A soy protein diet alters hepatic lipid metabolism gene expression and reduces serum lipids and renal fibrogenic cytokines in rats with chronic nephrotic syndrome

Nephrotic syndrome (NS) is characterized by the presence of proteinuria and hyperlipidemia. However, ingestion of soy protein has a hypolipidemic effect. The present study was designed to determine whether the ingestion of a 20% soy protein diet regulates the expression of hepatic sterol regulatory element binding protein (SREBP)-1, fatty acid synthase (FAS), malic enzyme, beta-hydroxy-beta-methylglutaryl-CoA (HMG-CoA) reductase (r) and synthase (s), and LDL receptor (r), and to assess whether soy protein improves lipid and renal abnormalities in rats with chronic NS. Male Wistar rats were injected with vehicle or with puromycin aminonucleoside to induce NS and were fed either 20% casein or soy protein diets for 64 d. NS rats fed 20% soy protein had improved creatinine clearance and reduced proteinuria, hypercholesterolemia, hypertriglyceridemia, as well as VLDL-triglycerides and LDL cholesterol compared with NS rats fed the 20% casein diet. In addition, the soy protein diet decreased the incidence of glomerular sclerosis, and proinflammatory cytokines in kidney. Ingestion of the soy protein diet by control rats reduced the gene expression of SREBP-1, malic enzyme, FAS and increased HMG-CoAr, HMG-CoAs and LDLr. However, NS rats fed either casein or soy protein diets had low insulin concentrations with reductions in SREBP-1, FAS and malic enzyme expression compared with control rats fed the casein diet. NS rats fed the soy diet also had lower HMG-CoAr and LDLr mRNA levels than NS rats fed casein. In conclusion, the beneficial effects of soy protein on lipid metabolism are modulated in part by SREBP-1. However, in NS rats, the benefit may be through a direct effect of this protein on kidney rather than mediated by changes in expression of hepatic lipid metabolism genes.     

Soy protein ameliorates metabolic abnormalities in liver and adipose tissue of rats fed a high fat diet

Chronic consumption of high-fat or -carbohydrate diets is associated with the development of obesity; however, it is not well established whether dietary protein plays a role in the development of abnormalities of lipid metabolism that occur during obesity. To determine the effect of different types of protein during diet-induced obesity on hepatic and adipocyte lipid metabolism, rats were fed casein (CAS) or soy (SOY) protein diets with 5% fat or high-fat diets with 25% fat (HF-CAS and HF-SOY) for 180 d. Rats fed soy diets had lower hepatic sterol regulatory element binding protein-1 (SREBP-1) expression and higher SREBP-2 expression than those fed casein diets, leading to less hepatic lipid deposition. On the other hand, long-term HF-SOY consumption prevented hyperleptinemia in comparison with rats fed HF-CAS. Rats fed soy protein diet showed higher adipocyte perilipin mRNA expression and smaller adipocyte area than those fed casein diets, which was associated with a lower body fat content. Furthermore, the lipid droplet area in brown adipose tissue was significantly lower in rats fed soy diets than in those fed casein diets and it was associated with higher uncoupling protein-1 (UCP-1) expression. As a result, rats fed the soy diets gained less weight than those fed the casein diets, in part due to an increase in the thermogenic capacity mediated by UCP-1. These results suggest that the type of protein consumed and the presence of fat in the diet modulate lipid metabolism in adipose tissue and liver.     

大豆蛋白对高脂饲料喂养大鼠固醇调节元件结合蛋白基因表达的影响

目的探讨大豆蛋白在正常饮食和高脂饮食状态下对大鼠脂代谢相关固醇调节元件结合蛋白(SREBP)基因表达水平的影响。方法 48只清洁级SD大鼠,按体重随机分为4组,分别喂饲含酪蛋白和大豆蛋白的正常饲料和高脂饲料28d后,脱颈椎处死动物,检测激素指标及基因表达水平。结果大豆蛋白组大鼠血清胰岛素水平和胰岛素/胰高血糖素比值显著低于酪蛋白组(P<0.05);大豆蛋白高脂组大鼠血清胰岛素水平显著低于酪蛋白高脂组(P<0.05);大豆蛋白组和大豆蛋白高脂组大鼠肝脏SREBP-1,2基因表达均分别显著低于酪蛋白组和酪蛋白高脂组(P<0.05);大豆蛋白组和大豆蛋白高脂组大鼠肝脏SREBP-1蛋白表达明显低于酪蛋白组和酪蛋白高脂组(P<0.05)。结论大豆蛋白可能通过影响胰岛素进而影响SREBP-1基因表达来调节血脂水平。     

