大豆活性肽降低大鼠血浆胆固醇机理的初步探讨

目的探讨膳食大豆活性肽对高胆固醇模型大鼠血浆胆固醇及其有关血脂指标的影响,并对其可能的作用机理加以研究。方法4周龄断乳雄性Wistar大鼠,经28d诱导高胆固醇模型以后,按血浆总胆固醇浓度将动物均衡分为2组,分别喂饲含酪蛋白和大豆活性肽的纯合成高脂饲料56d。结果经28d诱导高胆固醇模型后,高胆固醇模型大鼠的TC浓度是阴性对照组的1.51倍。又经56d喂饲含有处理因素的饲料后,酪蛋白组和大豆活性肽组大鼠体重分别增加了（198.5和119.3）g;血浆总胆固醇浓度水平分别为（6.41±0.57和3.01±0.37）mmol/L;TG水平分别为（3.73±0.70和2.13±0.61）mmol/L;粪胆汁酸含量分别为（0.75±0.13和0.96±0.17）mmol/d;与酪蛋白组相比,大豆活性肽组动物体重及TC,TG和apoB含量显著降低,而粪胆汁酸含量显著增加（P〈0.05）。大豆活性肽组可使大鼠肝脏HMG-CoA还原酶 mRNA,LDL-R mRNA的表达增强。结论膳食大豆活性肽摄入可降低高胆固醇模型大鼠TC、TG、apoB浓度、使粪胆汁酸排泄量增高,但对HDL-C,apoA水平无影响。另外,大豆活性肽可以增强大鼠肝脏HMG-CoA还原酶及LDL-R基因的表达,这可能是其降低血浆胆固醇的机理之一。大豆活性肽可影响血浆胆固醇水平,但其相应的作用机理还需进一步探讨。     

The hypocholesterolemic activity of Momordica charantia fruit is mediated by the altered cholesterol- and bile acid–regulating gene expression in rat liver

Although many studies have demonstrated the hypocholesterolemic activity of Momordica charantia, also called bitter gourd fruit (BGF), the relative hypocholesterolemic mechanism is not fully understood. In the present study, we hypothesized that BGF alters hepatic gene expression of cholesterol- and bile acid–regulating proteins to improve blood cholesterol profiles. To clarify the mechanism, we fed 7-week-old male Wistar rats a high-cholesterol (HC) diet containing 5% BGF for 4 weeks and determined the cholesterol levels in the serum, liver and feces, concentrations of the fecal total bile acid, and the expression level of cholesterol- and bile acid–regulating genes. The HC diet with BGF supplementation showed a significant serum hypocholesterolemic activity compared with the HC diet without BGF. BGF intake also significantly increased the levels of fecal total bile acid, suggesting that BGF inhibited the reabsorption of bile acids into the intestine. Hepatic messenger RNA (mRNA) levels of small heterodimer partner (SHP) and liver receptor homolog-1, which are both involved in cholesterol 7α-hydroxylase (CYP7A1) regulation, were significantly decreased and increased, respectively, by BGF intake. In addition, BGF tended to increase the hepatic CYP7A1 mRNA level. Taken together, these results suggest that BGF not only decreases the reabsorption of bile acids into the intestine but also increases the conversion of cholesterol to bile acids by CYP7A1 up-regulation through the down-regulation of the hepatic farnesoid X receptor/SHP pathway.     

甲鱼蛋粉调节大鼠血清胆固醇的基础研究

目的　研究甲鱼蛋粉对高胆固醇血症大鼠血清胆固醇的调节作用。方法　将 5 0只健康雄性SD大鼠按体重和血清胆固醇水平随机分成 5组 ,每组 10只 ,分别接受正常饲料、高脂饲料、高脂饲料加甲鱼蛋粉灌胃 (低、中、高剂量分别为 0 75、1 5 0、3 0 0 kgBW)处理 ,实验周期为 2 4周 ,实验期末 ,收集大鼠粪便 ,股动脉取血 ,酶法测定血清胆固醇 (TC)、高密度脂蛋白胆固醇 (HDL C)和低密度脂蛋白胆固醇 (LDL C)的含量 ,气相色谱法检测粪便胆固醇、粪甾醇、粪甾烯 ,循环酶法测定总胆汁酸的含量。结果　与高脂饲料组相比 ,中剂量和高剂量的甲鱼蛋粉均能显著降低 (P <0 0 5 )高胆固醇血症大鼠血清TC ,且剂量为 1 5 0g kgBW时能显著降低血清LDL水平 ;两剂量组均显著增加粪便胆固醇、粪甾醇和粪甾烯以及胆汁酸的排出。结论　甲鱼蛋粉是通过增加粪便固醇类以及胆汁酸的排出来达到降低模型大鼠血清胆固醇的作用     

