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Dietary soya protein concentrate enriched with isoflavones reduced fatty liver, increased hepatic fatty acid oxidation and decreased the hepatic mRNA level of VLDL receptor in obese Zucker rats

Published online by Cambridge University Press:  08 March 2007

Oddrun A. Gudbrandsen*
Affiliation:
Institute of Medicine, Section of Medical Biochemistry, University of Bergen, Haukeland University Hospital, N-5021 Bergen, Norway
Hege Wergedahl
Affiliation:
Institute of Medicine, Section of Medical Biochemistry, University of Bergen, Haukeland University Hospital, N-5021 Bergen, Norway
Sverre Mørk
Affiliation:
Gade Institute, Department of Pathology, University of Bergen, Haukeland University Hospital, N-5021 Bergen, Norway
Bjørn Liaset
Affiliation:
National Institute of Nutrition and Seafood Research, Box 2029 Nordnes, N-5817 Bergen, Norway
Marit Espe
Affiliation:
National Institute of Nutrition and Seafood Research, Box 2029 Nordnes, N-5817 Bergen, Norway
Rolf K. Berge
Affiliation:
Institute of Medicine, Section of Medical Biochemistry, University of Bergen, Haukeland University Hospital, N-5021 Bergen, Norway
*
*Corresponding author: Dr Oddrun A. Gudbrandsen, fax +47 55973115, email nkjgu@uib.no
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Abstract

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Casein-based diets containing a low (LDI) or high (HDI) dose of soya protein concentrate enriched with isoflavones were fed to obese Zucker rats for 6 weeks. HDI feeding, but not LDI feeding, reduced the fatty liver and decreased the plasma levels of alanine transaminase and aspartate transaminase. This was accompanied by increased activities of mitochondrial and peroxisomal β-oxidation, acetyl-CoA carboxylase, fatty acid synthase and glycerol-3-phosphate acyltransferase in liver and increased triacylglycerol level in plasma. The decreased fatty liver and the increased plasma triacylglycerol level appeared not to be caused by an increased secretion of VLDL, as HDI decreased the hepatic mRNA levels of apo B and arylacetamide deacetylase. However, the gene expression of VLDL receptor was markedly decreased in liver, but unchanged in epididymal white adipose tissue and skeletal muscle of rats fed HDI, indicating that the liver may be the key organ for the reduced clearance of triacylglycerol-rich lipoproteins from plasma after HDI feeding. The n−3/n−6, 20:4n-/8:2n−6 and (20:5n−3+22:6n−3)/18:3n−3 ratios were increased in liver triacylglycerol by HDI. The phospholipids in liver of rats fed HDI contained a low level of 20:4n−6 and a high level of 20:5n−3, favouring the production of anti-inflammatory eicosanoids. When obese Zucker rats were fed soya protein, this also resulted in reduced fatty liver, possibly through reduced clearance of VLDL by the liver. We conclude that the isoflavone-enriched soya concentrate as well as soya protein may be promising dietary supplements for treatment of non-alcoholic fatty liver.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2006

