| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Dietary cholesterol metabolism in Japanese quail lines selected for plasma cholesterol levels Hammad, S. M., H. S. Siegel, et al. (1997), Proc Soc Exp Biol Med 214(1): 62-8. Abstract: Dietary cholesterol metabolism was studied, using a single dose of emulsion, per os (test meal), in lines of Japanese quail that were divergently selected for high (HL) and low (LL) plasma total cholesterol. The meal contained 3H cholesterol, 14C beta-sitosterol, unlabeled cholesterol, triolein, and bile salt. Recovery of the nonabsorbable beta-sitosterol in the excreta permitted determination of the percentage of cholesterol absorbed. The amounts of 3H in the plasma, egg yolks, and the excreta neutral and acid sterols were determined. A line-x-time interaction for 3H in plasma indicated that the level of plasma cholesterol derived from the test meal declined more rapidly in the LL than in the HL. The higher 3H detected in the excreta acidic sterols of the LL 12 hr after the test meal indicated that bile acid excretion of cholesterol was greater in the LL than in the HL. There were no differences in cholesterol absorption between lines or sexes. Cumulative 3H radioactivity in the eggs over 18 days following the test meal was higher in the HL yolks; however, this line effect was due to the greater number of eggs produced by the HL. Thus, one of the mechanisms by which the LL maintains low plasma cholesterol levels is by an enhanced excretion of bile acid compared with the HL. The data also suggest that the more severe atherogenic effect of dietary cholesterol observed in the HL could be, in part, due to the longer residence time of cholesterol in circulation. |
| Dietary cholesterol modifies pyroglutamyl aminopeptidase activity in mouse frontal cortex. Sexual differences Ramirez Exposito, M. J., M. J. Garcia, et al. (2001), Rev Neurol 32(10): 904-7. Abstract: INTRODUCTION: Pyroglutamyl aminopeptidase (pGluAP) is an omega peptidase widely distributed in fluid and tissues, which hydrolyses biological active peptides including thyrotropin-releasing-hormone (TRH). In the last years, different endocrine and extraendocrine functions have been attributed to TRH. OBJECTIVES: The aim of present work is to study the influence of high dietary cholesterol on soluble and membrane bound pGluAP activity in frontal cortex of male and female mice. Material and methods. Soluble and membrane bound pGluAP activities of frontal cortex of mice feeding during 15 days, a standard diet enriched with cholesterol (1%) and cholic acid (0.5%) were measured using fluorimetric assays. RESULTS: Significant increases were observed in membrane bound pGluAP activity in males and females. No changes were detected in soluble pGluAP activity in frontal cortex of females but a significant increase was observed in this enzymatic activity in males. CONCLUSIONS: High dietary cholesterol induces a significant increase in tissue pGluAP activity. These increases may produce changes in TRH metabolism which may be related with alterations in its neuromodulatory functions and with the possible relationship between TRH and other neurotransmitter systems. |
| Dietary cholesterol modulates delta6 and delta9 desaturase mRNAs and enzymatic activity in rats fed a low-eFA diet Brenner, R. R., A. M. Bernasconi, et al. (2002), Lipids 37(4): 375-83. Abstract: The effects of a 1% addition of cholesterol to a diet low in EFA on FA desaturases were examined. The administration of cholesterol markedly increased the esterified cholesterol content in microsomes and total liver lipids from the first day, whereas the proportion of free cholesterol remained unaltered throughout the treatment. An excellent homeostasis in the free cholesterol content was apparently evoked by the acyl-CoA cholesterol acyltransferase. The cholesterol esters were mainly oleate, palmitate, and stearate, and the addition of cholesterol increased the relative proportions of cholesterol palmitoleate and oleate. The addition of cholesterol to a low-EFA diet induced, as in animals fed a high-EFA diet, a marked increase in liver stearoyl-CoA desaturase-1 mRNA and enzyme activity. This increased activity apparently evoked a similar enhancement of palmitoleic and oleic acids in total and microsomal liver lipids. The cholesterol-rich diet depressed the liver A6 and delta5 desaturase activity. However, the abundance of delta6 desaturase mRNA was not modified throughout the treatment. This indicates that the depressive effect is evoked at a step beyond that controlled by the mRNA level. The depression of both enzymatic activities was consistent with the decrease in the percentages of arachidonic acid and DHA in total and microsomal liver lipids. Taken together, these results indicate that through its modulating effect on the desaturases, dietary cholesterol may lead an animal or human fed low-EFA diet to a true deficiency by the decreased synthesis of the highly polyunsaturated acids derived from linoleic and alpha-linolenic acids. |