大豆蛋白对大鼠血浆胆固醇影响及作用机制

目的探讨膳食大豆蛋白对高胆固醇模型大鼠血浆胆固醇及其相关血脂指标的影响及可能的作用机制。方法4周龄断乳雄性Wistar大鼠，诱导高胆固醇模型28d后，按体重和血浆总胆固醇浓度均衡分为2组，分别喂饲含酪蛋白和大豆蛋白的纯合成高脂饲料56d。结果酪蛋白组和大豆蛋白组大鼠TC、甘油三酯（TG）、载脂蛋白B（apoB）含量显著降低，粪胆汁酸排泄量增高。但对高密度脂蛋白胆固醇（鼢L—C），载脂蛋白AⅠ（apoA—Ⅰ）zk平无影响；同时可见，大豆蛋白可以增强大鼠肝脏3-羟基-3-甲酰基CoA（HMG—CoA）还原酶及低密度脂蛋白受体（LDL—R）基因的表达。结论大豆蛋白可通过影响apoB、HMG—CoA还原酶及LDL—R基因的表达来改变血浆胆固醇水平，其作用机制还需进一步探讨。     

Investigation of gene expressions related to cholesterol metabolism in rats fed diets enriched in n-6 or n-3 fatty acid with a cholesterol after long-term feeding using quantitative-competitive RT-PCR analysis

We have developed a method to quantitate hepatic apolipoprotein (apo) B, LDL receptor, 3-hydroxy-3-methylglutary coenzyme A reductase (HMG-CoA reductase) and cholesterol 7alpha-hydroxylase mRNA expression in rats fed a cholesterol-enriched diet after long-term feeding using competitive RT-RCR. Rats (8 wk of age) fed a conventional diet were shifted to diets containing 10% perilla oil (PEO, oleic acid+linoleic acid+alpha-linolenic acid), borage oil (BRO, oleic acid+linoleic acid+gamma-linolenic acid), evening primrose oil (EPO, linoleic acid+gamma-linolenic acid), mixed oil (MIO, oleic acid+linoleic acid+gamma-linolenic acid+alpha-linolenic acid), or palm oil (PLO, palmitic acid+oleic acid+linoleic acid) with 0.5% cholesterol for 15 wk. There were no significant differences in the food intake and body weight gain among the groups. The liver weight in the PEO and PLO groups was significantly higher than other groups. The serum total cholesterol and very low density lipoprotein (VLDL)+intermediate density lipoprotein (IDL)+low density lipoprotein (LDL)-cholesterol concentrations were consistently higher in PLO group than in the other groups. The serum high density lipoprotein cholesterol concentration was significantly lower in the PEO group than in the other groups. The liver cholesterol concentration group was significantly higher in the PEO than in the other groups. There were no significant differences in the hepatic LDL receptor mRNA level among the groups. Hepatic apo B, HMG-CoA reductase and cholesterol 7alpha-hydroxylase mRNA levels were not affected by the experimental conditions. However, hepatic cholesterol 7alpha-hydroxylase mRNA level in the PEO and MIO groups tended to be higher than in the other groups. The fecal cholesterol extraction was significantly higher in the MIO and PLO groups than in the PEO and EPO groups and the total bile acid extraction was significantly higher in the PEO and MIO groups than in the PLO group. The results of this study demonstrated that both n-6 fatty acid and n-3 fatty acids such as gamma-linolenic acid and alpha-linolenic acid lowered serum total cholesterol and VLDL+IDL+LDL-cholesterol concentrations of rats in the presence of excess cholesterol in the diet compared with dietary saturated fatty acid.     