Effect of proteins from beef, pork, and turkey meat on plasma and liver lipids of rats compared with casein and soy protein

OBJECTIVE: We assessed the effect of dietary proteins isolated from beef, pork, and turkey meat on concentrations of cholesterol and triacylglycerols in plasma, lipoproteins, and liver and the composition of the microsomal membrane (fatty acids, phosphatidylcholine/phosphatidylethanolamine ratio) compared with that of casein and soy protein in rats. METHODS: Five groups of 12 rats each were fed semisynthetic diets for 20 d that contained 200 g/kg of proteins isolated from beef, pork, or turkey meat or, as controls, casein or soy protein. RESULTS: Rats fed beef, pork, or turkey proteins did not differ in cholesterol concentrations of plasma, lipoproteins, and liver and in composition of microsomal membrane from rats fed the casein diet. All groups fed a protein from an animal source had higher very low-density lipoprotein (VLDL) and liver cholesterol concentrations than did rats fed soy protein. However, rats fed pork protein had lower concentrations of triacylglycerols in liver, plasma, and VLDL and lower mRNA concentrations of sterol regulatory element binding protein-1 and glucose-6-phosphate dehydrogenase than did rats fed casein. However, concentrations of plasma and VLDL triacylglycerols in rats fed pork protein were not as low as those observed in rats fed soy protein. CONCLUSION: Proteins isolated from beef, pork, or turkey meat do not differ from casein in their effects on cholesterol metabolism. Pork protein decreases plasma triacylglycerol concentrations compared with casein but not compared with soy protein. The triacylglycerol-lowering effect of pork protein compared with casein is suggested to be caused by decreased hepatic fatty acid synthesis.     

乳清酸诱导大鼠脂肪肝的机制研究

目的研究乳清酸诱发大鼠脂肪肝的机制。方法将大鼠分成两组,对照组喂食AIN93标准饲料,模型组饲料中添加1%乳清酸。饲喂10d后,分别测定大鼠血清总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、高密度脂蛋白胆固醇(high density lipoprotein-cholesterol,HDL-C)含量,以及肝脏TC、TG、磷脂含量。同时测定了肝脏中脂肪酸合成酶(FAS)、肉碱棕榈酰转移酶(CPT)、微粒体甘油三酯转运蛋白(MTP)的活性和其mRNA表达量,以及固醇调节元件结合蛋白(SREBP-1c)和过氧化物酶体增殖物激活受体(PPARα)的mRNA表达量。结果乳清酸可显著提高大鼠血清TG浓度和肝脏TC、TG含量。添加乳清酸后,大鼠肝脏中FAS活性及mRNA水平明显上调,而CPT、MPT活性及mRNA水平明显下调,同时作为转录调节因子的SREBP-1cmRNA表达量增加3.13倍,PPARα mRNA表达量无明显变化。结论1%乳清酸诱发大鼠脂肪肝与SREBP-1c的表达量升高引发的脂肪合成亢进有关,并与脂肪酸氧化分解受抑制及MTP活性和基因表达量降低有关。     

Dietary fish protein alters blood lipid concentrations and hepatic genes involved in cholesterol homeostasis in the rat model