| Dietary cholesterol opposes PUFA-mediated repression of the stearoyl-CoA desaturase-1 gene by SREBP-1 independent mechanism Kim, H. J., M. Miyazaki, et al. (2002), J Lipid Res 43(10): 1750-7. Abstract: Stearoyl-CoA desaturase (SCD) catalyzes the rate-limiting step in the cellular synthesis of monounsaturated fatty acids, mainly oleate (18:1) and palmitoleate (16:1), which are the major monounsaturated fatty acids of membrane phospholipids, cholesteryl esters, waxes, and triglycerides. The mouse expresses three well-characterized SCD genes (SCD1, 2, and 3). SCD1 is the main isoform expressed in the liver of mice. Previous in vivo studies have shown that the transcriptional repression by n-3 and n-6 polyunsaturated fatty acids (PUFAs) and the induction by cholesterol of the SCD1 gene are dependent on the maturation of the sterol regulatory element-binding protein-1c (SREBP-1c). We studied the regulation of SREBP-1, SCD1, and other SREBP-1 target genes when a high cholesterol diet is combined with PUFA as n-6 PUFA rich soybean oil (SO), or n-3 PUFA rich fish oil (FO). While the PUFA/cholesterol (PUFA/CH) diets repressed the maturation of the SREBP-1, the SCD1 mRNA levels, and protein and enzyme activity were induced. Compared with PUFA diets, hepatic cholesterol ester and triglyceride were enriched with 16:1 and 18:1 monounsaturated fatty acids in mice fed PUFA/CH diets. Total plasma cholesterol levels were not altered but plasma triglycerides were reduced in SO/CH-fed mice compared with SO-fed mice. The mRNA for SREBP-1 was increased by the PUFA/CH diet but the mRNA levels of SREBP-1 target genes such as fatty acid synthase and LDL receptor were decreased, indicating that the main control of PUFA-mediated suppression of SREBP-1 target genes is the maturation of SREBP-1. This study demonstrates that cholesterol overrides the PUFA-mediated repression of the SCD1 gene and regulates SCD1 gene expression through a mechanism independent of SREBP-1 maturation. |
| Dietary cholesterol reduces lipoprotein lipase activity in the atherosclerosis-susceptible Bio F(1)B hamster McAteer, M. A., D. C. Grimsditch, et al. (2003), Br J Nutr 89(3): 341-50. Abstract: We have compared lipoprotein metabolism in, and susceptibility to atherosclerosis of, two strains of male Golden Syrian hamster, the Bio F(1)B hybrid and the dominant spot normal inbred (DSNI) strain. When fed a normal low-fat diet containing approximately 40 g fat and 0.3 g cholesterol/kg, triacylglycerol-rich lipoprotein (chylomicron+VLDL) and HDL-cholesterol were significantly higher (P<0.001) in Bio F(1)B hamsters than DSNI hamsters. When this diet was supplemented with 150 g coconut oil and either 0.5 or 5.0 g cholesterol/kg, significant differences were seen in response. In particular, the high-cholesterol diet produced significantly greater increases in plasma cholesterol and triacylglycerol in the Bio F(1)B compared with the DSNI animals (P=0.002 and P<0.001 for cholesterol and triacylglycerol, respectively). This was particularly dramatic in non-fasting animals, suggesting an accumulation of chylomicrons. In a second experiment, animals were fed 150 g coconut oil/kg and 5.0 g cholesterol/kg for 6 and 12 months. Again, the Bio F(1)B animals showed dramatic increases in plasma cholesterol and triacylglycerol, and this was confirmed as primarily due to a rise in chylomicron concentration. Post-heparin lipoprotein lipase activity was significantly reduced (P<0.001) in the Bio F(1)B compared with the DSNI animals at 6 months, and virtually absent at 12 months. Bio F(1)B animals were also shown to develop significantly more (P<0.001) atherosclerosis. These results indicate that, in the Bio F(1)B hybrid hamster, cholesterol feeding reduces lipoprotein lipase activity, thereby causing the accumulation of chylomicrons that may be associated with their increased susceptibility to atherosclerosis. |