Taurine prevents hypercholesterolemia in ovariectomized rats fed corn oil but not in those fed coconut oil

We studied whether the type of dietary fatty acid influences the preventive effect of taurine on the ovarian hormone deficiency-induced increase in plasma cholesterol concentration in 6-mo-old ovariectomized rats. Rats were fed one of the following four diets for 28 d: purified diets based on corn oil, which is rich in linoleic acid, with or with out taurine (50 g/kg) or purified diets based on coconut oil, which is rich in lauric and myristic acids, with or without taurine. Body mass gain, food intake, liver weight and plasma apolipoprotein (apo) A-I, apo B, LDL and VLDL concentrations were not affected by the diets. On the other hand, taurine lowered the plasma total cholesterol concentration (P < 0.02) in rats fed corn oil, but not in those fed coconut oil. In rats fed both types of oils, taurine increased the LDL receptor mRNA level (P < 0.01), hepatic cholesterol 7alpha-hydroxylase activity (P < 0.01) and fecal bile acid excretion (P < 0.01). Taurine increased the HMG-CoA reductase mRNA level (P < 0.02) in the liver of rats fed coconut oil, but not in those fed corn oil. Taurine increased liver total lipid (P < 0.05) and triglyceride (P < 0.05) concentrations in rats fed corn oil, but not in those fed coconut oil. These results indicate that the effect of taurine on ovarian hormone deficiency-induced changes in cholesterol metabolism is influenced by the type of dietary fatty acids.     

The hypocholesterolemic effect of high amylose cornstarch in rats is mediated by an enlarged bile acid pool and increased fecal bile acid excretion,not by cecal fermented products

Sham-operated and cecectomized rats were fed for 21 d a cholesterol-free purified diet containing (200 g/kg) either normal cornstarch (CS) or high amylose cornstarch (HACS). In both types of rats, those fed the HACS diet had a significantly lower plasma total cholesterol concentration and a significantly larger intestinal bile acid pool than those fed the CS diet. In cecectomized rats, those fed the HACS diet had significantly lower plasma HDL and LDL cholesterol concentrations, a significantly greater fecal bile acid excretion and a significantly lower hepatic 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase mRNA concentration than those fed the CS diet. The plasma triglyceride concentration and LDL-receptor mRNA concentration were not affected by the diet or cecectomy. In sham-operated rats, the propionate concentration in the cecal contents was significantly greater in those fed the HACS diet than in those fed the CS diet. Compared with sham-operated rats, cecectomized rats had significantly enhanced cholesterol 7alpha-hydroxylase activity. In intact rats, biliary bile acid flux into the small intestine was significantly greater in those fed the HACS diet than in those fed the CS diet. Thus, the hypocholesterolemic effect of HACS appears to be mediated by accelerated fecal excretion of bile acids and increases in the intestinal pool and biliary flux of bile acids, and not by cecal fermentation products.     

The cholesterolaemic effects of dietary fats in cholesteryl ester transfer protein transgenic mice.

In order to investigate the role of cholesteryl ester transfer protein (CETP) in the cholesterolaemic response to dietary fats, we analysed plasma lipid profiles of CETP-transgenic and control C57BL/6 mice fed standard chow (AIN-93G; AIN), a low-fat diet, and diets high in butter (saturated fatty acids; SFA), high-oleic acid safflower oil (monounsaturated fatty acids; MUFA), and safflower oil (polyunsaturated fatty acids; PUFA) for 5 weeks. Each group contained four or five mice. There were significant diet and dietxgenotype effects on plasma total cholesterol (TC; and respectively), liver TC ( and respectively), and esterified cholesterol (EC; and respectively); diet effects on plasma triacylglycerol liver free cholesterol and body weight a genotype effect on body-weight gain and a dietxgenotype effect on energy intake In transgenic mice the SFA diet caused significantly higher plasma TC than the PUFA diet In control mice MUFA and PUFA diets, but not the SFA diet, caused significantly higher plasma TC than the low-fat and AIN diets Transgenic mice fed PUFA had lower plasma TC while transgenic mice fed MUFA had lower LDL+VLDL-cholesterol than controls in the same dietary groups. Transgenic mice fed MUFA and PUFA diets also had significantly higher liver TC and respectively) and EC and respectively) than controls fed the same diets. In the present study we showed that: (1) CETP transgenic mice had a cholesterolaemic response to dietary fats similar to that in human subjects; (2) CETP transgenic mice fed PUFA showed significantly lower plasma TC, while those fed MUFA had lower LDL+VLDL-cholesterol than controls; (3) hepatic accumulation of cholesterol, possibly resulting from the combination of the enhanced cholesteryl ester transfer to apolipoprotein B-containing lipoproteins and increased hepatic uptake of cholesterol, may contribute to the cholesterol-lowering effect of MUFA and PUFA in CETP-transgenic mice; (4) CETP may play a role in appetite and/or energy regulation.     