It is known that various dietary plant proteins are capable of influencing the lipid metabolism of human subjects and animals when compared with casein. Less, however, is known about the effects of fish protein on the cholesterol and triacylglycerol metabolism. Therefore, two experiments were conducted in which rats were fed diets containing 200 g of either fish protein, prepared from Alaska pollack fillets, or casein, which served as control, per kilogram, over 20 and 22 d, respectively. As parameters of lipid metabolism, the concentrations of cholesterol and triacylglycerols in the plasma and liver, the faecal excretion of bile acids and the hepatic expression of genes encoding proteins involved in lipid homeostasis were determined. In both experiments, rats fed fish protein had higher concentrations of cholesteryl esters in the liver, a lower concentration of cholesterol in the HDL fraction (rho > 1.063 kg/l) and lower plasma triacylglycerol concentrations than rats fed casein (P < 0.05). The gene expression analysis performed in experiment 2 showed that rats fed fish protein had higher relative mRNA concentrations of sterol regulatory element-binding protein (SREBP)-2, 3-hydroxy-3-methylglutaryl coenzyme A reductase, LDL receptor, apo AI, scavenger receptor B1 and lecithin-cholesterol-acyltransferase in their liver than did rats fed casein (P < 0.05). The faecal excretion of bile acids and the mRNA concentrations of cholesterol 7alpha-hydroxylase, SREBP-1c and corresponding target genes were not altered. These findings show that fish protein had multiple effects on plasma and liver lipids that were at least in part caused by an altered expression of the hepatic genes involved in lipid homeostasis.     

Lupin protein influences the expression of hepatic genes involved in fatty acid synthesis and triacylglycerol hydrolysis of adult rats

To assess the effect of lupin protein on concentrations of lipids in plasma lipoproteins and liver and hepatic mRNA concentrations of genes involved in lipid metabolism, adult rats were fed egg albumin-based diets containing either lupin protein from Lupinus albus or casein (50 g/kg) supplemented (hypercholesterolaemic) or not (normolipaemic) with a cholesterol-cholate mixture for 20 d. Lupin protein compared with casein lowered the concentrations of TAG in liver (P < 0.01) and circulating VLDL + chylomicrons (P < 0.05) of hypercholesterolaemic rats, but not of normolipaemic rats. Hepatic mRNA concentrations of genes involved in fatty acid synthesis such as sterol regulatory element-binding protein-1c, glucose-6-phosphate dehydrogenase, fatty acid synthase, stearoyl-CoA desaturase-1 and acyl-CoA:glycerol-3-phosphate acyltransferase were lower and mRNA concentrations of lipoprotein lipase, hepatic lipase and apoA5 involved in TAG hydrolysis were higher in rats fed lupin protein than in rats fed casein. These effects were stronger in hypercholesterolaemic rats than in normolipaemic rats. Hypercholesterolaemic rats fed the lupin protein had higher liver cholesterol concentrations (P < 0.01) and lower levels of LDL-cholesterol (P < 0.05) than rats fed casein. No effect of lupin protein was observed on cholesterol concentration in VLDL + chylomicrons and HDL and hepatic mRNA concentrations of genes involved in cholesterol and bile acid metabolism. In conclusion, the present study shows that lupin protein has hypotriacylglycerolaemic action possibly via down regulation of fatty acid synthesis genes and up regulation of genes involved in TAG hydrolysis. Alterations in cholesterol metabolism could not be explained on the basis of mRNA data.     

A casein diet added isoflavone-enriched soy protein favorably affects biomarkers of steatohepatitis in obese Zucker rats

ObjectiveDietary supplementation of a soy protein enriched with isoflavones (HDI) has been shown to improve fatty liver in obese rats. The main objective of this study was to investigate whether HDI would influence the inflammatory status in livers of obese rats with fatty liver.MethodsMale obese Zucker fa/fa rats were fed casein (controls) or casein supplemented with HDI (containing 4.00 g of genistein and 4.50 g of daidzein per kilogram of diet) for 6 wk.ResultsThe HDI-fed rats had a markedly lower hepatic concentration of triacylglycerol when compared with controls. The decreased aspartate transaminase/alanine transaminase ratio in plasma, together with lower circulating levels of alkaline phosphatase and bile acids after HDI feeding, implied an improved hepatitis. This was supported by decreased plasma and hepatic mRNA levels of tumor necrosis factor-α, lower plasma levels of interleukin-1β and monocyte chemoattractant protein-1, and an increased anti-inflammatory fatty acid index in plasma. HDI also seemed to protect the rats from oxidative damage, because the level of lipid peroxides in triacylglycerol-rich lipoproteins after in vitro copper oxidation was lower for HDI-fed rats when compared with controls.ConclusionThese results show that isoflavone-enriched soy protein favorably affects biomarkers of hepatic inflammation in obese Zucker fa/fa rats with fatty liver. Thus, dietary soy proteins enriched in isoflavones may be a promising agent to improve steatohepatitis in patients.     

