates. FoodChem,2004,88(2):179-184.
16Kongo-Dia-Moukala JU, Zhang H, Claver Irakoze P, In vitro binding capacity of bile acids by defatted cornprotein hydrolysate. Intl J Mol Sci,2011,12(2):1066-1080.
17Kahlon TS, Woodruff CL, In vitro binding of bile acids by soybean protein, pinto beans,black beans andwheat gluten. Food Chem,2002,79:425–429.
18Tsuzuki W, Absorption properties of micellar lipid metabolites into caco2cells. Lipids,2007,42(7):613-619.
19Field F, Albright E, Mathur S, Regulation of cholesterol esterification by micellar cholesterol in caco-2cells. JLipid Res,1987,28(9):1057-1066.
20Nagaoka S, Awano T, Nagata N et al, Serum cholesterol reduction and cholesterol absorption inhibition incaco-2cells by a soyprotein peptic hydrolyzate. Biosci Biotechnol Biochem,1997,61(2):354-356.
21Limpeanchob N, Trisat K, Duangjai A et al, Sericin reduces serum cholesterol in rats and cholesterol uptakeinto caco-2cells. J Agric Food Chem,2010,58(23):12519-12522.
22Metzger BT, Barnes DM, Reed JD, Insoluble fraction of buckwheat (fagopyrum esculentum moench) proteinpossessing cholesterol-binding properties that reduce micelle cholesterol solubility and uptake by caco-2cells. JAgric Food Chem,2007,55(15):6032-6038.
23Adler-Nissen J: A reivew of food protein hydrolysis-general issues. London: Elsevier,1986.122-123.
24Zhang F, Wang Z, Xu S, Macroporous resin purification of grass carp fish (ctenopharyngodon idella) scalepeptides with in vitro angiotensin-i converting enzyme (ace) inhibitory ability. Food Chem,2009,117(3):387-392.
25Kirana C, Rogers PF, Bennett LE et al, Naturally derived micelles for rapid in vitro screening of potentialcholesterol-lowering bioactives. J Agric Food Chem,2005,53(11):4623-4627.
26Reeves PG, Nielsen FH, Fahey GC, Ain-93purified diets for laboratory rodents: Final report of the americaninstitute of nutrition ad hoc writing commolittee on the reformulation of the ain-76a rodent diet. J Nutr,1993,123(11):1939-1951.
27Sugano M, Yamada Y, Yoshida K et al, The hypocholesterolemic action of the undigested fraction of soybeanprotein in rats. Atherosclerosis,1988,72(2-3):115-122.
28Zhong F, Liu J, Ma J et al, Preparation of hypocholesterol peptides from soybean protein and theirhypocholesterolemic effect in mice. Food Res Int,2007,40(6):661-667.
29Sparrow CP, Patel S, Baffic J et al, A fluorescent cholesterol analog traces cholesterol absorption in hamstersand is esterified in vivo and in vitro. J Lipid Res,1999,40(10):1747-1757.
30Nagaoka S, Miwa K, Eto M et al, Soybean protein peptic hydrolysate with bound phospholipids decreasesmicellar solubility and cholesterol absorption in rats and caco-2cells. J Nutr,1999,129(9):1725-1730.
31Moreau RA, Whitaker BD, Hicks KB, Phytosterols, phytostanols, and their conjugates in foods: Structuraldiversity, quantitative analysis, and health-promoting uses. Prog Lipid Res,2002,41(6):457-500.
1Xiangdong L, Yuanwu L, Hua Z et al, Animal models for the atherosclerosis research: A review. Protein&Cell,2011,2(3):189-201.
2Suckling KE, Jackson B, Animal models of human lipid metabolism. Prog Lipid Res,1993,32(1):1-24.
3Ness GC, Gertz KR, Hepatic hmg-coa reductase expression and resistance to dietary cholesterol. Exp Biol Med,2004,229(5):412-416.
4Kris-Etherton P, Dietschy J, Design criteria for studies examining individual fatty acid effects on cardiovasculardisease risk factors: Human and animal studies. Am J Clin Nutr,1997,65(5):1590S-1596S.