复合膳食纤维对大鼠脂代谢的短期作用

目的：　通过研究复合膳食纤维（ Ｄ Ｆ Ｃ） 对大鼠脂代谢的影响,以寻求降脂效果良好的最佳 Ｄ Ｆ Ｃ 比例配方,为进一步研究 Ｄ Ｆ Ｃ 可能的作用和机理提供依据。方法：　雌性、断乳 Ｓ Ｄ 大鼠４２ 只,经高脂饲料诱导成高脂血症模型后,按体重和血清总胆固醇水平均衡的原则分为６ 组,分别给予总膳食纤维水平一致但比例构成不同的四种复合膳食纤维,以高脂饲料作为对照组,观察其对大鼠血浆和肝脏脂质、粪中胆汁酸含量的影响。结果：　１ ．四种复合膳食纤维对大鼠摄食及生长发育均无不良影响。２ ．可溶性纤维（ Ｓ Ｄ Ｆ） 与不可溶性纤维（ Ｉ Ｓ Ｄ Ｆ） 比例为４ ．４ ,２ ．０ 及１ ．０ 的三种 Ｄ Ｆ Ｃ 均能显著降低高脂血症大鼠的血胆固醇（ Ｔ Ｃ） 、低密度脂蛋白胆固醇（ Ｌ Ｄ Ｌ Ｃ） 及肝胆固醇（ Ｌ Ｃ Ｈ） 水平,且这种作用与 Ｓ Ｄ Ｆ／ Ｉ Ｓ Ｄ Ｆ 比值之间密切相关;以 Ｓ Ｄ Ｆ／ Ｉ Ｓ Ｄ Ｆ＝２ ．０ 的 Ｄ Ｆ Ｃ Ｂ 作用最佳。３ ．各 Ｄ Ｆ Ｃ 均能增高大鼠血浆高密度脂蛋白胆固醇（ Ｈ Ｄ Ｌ Ｃ） 及 Ｈ Ｄ Ｌ Ｃ 与 Ｌ Ｄ Ｌ Ｃ 的比值,仍以 Ｓ Ｄ Ｆ Ｆ／ Ｉ Ｓ Ｄ Ｆ＝ ２ ．０ 的 Ｄ Ｆ Ｃ Ｂ 作用最为显著。４ ．各组动物的粪胆汁酸排泄量高     

Docosahexaenoic acid-rich fish oil and pectin have a hypolipidemic effect, but pectin increases risk factor for colon cancer in rats

This study was designed to compare the effect of fish oil rich in DHA and pectin on the level of plasma lipids, hepatic HMG CoA reductase activity, microsomal membrane fluidity, colonic luminal content of short chain fatty acids (SCFA) and fecal excretion of bile acids and neutral sterols in rats. Male SD rats (7wks) were divided into three groups according to dietary fat sources, beef tallow (BT), corn oil (CO), fish oil (FO) and each group was subdivided into cellulose and pectin groups. The rats were fed for 25 wks the experimental diet containing 15% fat and 6% fiber and all rats were intramuscularly injected. with DMH. FO significantly reduced the levels of plasma Chol, TG, LDL-C, VLDL-C and hepatic HMG CoA reductase activity and increased membrane fluidity as compared with BT and CO. Pectin significantly reduced the levels of plasma Chol, VLDL-C and LDL-C, but increased HDL-C, HMG CoA reductase activity and membrane fluidity (p<0.05). However, pectin significantly increased the luminal content of butyrate and propionate in CO-fed rats and increased fecal excretion of deoxycholic acid and lithocholic acid in BT and CO-fed rats (p<0.05). Overall, fish oil had a protective effect against CVD by inhibiting hepatic HMG CoA reductase activity and increasing hepatic microsomal fluidity, thus leading to a reduction in plasma lipids. Pectin also had a protective effect against CVD by increasing fecal excretion of neutral sterols and hepatic microsomal fluidity. Pectin, however, increased risk factors for colon cancer by increasing the production of secondary bile acids and SCFA in the colon.     