| Dietary cholesterol regulates hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase gene expression in rats primarily at the level of translation Chambers, C. M. and G. C. Ness (1998), Arch Biochem Biophys 354(2): 317-22. Abstract: The level of gene expression at which dietary cholesterol exerts feedback regulation on hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was investigated using young male Sprague-Dawley rats. Previous studies suggested that this regulation might be exerted posttranscriptionally. Thus, possible regulation at the levels of catalytic efficiency, protein turnover, and translation was investigated. To examine possible regulation at the level of catalytic efficiency, rats were placed on chow diets supplemented with 2% cholesterol and the rates of decline in hepatic HMG-CoA reductase activity and immunoreactive protein levels were determined. Both decreased slowly over a 72-h period. The catalytic efficiency did not change. These observations are inconsistent with phosphorylation-dephosphorylation or thiol-disulfide interchange as possible mechanisms. The possibility that dietary cholesterol might act by increasing the rate of turnover of HMG-CoA reductase protein was examined by determining the half-life of the enzyme in livers from rats consuming chow or chow supplemented with 2% cholesterol. The half-life of HMG-CoA reductase protein was not decreased in the animals receiving cholesterol, thus ruling out this possibility. Regulation at the level of translation was investigated by measuring the rate of HMG-CoA reductase protein synthesis in liver slices using 35Smethionine and 35Scysteine. It was found that the rate of synthesis was reduced by over 80% in liver slices from rats fed a diet supplemented with 2% cholesterol. Similar results were obtained with liver slices from rats given mevalonolactone, which supplies both sterol and nonsterol endproducts. These results indicate that cholesterol regulates hepatic HMG-CoA reductase gene expression in rats primarily at the level of translation. |
| Dietary cholesterol stimulates CYP7A1 in rats because farnesoid X receptor is not activated Xu, G., L. X. Pan, et al. (2004), Am J Physiol Gastrointest Liver Physiol 286(5): G730-5. Abstract: Cholesterol feeding upregulates CYP7A1 in rats but downregulates CYP7A1 in rabbits. To clarify the mechanism responsible for the upregulation of CYP7A1 in cholesterol-fed rats, the effects of dietary cholesterol (Ch) and cholic acid (CA) on the activation of the nuclear receptors, liver X-receptor (LXR-alpha) and farsenoid X-receptor (FXR), which positively and negatively regulate CYP7A1, were investigated in rats. Studies were carried out in four groups (n = 12/group) of male Sprague-Dawley rats fed regular chow (control), 2% Ch, 2% Ch + 1% CA, and 1% CA alone for 1 wk. Changes in mRNA expression of short heterodimer partner (SHP) and bile salt export pump (BSEP), target genes for FXR, were determined to indicate FXR activation, whereas the expression of ABCA1 and lipoprotein lipase (LPL), target genes for LXR-alpha, reflected activation. CYP7A1 mRNA and activity increased twofold and 70%, respectively, in rats fed Ch alone when the bile acid pool size was stable but decreased 43 and 49%, respectively, after CA was added to the Ch diet, which expanded the bile acid pool 3.4-fold. SHP and BSEP mRNA levels did not change after feeding Ch but increased 88 and 37% in rats fed Ch + CA. This indicated that FXR was activated by the expanded bile acid pool. When Ch or Ch + CA were fed, hepatic concentrations of oxysterols, ligands for LXR-alpha increased to activate LXR-alpha, as evidenced by increased mRNA levels of ABCA1 and LPL. Feeding CA alone enlarged the bile acid pool threefold and increased the expression of both SHP and BSEP. These results suggest that LXR-alpha was activated in rats fed both Ch or Ch + CA, whereas CYP7A1 mRNA and activity were induced only in Ch-fed rats where the bile acid pool was not enlarged such that FXR was not activated. In rats fed Ch + CA, the bile acid pool expanded, which activated FXR to offset the stimulatory effects of LXR-alpha on CYP7A1. |