5Reeves PG, Nielsen FH, Fahey GC, AIN-93G purified diets for laboratory rodents: Final report of the americaninstitute of nutrition ad hoc writing commolittee on the reformulation of the ain-76a rodent diet. Journal ofNutrition,1993,123(11):1939-1951.
6German JB, Xu R, Walzem R et al, Effect of dietary fats and barley fiber on total cholesterol and lipoproteincholesterol distribution in plasma of hamsters. Nutr Res,1996,16(7):1239-1249.
7Villanueva MJ, Yokoyama WH, Hong YJ et al, Effect of high-fat diets supplemented with okara soybean by-product on lipid profiles of plasma, liver and faeces in syrian hamsters. Food Chem,2011,124(1):72-79.
8Van Der Meer R, Vries H, JFC G, T-butanol extraction of feces: Rapid procedure for enzymic determination offecal bile acids. The Netherlands: Posen and Looijen,1985.113-119.
9Yang L, Kumagai T, Kawamura H et al, Effects of rice proteins from two cultivars, koshihikari and shunyo, oncholesterol and triglyceride metabolism in growing and adult rats. Biosci Biotechnol Biochem,2007,71(3):694-703.
10Bong HY, Kim JY, Jeong HI et al, Effects of corn gluten hydrolyzates, branched chain amino acids, andleucine on body weight reduction in obese rats induced by a high fat diet. Nutr Res Pract,2010,4(2):106-113.
11Zhang Y, Guo K, LeBlanc RE et al, Increasing dietary leucine intake reduces diet-induced obesity andimproves glucose and cholesterol metabolism in mice via multimechanisms. Diabetes,2007,56(6):1647-1654.
12Cohn JS, Kimpton WG, Nestel PJ, The effect of dietary casein and soybean protein on cholesterol and verylow density lipoprotein metabolism in the rat. Atherosclerosis,1984,52(2):219-231.
13Robert K. Murray, David A Bender, Kathleen M. Botham et al. Harper's illustrated biochemistry. TheMcGraw-Hill Companies, Inc.,2009.430-470
14Sugano M, Tanaka K, Ide T, Secretion of cholesterol, triglyceride and apolipoprotein a-i by isolated perfusedliver from rats fed soybean protein and casein or their amino acid mixtures. J Nutr,1982,112(5):855-862.
15Pullen DL, Emery RS, Ames NK, Turnover of hepatic and plasma triacylglycerol in sheep. J Anim Sci,1988,66(6):1538-1547.
16Sugano M, Yamada Y, Yoshida K et al, The hypocholesterolemic action of the undigested fraction of soybeanprotein in rats. Atherosclerosis,1988,72(2-3):115-122.
17Galibois I, Jacques H, Montminy C et al, Independent effects of protein and fibre sources on glucose and cho-lesterol metabolism in the rat. Nutr Res,1992,12(4-5):643-655.
18Ahmed HA, Petroni ML, Abu-Hamdiyyah M et al, Hydrophobic/hydrophilic balance of proteins: A majordeterminant of cholesterol crystal formation in model bile. J Lipid Res,1994,35(2):211-219.
19Yamashita G, Secknus R, Chernosky ANN et al, Comparison of haptoglobin and apolipoprotein a-i on biliarylipid particles involved in cholesterol crystallization. J Gastroen Hepatol,1996,11(8):738-745.
20Spielmann J, Stangl GI, Eder K, Dietary pea protein stimulates bile acid excretion and lowers hepaticcholesterol concentration in rats. J Anim Physiol Anim Nutr (Berl),2008,92(6):683-693.
21Jacques H, Deshaies Y, Savoie L, Relationship between dietary proteins, their in vitro digestion products, andserum cholesterol in rats. Atherosclerosis,1986,61(2):89-98.
22Kritchevsky D, Vegetable protein and atherosclerosis. J Am Oil Chem Soc,1979,56(3):135-140.
23Morita T, Oh-hashi A, Takei K et al, Cholesterol-lowering effects of soybean, potato and rice proteins dependon their low methionine contents in rats fed a cholesterol-free purified diet. J Nutr,1997,127(3):470-477.