Dietary whey protein downregulates fatty acid synthesis in the liver, but upregulates it in skeletal muscle of exercise-trained rats

OBJECTIVE: This study compared the effects of casein and whey protein as the source of dietary protein on the activity of lipogenic enzymes and mRNA levels in the liver and skeletal muscle of exercise-trained rats. METHODS: Twenty-eight male Sprague-Dawley rats were randomly assigned to one of four groups (n = 7/group). Rats were assigned to sedentary or exercise-trained groups and were fed the casein or whey protein diet. Rats in the exercise groups were trained for 2 wk using a swimming exercise for 120 min/d and 6 d/wk. RESULTS: A significant decrease in the activity of the hepatic lipogenic enzymes, glucose-6-phosphate dehydrogenase, malic enzyme, adenosine triphosphate citrate lyase, acetyl-coenzyme A carboxylase, and fatty acid synthase (FASN) was observed in rats fed whey protein compared with animals fed casein. Compared with the casein diet, the whey protein diet also lowered mRNA expression of these enzymes, except for FASN. In contrast to the findings in liver, whey protein, as compared with casein, increased skeletal muscle FASN activity and mRNA. Further, exercise training resulted in increased skeletal muscle glucose-6-phosphate dehydrogenase and FASN activity and adenosine triphosphate citrate lyase, acetyl-coenzyme A carboxylase-1, and FASN mRNA expression. CONCLUSIONS: Exercise training or whey protein may play an important role in suppressing hepatic fatty acid synthesis, thereby decreasing accumulation of body fat and stimulating the skeletal muscle to increase energy substrate as fat during prolonged exercise.     

Consumption of soy protein isolate modulates the phosphorylation status of hepatic ATPase/ATP synthase beta protein and increases ATPase activity in rats

ATPase/ATP synthase plays important roles in the regulation of carbohydrate, protein, and lipid metabolism through modulating energy homeostasis. The purpose of this study was to examine the effects of feeding soy proteins and isoflavones (ISF) on the enzymatic activity and protein modification of hepatic mitochondrial ATPase/ATP synthase. In Expt. 1, Sprague-Dawley rats aged 50 d were fed diets containing either 20% casein or 20% alcohol-washed soy protein isolate (SPI) with or without supplemental ISF (770.7 micromol/kg diet) for 70 d. In Expt. 2, weanling Sprague-Dawley rats were fed diets containing 20% casein with or without added ISF (154.1 micromol/kg diet) or 20% SPI for 90 d. Hepatic mitochondrial ATPase activity was significantly higher in the rats fed SPI than in those fed casein. Addition of ISF to SPI eliminated the action of SPI. ATPase/ATP synthase beta protein contents in the liver were unchanged; however, its patterns measured by 2-dimensional Western blot were different among dietary groups. The rats fed SPI or SPI plus ISF had 3 more major protein spots with the same molecular weights (80 kDa and 55 kDa) as those presented in the rats fed casein but with different isoelectric points. Pretreatment of hepatic mitochondrial proteins from the rats fed casein with alkaline phosphatase produced the same ATPase/ATP synthase beta patterns as observed in the SPI-fed rats and significantly elevated the ATPase activity. These results suggest that consumption of soy proteins increases hepatic ATPase activity, which might be a consequence of increased dephosphorylation or decreased phosphorylation of the mitochondrial ATPase/ATP synthase beta protein.     

Dietary soy protein isolate and isoflavones modulate hepatic thyroid hormone receptors in rats