References

Ali, AA, Velasquez, MT, Hansen, CT, Mohamed, AI & Bhathena, SJEffects 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 583590CrossRefGoogle Scholar
Anderson, JW, Johnstone, BM & Cook-Newell, MEMeta-analysis of the effects of soy protein intake on serum lipids. N Engl J Med (1995) 333 276282CrossRefGoogle ScholarPubMed
Angulo, P & Lindor, KDNon-alcoholic fatty liver disease. J Gastroenterol Hepatol (2002) 17 S186S190CrossRefGoogle ScholarPubMed
Balmir, F, Staack, R, Jeffrey, E, Jimenez, MD, Wang, L & Potter, SMAn extract of soy flour influences serum cholesterol and thyroid hormones in rats and hamsters. J Nutr (1996) 126 30463053CrossRefGoogle Scholar
Bates, EJ & Saggerson, DA selective decrease in mitochondrial glycerol phosphate acyltransferase activity in livers from streptozotocin-diabetic rats. FEBS Lett (1977) 84 229232CrossRefGoogle ScholarPubMed
Berge, RK, Flatmark, T & Osmundsen, HEnhancement of longchain acyl-CoA hydrolase activity in peroxisomes and mitochondria of rat liver by peroxisomal proliferators. Eur J Biochem (1984) 141 637644CrossRefGoogle ScholarPubMed
Bligh, EG & Dyer, WJA rapid method of total lipid extraction and purification. Can J Biochem Physiol (1959) 37 911917CrossRefGoogle ScholarPubMed
Bray, GAThe Zucker-fatty rat: a review. Fed Proc (1977) 36 148153Google ScholarPubMed
Brown, MS & Goldstein, JLA receptor-mediated pathway for cholesterol homeostasis. Science (1986) 232 3447CrossRefGoogle ScholarPubMed
Clarke, SDPolyunsaturated fatty acid regulation of gene transcription: a molecular mechanism to improve the metabolic syndrome. J Nutr (2001) 131 11291132CrossRefGoogle ScholarPubMed
Clinkenbeard, KD, Reed, WD, Mooney, RA & Lane, MDIntracellular localization of the 3-hydroxy-3-methylglutaryl coenzyme A cycle enzymes in liver. Separate cytoplasmic and mitochondrial 3-hydroxy-3-methylglutaryl coenzyme A generating systems for cholesterogenesis and ketogenesis. J Biol Chem (1975) 250 31083116CrossRefGoogle Scholar
Cohen, P & Friedman, JMLeptin and the control of metabolism:role for stearoyl-CoA desaturase-1 (SCD-1) J Nutr (2004) 134 2455S2463SCrossRefGoogle ScholarPubMed
Fukui, K, Tachibana, N, Wanezaki, S, Tsuzaki, S, Takamatsu, K, Yamamoto, T, Hashimoto, Y & Shimoda, TIsoflavone-free soy protein prepared by column chromatography reduces plasma cholesterol in rats. J Agric Food Chem (2002) 50 57175721CrossRefGoogle ScholarPubMed
Gidez, LI, Roheim, PS & Eder, HAEffect of diet on the cholesterol ester composition of liver and of plasma lipoproteins in the rat. J Lipid Res (1965) 6 377382CrossRefGoogle ScholarPubMed
Gudbrandsen, OA, Wergedahl, H, Liaset, B, Espe, M & Berge, RKDietary 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 321330CrossRefGoogle ScholarPubMed
Huff, MW, Hamilton, RM & Carroll, KKPlasma cholesterol levels in rabbits fed low fat, cholesterol-free, semipurified diets:effects of dietary proteins, protein hydrolysates and amino acid mixtures. Atherosclerosis (1977) 28 187195CrossRefGoogle ScholarPubMed
Krief, S & Bazin, RGenetic obesity: is the defect in the sympathetic nervous system? A review through developmental studies in the preobese Zucker rat. Proc Soc Exp Biol Med (1991) 198 528538CrossRefGoogle ScholarPubMed
Kritchevsky, D, Tepper, SA, Czarnecki, SK & Klurfeld, DMAtherogenicity of animal and vegetable protein. Influence of the lysine to arginine ratio. Atherosclerosis (1982) 41 429431CrossRefGoogle ScholarPubMed
McClain, CJ, Mokshagundam, SP, Barve, SS, Song, Z, Hill, DB, Chen, T & Deaciuc, IMechanisms of non-alcoholic steatohepatitis. Alcohol (2004) 34 6779CrossRefGoogle ScholarPubMed
Madani, S, Lopez, S, Blond, JP, Prost, J & Belleville, JHighly purified soybean protein is not hypocholesterolemic in rats but stimulates cholesterol synthesis and excretion and reduces polyunsaturated fatty acid biosynthesis. J Nutr (1998) 128 10841091CrossRefGoogle Scholar
Madsen, L, Froyland, L, Dyroy, E, Helland, K & Berge, RKDocosahexaenoic and eicosapentaenoic acids are differently metabolized in rat liver during mitochondria and peroxisome proliferation. J Lipid Res (1998) 39 583593CrossRefGoogle ScholarPubMed