24Iwami K, Sakakibara K, Ibuki F, Involvement of post-digestion\'\'hydrophobia\'\'peptides in plasma cholesterollowering effect of dietary plant proteins. Agric Biol Chem,1986,50(5):1217-1222.
1Vahouny GV, Adamson I, Chalcarz W et al, Effects of casein and soybean protein on hepatic and serum lipidsand lipoprotein lipid distributions in the rat. Atherosclerosis,1985,56(2):127-137.
2Nagata Y, Ishiwaki N, Sugano M, Studies on the mechanism of antihypercholesterolemic action of soybeanprotein and soybean protein-type amino acid mixtures in relation to the casein counterparts in rats. J Nutr,1982,112(8):1614-1625.
3Tanaka K, Imaizumi K, Sugano M, Effects of dietary proteins on the intestinal synthesis and transport ofcholesterol and apolipoprotein a-i in rats. J Nutr,1983,113(7):1388-1394.
4Shukla A, Brandsch C, Bettzieche A et al, Isoflavone-poor soybean protein alters the lipid metabolism of ratsby srebp-mediated down-regulation of hepatic genes. J Nutr Biochem,2007,18(5):313-321.
5Yang L, Kumagai T, Kawamura H et al, Effects of rice proteins from two cultivars, koshihikari and shunyo, oncholesterol and triglyceride metabolism in growing and adult rats. Biosci Biotechnol Biochem,2007,71(3):694-703.
6Livak KJ, Schmittgen TD, Analysis of relative gene expression data using real-time quantitative pcr and the2-[delta][delta]ct method. Methods,2001,25(4):402-408.
7Everett L, Galli A, Crabb D, The role of hepatic peroxisome proliferator-activated receptors (ppars) in healthand disease. Liver,2000,20(3):191-199.
8Yang L, Kadowaki M, Effects of rice proteins from two cultivars, koshihikari and shunyo, on hepatic cholester-ol secretion by isolated perfused livers of rats fed cholesterol-enriched diets. Ann Nutr Metab,2009,54(4):283-290.
9Horton JD, Goldstein JL, Brown MS, Srebps: Activators of the complete program of cholesterol and fatty acidsynthesis in the liver. J Clin Invest,2002,109(9):1125-1131.
10Shimomura I, Shimano H, Horton JD et al, Differential expression of exons1a and1c in mrnas for sterolregulatory element binding protein-1in human and mouse organs and cultured cells. J Clin Invest,1997,99:838–845.
11Shimomura I, Matsuda M, Hammoler RE et al, Decreased irs-2and increased srebp-1c lead to mixed insulinresistance and sensitivity in livers of lipodystrophic and ob/ob mice. Mol Cell,2000,6(1):77-86.
12Schroder M, Kaufman RJ, The mammolalian unfolded protein response. Annu Rev Biochem,2005,74:739-789.
13Schultz JR, Tu H, Luk A et al, Role of lxrs in control of lipogenesis. Genes Dev,2000,14(22):2831-2838.
14Peet DJ, Turley SD, Ma W et al, Cholesterol and bile acid metabolism are impaired in mice lacking the nucle-ar oxysterol receptor lxrα. Cell,1998,93(5):693-704.
15Kalaany NY, Gauthier KC, Zavacki AM et al, Lxrs regulate the balance between fat storage and oxidation.Cell Metab,2005,1(4):231-244.
16Repa JJ, Liang G, Ou J et al, Regulation of mouse sterol regulatory element-binding protein-1c gene (srebp-1c)by oxysterol receptors, lxralpha and lxrbeta. Genes Dev,2000,14(22):2819-2830.
17Christy RJ, Yang VW, Ntambi JM et al, Differentiation-induced gene expression in3t3-l1preadipocytes:Ccaat/enhancer binding protein interacts with and activates the promoters of two adipocyte-specific genes. GenesDev,1989,3(9):1323-1335.
18Miyazaki M, Dobrzyn A, Sampath H et al, Reduced adiposity and liver steatosis by stearoyl-coa desaturasedeficiency are independent of peroxisome proliferator-activated receptor-α. J Biol Chem,2004,279(33):35017-35024.