Thyroid hormone receptors (TRs) are regulators of many genes involved in cholesterol and lipid metabolism. The purpose of this study was to examine the effect of soy protein isolate (SPI) and isoflavones on hepatic TRs in rats. In Expt. 1, Sprague-Dawley rats were fed diets containing either casein or alcohol-washed SPI with or without isoflavone supplementation (5-1250 mg/kg diet) for 70, 190, and 310 d. The offspring (F1) were fed the same diets as their parents (F0). In Expt. 2, Sprague-Dawley rats were fed diets containing casein or casein plus isoflavones (50-400 mg/kg diet) for 120 d. The mRNA and protein contents of the hepatic TRs were measured by semiquantitative RT-PCR and Western blot, respectively. TRalpha1, TRalpha2, and TRbeta2 contents were not affected by SPI. However, the content of the 52-kDa TRbeta1 protein, the major isoform present in the liver, was markedly increased by dietary SPI in both sexes of F0 and F1 compared with casein. The supplemental isoflavones had no effect on TRbeta1, whereas the high doses of isoflavones (250 and 1250 mg/kg diet) reduced the hepatic TRalpha1 protein content in F1 male rats on d 28. SPI had no effect on total T3 and T4 levels. However, higher dose of supplemental isoflavones markedly increased T4 level in female rats. Overall, this study demonstrates for the first time that SPI upregulates hepatic TRbeta1 expression, and that isoflavones reduce the hepatic TRalpha1 level in young male rats. The SPI-induced TRbeta1 may play a role in mediating the hypocholesterolemic and lipid-lowering actions of soy protein.     

Dietary soy protein isolate modifies hepatic retinoic acid receptor-beta proteins and inhibits their DNA binding activity in rats

Retinoic acid receptors (RAR) belong to the same nuclear receptor superfamily as thyroid hormone receptors (TR) that were previously shown to be modulated by dietary soy protein isolate (SPI). This study has examined the effect of dietary SPI and isoflavones (ISF) on hepatic RAR gene expression and DNA binding activity. In Expt. 1, Sprague-Dawley rats were fed diets containing 20% casein or 20% alcohol-washed SPI in the absence or presence of increasing amounts of ISF (5-1250 mg/kg diet) for 70, 190, or 310 d. In Expt. 2, weanling Sprague-Dawley rats were fed diets containing 20% casein with or without supplemental ISF (50 mg/kg diet) or increasing amounts of alcohol-washed SPI (5, 10, and 20%) for 90 d. Intake of soy proteins significantly elevated hepatic RARbeta2 protein content dose-dependently compared with a casein diet, whereas supplemental ISF had no consistent effect. Neither RARbeta protein in the other tissues measured nor the other RAR (RARalpha and RARgamma) in the liver were affected by dietary SPI, indicating a tissue and isoform-specific effect of SPI. RARbeta2 mRNA abundances were not different between dietary groups except that its expression was markedly suppressed in male rats fed SPI for 310 d. DNA binding activity of nuclear RARbeta was significantly attenuated and the isoelectric points of RARbeta2 were shifted by dietary SPI. Overall, these results show for the first time, to our knowledge, that dietary soy proteins affect hepatic RARbeta2 protein content and RARbeta DNA binding activity, which may contribute to the suppression of retinoid-induced hypertriglyceridemia by SPI as reported.     

Expressions of c-myc and insulin-like growth factor-1 mRNA in the liver of growing rats vary reciprocally in response to changes in dietary protein

To investigate molecular mechanisms of growth control by diets, we examined the effects of nutrition on the expression of c-myc and insulin-like growth factor-1 (IGF-1) genes in the liver of growing rats. In the first study, rats were fed either a 24% casein, 24% zein or protein-free diet, or were starved for 3 d. The levels of the two mRNAs in the tissues were then determined by Northern blot hybridization. In the liver, levels of the two mRNAs varied in a reciprocal anner in response to changes in either quantity or quality of diet. The expression of c-myc mRNA was greatly enhanced by consumption of the protein-free diet or by starvation, whereas the IGF-1 mRNA levels were reduced markedly by consumption of the zein diet or the protein-free diet or by starvation. In another study, the casein and zein diets were fed to rats that had been adapted to a 2-h meal-feeding pattern, first with nonpurifled diet for 10 d and then with the protein-free diet for 3 d before the experiment. In rats fed casein, the level of c-myc mRNA decreased 75% within 8 h after consumption of the casein diet, whereas the IGF-1 mRNA level increased 100% during that period. Consumption of the zein diet did not affect the level of either mRNA. Because quantity of food intake did not differ between the rats fed casein and those fed zein, expression of the two genes in the liver was affected by the quality of the protein consumed. These results indicate that quality and quantity of diets changed the expression of c-myc and IGF-1 genes and thus demonstrate the possibility that nutrition not only supplies material for body components but also affects the signal transduction for growth in young growing rats.     