Hypolipidemic Effects and Safety of Lactobacillus Reuteri 263 in a Hamster Model of Hyperlipidemia

We aimed to verify the beneficial effects of probiotic strain Lactobacillus reuteri 263 (Lr263) on hypolipidemic action in hamsters with hyperlipidemia induced by a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet (HCD)). Male Golden Syrian hamsters were randomly divided into two groups: normal (n = 8), standard diet (control), and experimental (n = 32), a HCD. After a two-week induction followed by a six-week supplementation with Lr263, the 32 hyperlipidemic hamsters were divided into four groups (n = 8 per group) to receive vehicle or Lr263 by oral gavage at 2.1, 4.2, or 10.5 × 10⁹ cells/kg/day for 6 weeks, designated the HCD, 1X, 2X and 5X groups, respectively. The efficacy and safety of Lr263 supplementation were evaluated by lipid profiles of serum, liver and feces and by clinical biochemistry and histopathology. HCD significantly increased serum levels of total cholesterol (TC), triacylglycerol (TG) cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C ratio, hepatic and fetal TC and TG levels, and degree of fatty liver as compared with controls. Lr263 supplementation dose dependently increased serum HDL-C level and decreased serum TC, TG, LDL-C levels, LDL-C/HDL-C ratio, hepatic TC and TG levels, and fecal TG level. In addition, Lr263 supplementation had few subchronic toxic effects. Lr263 could be a potential agent with a hypolipidemic pharmacological effect.     

Hypolipidemic Effect of Tomato Juice in Hamsters in High Cholesterol Diet-Induced Hyperlipidemia

Tomato is a globally famous food and contains several phytonutrients including lycopene, β-carotene, anthocyanin, and flavonoids. The increased temperature used to produce tomato juice, ketchup, tomato paste and canned tomato enhances the bioactive composition. We aimed to verify the beneficial effects of processed tomato juice from Kagome Ltd. (KOT) on hypolipidemic action in hamsters with hyperlipidemia induced by a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet (HCD)). Male Golden Syrian hamsters were randomly divided into two groups for treatment: normal (n = 8), standard diet (control); and experimental (n = 32), HCD. The 32 hamsters were further divided into four groups (n = 8 per group) to receive vehicle or KOT by oral gavage at 2787, 5573, or 13,934 mg/kg/day for six weeks, designated the HCD-1X, -2X and -5X groups, respectively. The efficacy and safety of KOT supplementation was evaluated by lipid profiles of serum, liver and feces and by clinical biochemistry and histopathology. HCD significantly increased serum levels of total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C ratio, hepatic and fetal TC and TG levels, and degree of fatty liver as compared with controls. KOT supplementation dose-dependently decreased serum TC, TG, LDL-C levels, LDL-C/HDL-C ratio, hepatic TC and TG levels, and fecal TG level. Our study provides experiment-based evidence to support that KOT may be useful in treating or preventing the onset of hyperlipidemia.     

The effects of high-intensity resistance exercise on the blood lipid profile and liver function in hypercholesterolemic hamsters

It is well established that atherogenic dyslipidemia, characterized by high levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein (LDL) cholesterol and low levels of high-density lipoprotein (HDL) cholesterol, constitutes important risk factors for cardiovascular disease. Regular exercise has been associated with a reduced risk for metabolic diseases. However, studies supporting the concept that resistance exercise is a modifier of blood lipid parameters are often contradictory. The aim of this study was to investigate the effects of high-intensity resistance exercise on the serum levels of TG, TC, HDL and non-HDL cholesterol, glucose, and the liver function enzymes alanine aminotransferase (ALT, EC 2.6.1.2) and aspartate aminotransferase (AST, EC 2.6.1.1) in golden Syrian hamsters (Mesocricetus auratus (Waterhouse, 1839)) fed a hypercholesterolemic diet. Sedentary groups (S) and exercise groups (E) were fed a standard diet (SS and ES) or a cholesterol-enriched diet (standard plus 1% cholesterol, SC and EC). Resistance exercise was performed by jumps in the water, carrying a load strapped to the chest, representing 10 maximum repetitions (10 RM, 30 s rest, five days per week for five weeks). Mean blood sample comparisons were made by ANOVA + Tukey or ANOVA + Kruskal-Wallis tests (p < 0.05) to compare parametric and nonparametric samples, respectively. There were no differences in blood lipids between the standard diet groups (SS and ES) (p > 0.05). However, the EC group increased the glucose, non-HDL, and TC levels in comparison with the ES group. Moreover, the EC group increased the TG levels versus the SC group (p < 0.05). In addition, the ALT levels were increased only by diet treatment. These findings indicated that high-intensity resistance exercise contributed to dyslipidemia in hamsters fed a hypercholesterolemic diet, whereas liver function enzymes did not differ in regards to the exercise protocol.     