19Lalloyer F, Pedersen TA, Gross B et al, Rexinoid bexarotene modulates triglyceride but not cholesterolmetabolism via gene-specific permissivity of the rxr/lxr heterodimer in the liver. Arterioscler Thromb Vasc Biol,2009,29(10):1488-1495.
20Cohn JS, Kimpton WG, Nestel PJ, The effect of dietary casein and soybean protein on cholesterol and verylow density lipoprotein metabolism in the rat. Atherosclerosis,1984,52(2):219-231.
21Pullen DL, Emery RS, Ames NK, Turnover of hepatic and plasma triacylglycerol in sheep. J Anim Sci,1988,66(6):1538-1547.
22Paton CM, Ntambi JM, Biochemical and physiological function of stearoyl-coa desaturase. Am J PhysiolEndocrinol Metab,2009,297(1):E28-E37.
23Ntambi JM, Miyazaki M, Stoehr JP et al, Loss of stearoyl-coa desaturase-1function protects mice againstadiposity. Proc Natl Acad Sci U S A,2002,99(17):11482-11486.
24Kim J, Park J, Hong S et al, Effect of corn gluten and its hydrolysate consumptions on weight reduction in ratsfed a high-fat diet. Nutr Res Pract,2009,3(3):200-207.
25Joseph SB, Laffitte BA, Patel PH et al, Direct and indirect mechanisms for regulation of fatty acid synthasegene expression by liver x receptors. J Biol Chem,2002,277(13):11019-11025.
26Loftus TM, Jaworsky DE, Frehywot GL et al, Reduced food intake and body weight in mice treated with fattyacid synthase inhibitors. Science,2000,288(5475):2379-2381.
27Shimano H, Sterol regulatory element-binding protein-1as a dominant transcription factor for gene regulationof lipogenic enzymes in the liver. Trends Cardiovasc Med,2000,10(7):275-278.
28Nguyen P, Leray V, Diez M et al, Liver lipid metabolism. J Anim Physiol An N,2008,92(3):272-283.
29Clarke SD, Thuillier P, Baillie RA et al, Peroxisome proliferator-activated receptors: A family of lipid-activat-ed transcription factors. Am J Clin Nutr,1999,70(4):566-571.
30Miyazaki M, Dobrzyn A, Sampath H et al, Reduced adiposity and liver steatosis by stearoyl-coa desaturasedeficiency are independent of peroxisome proliferator-activated receptor-a. J Biol Chem,2004:M405327200.
31Http://en.Wikipedia.Org/wiki/peroxisome_proliferator-activated_receptor
32Wang YX, Lee CH, Tiep S et al, Peroxisome-proliferator-activated receptor activates fat metabolism toprevent obesity. Cell,2003,113(2):159-170.
33Lee K, Villena JA, Moon YS et al, Inhibition of adipogenesis and development of glucose intolerance bysoluble preadipocyte factor–1(pref-1). J Clin Invest,2003,111(4):453-461.
34Kersten S, Seydoux J, Peters JM et al, Peroxisome proliferator-activated receptor alpha mediates the adaptiveresponse to fasting. J Clin Invest,1999,103(11):1489-1498.
35Fan CY, Pan J, Chu R et al, Hepatocellular and hepatic peroxisomal alterations in mice with a disruptedperoxisomal fatty acyl-coenzyme a oxidase gene. J Biol Chem,1996,271(40):24698-24710.
36Schrader M, Fahimi HD, The peroxisome: Still a mysterious organelle. Histochem Cell Biol,2008,129(4):421-440.
37Varanasi U, Chu R, Chu S et al, Isolation of the human peroxisomal acyl-coa oxidase gene: Organization,promoter analysis, and chromosomal localization. Proc Natl Acad Sci U S A,1994,91(8):3107-3111.
38Van Veldhoven PP, Vanhove G, Assselberghs S et al, Substrate specificities of rat liver peroxisomal acyl-coaoxidases: Palmitoyl-coa oxidase (inducible acyl-coa oxidase), pristanoyl-coa oxidase (non-inducible acyl-coaoxidase), and trihydroxycoprostanoyl-coa oxidase. J Biol Chem,1992,267(28):20065-20074.