Hepatic cysteine dioxygenase activity and sulfur amino acid metabolism in rats: possible indicators in the evaluation of protein quality

Experiments were carried out to examine the possibility that the sulfur amino acid metabolism of rats may be an indicator of the nutritional value of dietary protein. Rats were fed diets containing 8, 16 or 24% of gluten, soy protein or casein for 3 wk. Hepatic cysteine dioxygenase activity, hepatic concentration of glutathione, cysteine and taurine and urinary taurine were examined. In addition, the sulfur amino acid metabolism of rats fed these diets fortified with the appropriate first limiting amino acid for 7 d was also examined. High urinary taurine excretion was observed in the three gluten groups, whereas very low urinary taurine excretion was observed with up to 24% soy protein or up to 16% casein. The hepatic hepatic cysteine dioxygenase activities of the gluten diet groups were higher than those of corresponding soy protein or casein diet groups, except that of rats fed the 24% casein diet. The hepatic concentrations of both glutathione and cysteine in gluten diet groups were also higher than those of corresponding soy protein or casein diet groups, except 24% soy protein and 16 and 24% casein diet groups. In rats fed the casein or soy protein diets urinary taurine excretion and hepatic cysteine dioxygenase activity increased with increasing methionine supplementation, the first limiting amino acid. Conversely, in rats fed the gluten diet both urinary taurine excretion and hepatic cysteine dioxygenase activity decreased with increasing lysine supplementation, the first limiting amino acid. These findings suggest that urinary taurine excretion and hepatic cysteine dioxygenase activity may be useful as sensitive indicators of the nutritional value of dietary protein.     

Soy protein and fish oil independently decrease serum lipid concentrations but interactively reduce hepatic enzymatic activity and gene expression involved in fatty acid synthesis in rats

The degree of interaction between dietary protein and fat sources to modulate hepatic lipid metabolism was investigated. Male rats were fed diets containing either casein or soy protein isolate as the protein source and either palm or soy oil as the fat source. After 3 wk, the activity and mRNA expression of enzymes involved in hepatic fatty acid synthesis were significantly lower with soy protein than casein when palm oil was the fat source. The same values for the same enzymes were greatly lowered regardless of the protein source when fish oil was the fat source. Both enzymatic activity and mRNA expression for fatty acid oxidation were significantly stimulated by fish oil, but only the former was increased by soy protein. Although both soy protein and fish oil reduced serum lipid concentrations, they worked independently. In soy protein-fed rats, mRNA levels of key enzymes related to cholesterol and bile acid synthesis were decreased and increased, respectively, compared with levels in casein-fed animals. Instead, fish oil strongly induced the mRNA expression of biliary cholesterol transporters, ATP-binding cassette sub-family G, member 5 (ABCG5) and ATP-binding cassette sub-family G, member 8 (ABCG8). Therefore, dietary soy protein and fish oil generally exerted independent hypolipidemic actions in rats. However, the reduction of hepatic fatty acid synthesis caused by the simultaneous ingestion of soy protein and fish oil was smaller than their expected additive reduction, because fish oil strongly decreased the synthesis.     

Fish protein hydrolysate reduces plasma total cholesterol, increases the proportion of HDL cholesterol, and lowers acyl-CoA:cholesterol acyltransferase activity in liver of Zucker rats

There is growing evidence that soy protein improves the blood lipid profiles of animals and humans. We compared the effects of fish protein hydrolysate (FPH), soy protein, and casein (control) on lipid metabolism in Wistar rats and genetically obese Zucker (fa/fa) rats. In Zucker rats, FPH treatment affected the fatty acid composition in liver, plasma, and triacylglycerol-rich lipoproteins. The mRNA levels of Delta 5 and Delta 6 desaturases were reduced by FPH and soy protein feeding compared with casein feeding. In Zucker rats both FPH and soy protein treatment reduced the plasma cholesterol level. Furthermore, the HDL cholesterol:total cholesterol ratio was greater in these rats and in the Wistar rats fed FPH and soy protein compared with those fed casein. Although fecal total bile acids were greater in soy protein-fed Zucker rats than in casein-fed controls, those fed FPH did not differ from the controls. However, the acyl-CoA:cholesterol acyltransferase activity was reduced in Zucker rats fed FPH and tended to be lower (P = 0.13) in those fed soy protein compared with those fed casein. Low ratios of methionine to glycine and lysine to arginine in the FPH and soy protein diets, compared with the casein diet, may be involved in lowering the plasma cholesterol concentration. Our results indicate that the effects of FPH and soy protein on fatty acid metabolism are similar in many respects, but the hypocholesterolemic effects of FPH and soy protein appear to be due to different mechanisms. FPH may have a role as a cardioprotective nutrient.     