Mangold, HK Aliphatic lipids in thin-layer chromatography. In A Laboratory Handbook, 2nd ed., [Stahl, E, editor]. Berlin: Springer (1969) 363421Google Scholar
Mezei, O, Banz, WJ, Steger, RW, Peluso, MR, Winters, TA & Shay, NSoy isoflavones exert antidiabetic and hypolipidemic effects through the PPAR pathways in obese Zucker rats and murine RAW 264·7 cells. J Nutr (2003) 133 12381243CrossRefGoogle ScholarPubMed
Morita, T, Oh-hashi, A, Takei, K, Ikai, M, Kasaoka, S & Kiriyama, SCholesterol-lowering effects of soybean, potato and rice proteins depend on their low methionine contents in rats fed a cholesterol-free purified diet. J Nutr (1997) 127 470477CrossRefGoogle ScholarPubMed
Morrison, WR & Smith, LMPreparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride–methanol. J Lipid Res (1964) 5 600608CrossRefGoogle ScholarPubMed
Muna, ZA, Gudbrandsen, OA, Wergedahl, H, Bohov, P, Skorve, J & Berge, RKInhibition of rat lipoprotein oxidation after tetradecylthioacetic acid feeding. Biochem Pharmacol (2002) 63 11271135CrossRefGoogle ScholarPubMed
Oka, K, Ishimura-Oka, K, Chu, MJ,Sullivan, M, Krushkal, J, Li, WH & Chan, LMouse very-low-density-lipoprotein receptor (VLDLR) cDNA cloning, tissue-specific expression and evolutionary relationship with the low-density-lipoprotein receptor. Eur J Biochem (1994) 224 975982CrossRefGoogle ScholarPubMed
Peluso, MR, Winters, TA, Shanahan, MF & Banz, WJA 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 23332342CrossRefGoogle ScholarPubMed
Potter, SMOverview of proposed mechanisms for the hypocholesterolemic effect of soy. J Nutr (1995) 125 606S611SGoogle ScholarPubMed
Roncari, DAFatty acid synthase from human liver. Methods Enzymol (1981) 71 Pt C, 7379CrossRefGoogle ScholarPubMed
Silverman, JF, O'Brien, KF, Long, S, Leggett, N, Khazanie, PG, Pories, WJ, Norris, HT & Caro, JFLiver pathology in morbidly obese patients with and without diabetes. Am J Gastroenterol (1990) 85 13491355Google ScholarPubMed
Sirtori, CR, Even, R & Lovati, MRSoybean protein diet and plasma cholesterol: from therapy to molecular mechanisms. Ann N Y Acad Sci (1993) 676 188201CrossRefGoogle ScholarPubMed
Skorve, J, al-Shurbaji, A, Asiedu, D, Bjorkhem, I, Berglund, L & Berge, RKOn the mechanism of the hypolipidemic effect of sulfur-substituted hexadecanedioic acid (3-thiadicarboxylic acid) in normolipidemic rats. J Lipid Res (1993) 34 11771185CrossRefGoogle ScholarPubMed
Small, GM, Burdett, K & Connock, MJA sensitive spectrophotometric assay for peroxisomal acyl-CoA oxidase. Biochem J (1985) 227 205210CrossRefGoogle ScholarPubMed
Tanabe, T, Nakanishi, S, Hashimoto, T, Ogiwara, H, Nikawa, J & Numa, SAcetyl-CoA carboxylase from rat liver. Methods Enzymol (1981) 71 Pt C 516CrossRefGoogle ScholarPubMed
Trickett, JI, Patel, DD, Knight, BL, Saggerson, ED, Gibbons, GF & Pease, RJCharacterization of the rodent genes for arylacetamide deacetylase, a putative microsomal lipase, and evidence for transcriptional regulation. J Biol Chem (2001) 276 3952239532CrossRefGoogle ScholarPubMed
Triscari, J, Greenwood, MR & Sullivan, ACOxidation and ketogenesis in hepatocytes of lean and obese Zucker rats. Metabolism (1982) 31 223228CrossRefGoogle ScholarPubMed
Videla, LA, Rodrigo, R, Araya, J & Poniachik, JOxidative stress and depletion of hepatic long-chain polyunsaturated fatty acids may contribute to nonalcoholic fatty liver disease. Free Radic Biol Med (2004) 37 14991507CrossRefGoogle ScholarPubMed
Wergedahl, H, Liaset, B, Gudbrandsen, OA, Lied, E, Espe, M, Muna, Z, Mork, S & Berge, RKFish protein hydrolysate reduces plasma total cholesterol, increases the proportion of HDL cholesterol, and lowers acyl-CoA:cholesterol acyltransferase activity in liver of Zucker rats. J Nutr (2004) 134 13201327CrossRefGoogle ScholarPubMed
Wiggins, D & Gibbons, GFOrigin of hepatic very-low-density lipoprotein triacylglycerol: the contribution of cellular phospholipid. Biochem J (1996) 320 Pt 2 673679CrossRefGoogle ScholarPubMed
Willumsen, N, Hexeberg, S, Skorve, J, Lundquist, M & Berge, RKDocosahexaenoic acid shows no triglyceride-lowering effects but increases the peroxisomal fatty acid oxidation in liver of rats. J Lipid Res (1993) 34 1322CrossRefGoogle ScholarPubMed