39De Vries Y, Arvidson DN, Waterham HR et al, Functional characterization of mitochondrial carnitinepalmitoyltransferases i and ii expressed in the yeast pichia pastoris. Biochemistry (Mosc),1997,36(17):5285-5292.
40http://www.biocarta.com/pathfiles/m_cptPathway.asp
41Dobrzyn P, Dobrzyn A, Miyazaki M et al, Stearoyl-coa desaturase1deficiency increases fatty acid oxidationby activating amp-activated protein kinase in liver. Proc Natl Acad Sci U S A,2004,101(17):6409-6414.
42Lepesheva GI, Waterman MR, Cyp51--the omnipotent p450. Mol Cell Endocrinol,2004,215(1-2):165-170.
43Pikuleva IA, Cytochrome p450s and cholesterol homeostasis. Pharmacol Ther,2006,112(3):761-773.
44Chiang JYL, Bile acids: Regulation of synthesis. J Lipid Res,2009,50(10):1955-1966.
45Lehmann JM, Kliewer SA, Moore LB et al, Activation of the nuclear receptor lxr by oxysterols defines a newhormone response pathway. J Biol Chem,1997,272(6):3137-3140.
46De Fabiani E, Mitro N, Anzulovich AC et al, The negative effects of bile acids and tumor necrosis factor-α onthe transcription of cholesterol7α-hydroxylase gene (cyp7a1) converge to hepatic nuclear factor-4. J Biol Chem,2001,276(33):30708-30716.
47Dueland S, Reichen J, Everson GT et al, Regulation of cholesterol and bile acid homoeostasis in bile-obstructed rats. Biochem J,1991,280(Pt2):373-377.
48Nagano M, Kuroki S, Mizuta A et al, Regulation of bile acid synthesis under reconstructed enterohepaticcirculation in rats. Steroids,2004,69(10):701-709.
49Spady DK, Cuthbert JA, Willard MN et al, Adenovirus-mediated transfer of a gene encoding cholesterol7alpha-hydroxylase into hamsters increases hepatic enzyme activity and reduces plasma total and low densitylipoprotein cholesterol. J Clin Invest,1995,96(2):700-709.
50Li T, Matozel M, Boehme S et al, Overexpression of cholesterol7α-hydroxylase promotes hepatic bile acidsynthesis and secretion and maintains cholesterol homeostasis. Hepatology,2011,53(3):996-1006.
51Hayhurst GP, Lee YH, Lambert G et al, Hepatocyte nuclear factor4alpha (nuclear receptor2a1) is essentialfor maintenance of hepatic gene expression and lipid homeostasis. Mol Cell Biol,2001,21(4):1393-1403.
52Henkel A, Wei Z, Cohen DE et al, Mice overexpressing hepatic abcb11rapidly develop cholesterol gallstones.Mammol Genome,2005,16(12):903-908.
53Figge A, Lammolert F, Paigen B et al, Hepatic overexpression of murine abcb11increases hepatobiliary lipidsecretion and reduces hepatic steatosis. J Biol Chem,2004,279(4):2790-2799.
54Ananthanarayanan M, Balasubramanian N, Makishima M et al, Human bile salt export pump promoter istransactivated by the farnesoid x receptor/bile acid receptor. J Biol Chem,2001,276(31):28857-28865.
55Arrese M, Ananthanarayanan M, The bile salt export pump: Molecular properties, function and regulation.Pflugers Arch-Eur J Physiol,2004,449(2):123-131.
56Lagor WR, Millar JS, Overview of the ldl receptor: Relevance to cholesterol metabolism and future approach-es for the treatment of coronary heart disease. Journal of Receptor, Ligand and Channel Research,2010,3(1):1-14.
57Brow n MS, Goldstein JL, Cholesterol feedback: From schoenheimer's bottle to scap's meladl. J Lipid Res,2009,50(Supplement):S15-S27.