Effects of dietary proteins on lipogenic enzymes in rat liver

When fasted rats were fed fat-free diets containing various sources of protein for 3 d, the activities of liver glucose-6-phosphate dehydrogenase, malic enzyme, acetyl-CoA carboxylase and fatty acid synthetase were markedly lower in rats fed soybean protein or gluten than in those fed casein or fish protein. Since malic enzyme mRNA activity was not low in the soybean protein-fed animals, the translation of malic enzyme appears to be suppressed by dietary soybean protein. The incorporation of tritiated water into liver fatty acids was significantly lower in animals fed soybean protein than in those fed casein. The triglyceride levels in plasma and especially in liver were also lower in the groups fed soybean and gluten than in the groups fed casein and fish. In addition, when dietary soybean protein was replaced with amino acids to simulate casein or soybean protein, the effects on the levels of lipogenic enzymes were still found but were not as great. Thus, some effects can be ascribed to the protein itself and some to the amino acid composition of the diet.     

Dietary polyunsaturated fats regulate rat liver sterol regulatory element binding proteins-1 and -2 in three distinct stages and by different mechanisms

Male Sprague-Dawley rats, trained to consume their daily energy needs in a single 3-h meal (0900-1200 h), were used to examine the hypothesis that polyunsaturated fatty acids (PUFA) lowered the nuclear content of sterol regulatory element binding protein (SREBP)-1 and/or -2 by suppressing the proteolytic release of mature SREBP from the membrane-anchored precursor pool. The nuclear concentrations of hepatic SREBP-1 and -2 were 50 and 42% lower (P < 0.05) in rats that consumed a single PUFA-supplemented meal (i.e., 10 g fish oil/100 g fat-free diet) than in rats fed the fat-free diet alone. This was paralleled by 63 and 52% reductions in the expression of the SREBP-1 and -2 target genes, fatty acid synthase and HMG-CoA synthase, respectively; but the marked increase in the amount of precursor SREBP-1 and -2 resulting from meal ingestion was unaffected. After the consumption of a second meal of fish oil, the nuclear level of mature SREBP-1 was only 16% of that in rats fed the fat-free diet, but the amount of nuclear SREBP-2 was not different from the level in rats fed the fat-free diet. Again, the sizes of the SREBP-1 and -2 precursor pools were not reduced. A decrease in the hepatic concentration of precursor SREBP-1 did not occur until rats had consumed 5 meals of fish oil. At this point, the nuclear content of SREBP-2 was actually twofold higher (P < 0.05) in rats fed fish oil or safflower oil, but the amount of precursor SREBP-2 was unaffected. These data indicate that PUFA suppress the in vivo proteolytic release of SREBP-1 and -2, but the effect on SREBP-2 is transitory, possibly reflecting the ability of PUFA to enhance cholesterol losses via bile acid synthesis.     

Effect of cholesterol supplementation on plasma and liver cholesteryl ester fatty acids in rats fed casein or soy protein

The effect of supplementation with cholesterol on plasma and liver cholesteryl ester fatty acids was examined in rats fed diets containing different protein sources. Weanling male rats were fed a semi-purified diet containing 20% casein or 20% soy protein for seven weeks and then 1% (by weight) of cholesterol was added for three more weeks. Rats fed soy protein grew consistently slower than those fed casein. The plasma and liver cholesterol contents were not significantly different between the two protein groups in the unsupplemented rats; however, they were significantly increased in cholesterol-fed animals, particularly in casein-fed rats. Analysis of the cholesteryl ester fatty acid composition in plasma and liver demonstrated that cholesterol-feeding significantly increased the levels of saturated fatty acids, monounsaturated fatty acids and linoleic acid in casein-fed rats as compared to those fed soy protein. The level of cholesteryl arachidonate in liver, which was low initially, increased slightly in the liver of casein-fed rats but did not significantly change in the plasma of either protein group.