高直链玉米淀粉对卵巢切除大鼠体内胆固醇代谢影响的研究

目的:研究高直链玉米淀粉(HACS)对因雌性激素缺乏引起的高胆固醇血症的影响。方法:将36只Wistar成年雌鼠随机分为6组,5组进行双侧卵巢切除手术(OVX),分别喂食不添加(对照)和添加10%、20%、30%、40%HACS的饲料,另1组进行卵巢伪切除手术,喂食不添加HACS的对照饲料。实验喂养4w后解剖,测定血清和肝脏中胆固醇、甘油三酯浓度、肝脏胆固醇羟化酶(CYP7)活性以及小肠、盲肠中胆汁酸总量和粪中胆汁酸排泄量等指标。结果:OVX组大鼠血浆和肝脏中胆固醇和甘油三酯浓度显著高于伪切除组大鼠。与对照饲料组相比,饲料中添加20%和30%HACS能显著降低血清中甘油三酯浓度;添加30%和40%HACS能显著降低去势大鼠血清胆固醇;添加30%和40%HACS显著增加了小肠中胆汁酸含量和粪中胆汁酸排泄量;各组间CYP7活性没有显著性差异。结论:HACS对因雌性激素缺乏引起的高胆固醇血症有明显降低效果,可能的作用机制是通过增加肠道中胆汁酸总量和粪中胆汁酸的排泄量来降低血液中胆固醇浓度。     

Plasma lipids, lipoproteins, and fecal excretion of neutral sterols and bile acids in rats fed various high fat diets or a low fat/high sucrose diet

The effect of feeding various diets on plasma lipids and lipoproteins and on fecal excretion of neutral sterols and bile acids was studied in rats fed for 7 wk diets containing 42% of energy as either coconut oil (CO), sunflower seed oil (SO), fish body oil (FBO), cod liver oil (CLO), or a low fat/high sucrose diet (SU). Triacylglycerols (TG) in whole plasma and VLDL + LDL were lower in rats fed high amounts of polyunsaturated fatty acids (PUFA) than in those fed the CO diet. Plasma HDL2 components in FBO and CLO groups were generally lower than in the other groups. Percentages of liver and heart linoleic and arachidonic acid were higher in the SO group, but lower in groups fed marine oils, than in the CO group. There was a high relative amount of eicosapentaenoic and docosahexaenoic acid in liver and heart of rats fed marine oils. Fecal excretion of bile acids was lower in the PUFA groups than in the CO group, whereas the sum of neutral sterols was similar in all groups. Plasma HDL2 (and VLDL + LDL) correlated positively, but HDL3 negatively, with fecal bile acid excretion. Accordingly, increased bile acid excretion does not seem to account for hypolipemia following intake of PUFA diets.     

Effect of dietary ascorbic acid, cholesterol and PCB on cholesterol and bile acid metabolism in a rat mutant unable to synthesize ascorbic acid