1Sirtori CR, Lovati MR, Manzoni C et al, Soy and cholesterol reduction: Clinical experience. J Nutr,1995,125(3Suppl):598S-605S.
2Sirtori CR, Even R, Lovati MR, Soybean protein diet and plasma cholesterol: From therapy to molecularmechanisms. Ann N Y Acad Sci,1993,676(1):188-201.
3Leveille GA, Fisher H, Plasma cholesterol in growing chicken as influenced by dietary protein and fat. ProcSoc Exp Biol Med,1958,98(3):630-632.
4Cohn JS, Kimpton WG, Nestel PJ, The effect of dietary casein and soybean protein on cholesterol and very lowdensity lipoprotein metabolism in the rat. Atherosclerosis,1984,52(2):219-231.
5Zhong F, Liu J, Ma J et al, Preparation of hypocholesterol peptides from soybean protein and theirhypocholesterolemic effect in mice. Food Res Int,2007,40(6):661-667.
6Wright SM, Salter AM, Effects of soybean protein on plasma cholesterol and bile acid excretion in hamsters.Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology,1998,119(2):247-254.
7L T, RJ N, Comparative effects of soy and rice protein concentrate on plasma lipoprotein levels and earlyatherosclerosis in hamsters. FASEB J,1997,11(Abstract):884.
8Hamilton RMG, Carroll KK, Plasma cholesterol levels in rabbits fed low fat, low cholesterol diets effects ofdietary proteins, carbohydrates and fibre from different sources. Atherosclerosis,24(1-2):47-62.
9Greaves KA, Wilson MD, Rudel LL et al, Consumption of soybean protein reduces cholesterol absorptioncompared to casein protein alone or supplemented with an isoflavone extract or conjugated equine estrogen inovariectomized cynomolgus monkeys. J Nutr,2000,130(4):820-826.
10Nishizawa K, Kita A, Doi C et al, Accumulation of the bioactive peptides, novokinin, lpypr and rubiscolin, inseeds of genetically modified soybean. Biosci Biotechnol Biochem,2008,72(12):3301-3305.
11Zhong F, Zhang X, Ma J et al, Fractionation and identification of a novel hypocholesterolemic peptide derivedfrom soybean protein alcalase hydrolysates. Food Res Int,2007,40(6):756-762.
12Nagaoka S, Nakamura A, Shibata H et al, Soystatin (vawwmy), a novel bile acid-binding peptide, decreasedmicellar solubility and inhibited cholesterol absorption in rats. Biosci Biotechnol Biochem,2010,74(8):1738-1741.
13Manzoni C, Duranti M, Eberini I et al, Subcellular localization of soybean7s globulin in hepg2cells and ldlreceptor up-regulation by its alpha' constituent subunit. J Nutr,2003,133(7):2149-2155.
14Lovati MR, Manzoni C, Gianazza E et al, Soybean protein peptides regulate cholesterol homeostasis in hep g2cells. J Nutr,2000,130(10):2543-2549.
15Cho SJ, Juillerat MA, Lee CH, Identification of ldl-receptor transcription stimulating peptides from soybeanhydrolysate in human hepatocytes. J Agric Food Chem,2008,56(12):4372-4376.
16Nass N, Schoeps R, Ulbrich-Hofmann R et al, Screening for nutritive peptides that modify cholesterol7α-hydroxylase expression. J Agric Food Chem,2008,56(13):4987-4994.
17Zaloga GP, Siddiqui RA, Biologically active dietary peptides. Mini Rev Med Chem,2004,4(8):815-821.
18Reeves PG, Nielsen FH, Fahey GC, AIN-93G purified diets for laboratory rodents: Final report of the americ-an institute of nutrition ad hoc writing commolittee on the reformulation of the ain-76a rodent diet. J Nutr,1993,123(11):1939-1951.
19Nagaoka S, Futamura Y, Miwa K et al, Identification of novel hypocholesterolemic peptides derived frombovine milk [beta]-lactoglobulin. Biochem Biophys Res Commolun,2001,281(1):11-17.