The effect of acute or chronic ascorbic acid deficiency on the activity of hepatic cholesterol 7 alpha-hydroxylase and fecal excretion of bile acids was investigated in ODS-od/od (OD) rats (a rat mutant unable to synthesize ascorbic acid) fed a purified basal diet or purified diets containing either cholesterol (2%) or polychlorinated biphenyl (PCB) (200 mg/kg). In OD rats, the dietary requirement of ascorbic acid to maintain normal growth and normal levels of cholesterol in serum and liver is about 300 mg of ascorbic acid/kg diet. In OD rats fed the basal diet, acute or chronic ascorbic acid deficiency did not affect the activity of hepatic cholesterol 7 alpha-hydroxylase and fecal excretion of bile acids. However, in OD rats fed diets containing either cholesterol or PCB, acute ascorbic acid deficiency caused a higher level of serum cholesterol, a lower activity of hepatic cholesterol 7 alpha-hydroxylase and a lower excretion of fecal bile acids than in OD rats fed a basal diet containing an adequate level of ascrobic acid. It is concluded that acute ascorbic acid deficiency causes a hypercholesterolemia due to the depression of bile acid synthesis in OD rats fed a purified diet with cholesterol or PCB.     

Chinese soft-shelled turtle egg powder lowers serum cholesterol, increases faecal neutral steroids and bile acid excretion, and up-regulates liver cytochrome P450 mRNA level in rats

The aim of the present study was to investigate the effect of Chinese soft-shelled turtle whole egg powder (TE) on cholesterol metabolism in Sprague-Dawley rats to determine whether it has a cholesterol-lowering effect. Forty male Sprague-Dawley rats were fed a high-fat diet supplemented with TE (0, 0.75, 1.50 or 3.00 g/kg body weight) administrated by gavage for 24 weeks. Serum total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C) and faecal total bile acids levels were determined by enzymatic methods. Faecal steroid concentrations were measured by GC. Means and standard deviations were calculated where appropriate for values, and the data were tested by one-way ANOVA. After 24 weeks of feeding a high-fat diet with TE supplementation, serum TC and LDL-C levels, liver cholesterol and liver lipid levels were reduced in rats. TE supplementation did not affect the faecal output, but significantly increased steroid concentrations in faeces, indicating increased steroids excretion. The faecal bile acid excretion was also increased as evidence by elevated mRNA level of liver cytochrome P450, family 7, subfamily A, polypeptide 1. Our results demonstrated that the TE does have a cholesterol-lowering effect by increasing the excretion of total bile acids and neutral steroids.     

番茄红素预防脂代谢紊乱的作用及机制探讨

目的探讨番茄红素预防高脂喂饲大鼠脂代谢紊乱的作用及机制。方法用高脂饲料喂养大鼠,同时,给予番茄红素灌胃,检测血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、肝重、肝指数、脂蛋白脂酶(LPL)和肝脂酶(HL)活性;用蛋白印迹法测定低密度脂蛋白受体(LDL-R)的表达,探讨番茄红素预防高脂血症的可能机制。结果番茄红素各剂量组的血TC、TG、LDL-C肝重及肝指数显著减轻,有效地提高了LPL和HL活性,其中,高剂量组明显。同时,番茄红素可增加LDL-R的表达。结论番茄红素具有预防高脂喂饲大鼠肝组织脂代谢紊乱的作用。其机制可能是通过提高LRL和HL活性,增加LDL-R的表达,减少甘油三酯(TG)和低密度脂蛋白(LDL)在肝组织中的蓄积,从而预防肝组织脂代谢的紊乱。     

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.     

Effect of cholestyramine in early weaning on later response to serum and fecal steroid levels and cholesterol 7 alpha-hydroxylase activity to high-cholesterol diet in ExHC rats

Male ExHC (exogenous hypercholesterolemic) rats were either prematurely weaned at 17 days of age or allowed to nurse until 35 days of age. The prematurely weaned rats were either fed a diet containing cholestyramine or cholestyramine-free diet until 35 days of age. Cholestyramine supplementation markedly increased fecal bile acid excretion and modified the composition. After giving a stock diet for 7 weeks, all rats received a cholesterol-enriched diet for 9 weeks. The serum cholesterol level in later time was not affected by early dietary manipulation. The activity of hepatic cholesterol 7 alpha-hydroxylase and fecal bile acid excretion at the end of the cholesterol challenge decreased in the cholestyramine-pretreated group, when compared to the normally weaned group. Fecal excretion and the ratio of the secondary (deoxycholic and lithocholic acids) to the primary (cholic and chenodeoxycholic acids) bile acids significantly decreased in the early cholestyramine-treated group. These results suggest that a modification of bile acid metabolism in early life may strongly influence the hepatic and possibly colonic bile acid metabolism in later life, when challenged with a high-cholesterol diet.