20Nagaoka S, Miwa K, Eto M et al, Soybean protein peptic hydrolysate with bound phospholipids decreasesmicellar solubility and cholesterol absorption in rats and caco-2cells. J Nutr,1999,129(9):1725-1730.
21Erdmann K, Cheung BWY, Schr der H, The possible roles of food-derived bioactive peptides in reducing therisk of cardiovascular disease. J Nutr Biochem,2008,19(10):643-654.
22Roberts PR, Burney JD, Black KW et al, Effect of chain length on absorption of biologically active peptidesfrom the gastrointestinal tract. Digestion,1999,60(4):332-337.
23Hayashi S, Miyazaki Y, Yamashita J et al, Soybean protein has no hypocholesterolemic action in mice becau-se it does not stimulate fecal steroid excretion in that species. Cell Mol Biol (Noisy-Le-Grand),1994,40(7):1021-1028.
24Twisk J, Gillian-Daniel DL, Tebon A et al, The role of the ldl receptor in apolipoprotein b secretion. J ClinInvest,2000,105(4):521-532.
25Innerarity TL, Ldl receptor's β-propeller displaces ldl. Science,2002,298(5602):2337-2339.
26Goldstein JL, Brown MS, The ldl receptor. Arterioscler Thromb Vasc Biol,2009,29(4):431-438.
27Michaely P, Zhao Z, Li WP et al, Identification of a vldl-induced, fdnpvy-independent internalizationmechanism for the ldlr. EMBO J,2007,26(14):3273-3282.
28Mahley RW, Hui DY, Innerarity TL et al, Chylomicron remnant metabolism. Role of hepatic lipoproteinreceptors in mediating uptake. Arteriosclerosis,1989,9(1Suppl):I14-18.
29Lagor WR, Millar JS, Overview of the ldl receptor: Relevance to cholesterol metabolism and future approach-es for the treatment of coronary heart disease. Journal of Receptor, Ligand and Channel Research,2010,3(1):1-14.
30Jones C, Garuti R, Michaely P et al, Disruption of ldl but not vldl clearance in autosomal recessivehypercholesterolemia. J Clin Invest,2007,117(1):165-174.
31Santamarina-Fojo S, Brewer H, Lipoprotein lipase: Structure, function and mechanism of action. Int J ClinLab Res,1994,24(3):143-147.
32http://en.wikipedia.org/wiki/Lipoprotein_lipase
33Santamarina-Fojo S, González-Navarro H, Freeman L et al, Hepatic lipase, lipoprotein metabolism, and ather-ogenesis. Arterioscler Thromb Vasc Biol,2004,24(10):1750-1754.
34Homanics GE, de Silva HV, Osada J et al, Mild dyslipidemia in mice following targeted inactivation of thehepatic lipase gene. J Biol Chem,1995,270(7):2974-2980.
35Komaromy M, Azhar S, Cooper AD, Chinese hamster ovary cells expressing a cell surface-anchored form ofhepatic lipase. J Biol Chem,1996,271(28):16906-16914.
36Diard P, Malewiak MI, Lagrange D et al, Hepatic lipase may act as a ligand in the uptake of artificial chylom-icron remnant-like particles by isolated rat hepatocytes. Biochem J,1994,299(Pt3):889-894.
37Dugi KA, Amar MJA, Haudenschild CC et al, In vivo evidence for both lipolytic and nonlipolytic function ofhepatic lipase in the metabolism of hdl. Arterioscler Thromb Vasc Biol,2000,20(3):793-800.
38Amar MJA, Dugi KA, Haudenschild CC et al, Hepatic lipase facilitates the selective uptake of cholesterylesters from remnant lipoproteins in apoe-deficient mice. J Lipid Res,1998,39(12):2436-2442.
39Yin L, Ma H, Ge X et al, Hepatic hepatocyte nuclear factor4{alpha} is essential for maintaining triglycerideand cholesterol homeostasis. Arterioscler Thromb Vasc Biol,2011,31(2):328-336.
40Horton JD, Goldstein JL, Brown MS, Srebps: Activators of the complete program of cholesterol and fatty acidsynthesis in the liver. J Clin Invest,2002,109(9):1125-1131.