| Dietary cholesterol stimulates hepatic biosynthesis of triglyceride and reduces oxidation of fatty acids in the rat Fungwe, T. V., L. M. Cagen, et al. (1993), J Lipid Res 34(6): 933-41. Abstract: Experiments were conducted in the intact rat and in the isolated, perfused rat liver to investigate the possibility that the increase in the concentration of hepatic triglyceride and increase in the secretion of the very low density lipoprotein (VLDL)-triglyceride (TG) resulting from addition of cholesterol to the diet are due to stimulation of synthesis of triglyceride, reduced fatty acid oxidation, or both. Male rats were fed for 7 days with either a cholesterol-free diet to which 5% (w/w) corn oil was added, or with the same diet supplemented with 0.5% cholesterol. Fed animals received 1-14Coleic acid via the tail vein, as a complex with rat serum, and were killed 2 h later. Feeding cholesterol for 7 days increased hepatic triglyceride and cholesteryl ester (CE) concentrations, moderately elevated free cholesterol, but did not affect phospholipid (PL) levels, as we had previously observed after a feeding period of 3 weeks. Incorporation of 1-14Coleic acid into hepatic and plasma triglyceride increased significantly (60 and 48%, respectively) with cholesterol feeding. Incorporation of 1-14Coleic acid into hepatic and plasma cholesteryl esters increased by 63 and 79%, respectively, while incorporation into phospholipid was unaffected. Increasing the fat (corn oil) content of the diet to 20% (w/w) did not change these effects of dietary cholesterol. Studies using isolated, perfused rat livers were carried out in vitro after rats were fed the 5% corn oil diet for 3 weeks. Perfusions lasted 4 h. The perfusion medium contained 3% bovine serum albumin and 30% washed bovine erythrocytes in Krebs-Henseleit-HCO3 buffer.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Dietary cholesterol supplementation improves growth and behavioral response of pigs selected for genetically high and low serum cholesterol Schoknecht, P. A., S. Ebner, et al. (1994), J Nutr 124(2): 305-14. Abstract: We hypothesized that, in pigs selected for low (L) or high (H) serum cholesterol for four generations, neonatal endogenous cholesterol synthesis would be sufficient to meet requirements for brain and body growth. In Experiment 1, eight 16-wk-old L pigs received a diet with or without 200 mg cholesterol/100 g diet for 35 d. Supplemented pigs grew approximately 25% faster and had a significantly greater concentration of free cholesterol in the cerebrum. In Experiment 2, 16 H and 16 L newborn pigs were fed a milk replacer with or without 200 mg cholesterol/100 g diet for 28 d. Pigs fed cholesterol had greater average daily gain (P < or = 0.09), significantly reduced liver 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity, and significantly increased cerebral cholesterol content than pigs not fed cholesterol. One of three indices of exploratory behavior was significantly greater in the L pigs that received cholesterol compared with L pigs that did not receive cholesterol. These data suggest that these neonatal pigs are unable to produce sufficient cholesterol to meet requirements for normal growth and brain development and are dependent on dietary cholesterol in milk. |
| Dietary cholesterol supplementation in the spontaneously diabetic rat Veiga, P. A., J. B. Van Liew, et al. (1995), Life Sci 56(9): 697-700. Abstract: Dietary cholesterol supplementation was used to increase serum cholesterol concentration in diabetic and non-diabetic rats. With the use of numerous dietary formulations, extremely elevated serum cholesterol concentrations and gastrointestinal intolerance were found. We conclude that there are unacceptable side effects with a vast number of exogenous cholesterol supplemented diets which preclude standard and long-term usage. |
| Dietary cholesterol withdrawal reduces vascular inflammation and induces coronary plaque stabilization in miniature pigs Verhamme, P., R. Quarck, et al. (2002), Cardiovasc Res 56(1): 135-44. Abstract: OBJECTIVE: To study the effect of dietary cholesterol withdrawal on size and composition of LDL-hypercholesterolemia-induced coronary plaques in miniature pigs. METHODS: Pigs were on normal chow (control group), on a cholesterol-rich diet for 37 weeks (hypercholesterolemic group) or on a cholesterol-rich diet followed by normal chow for 26 weeks (cholesterol withdrawal group). Endothelial function was assessed with quantitative angiography after intracoronary infusion of acetylcholine, plaque load with intra-coronary ultrasound and plaque composition with image analysis of cross-sections. The effect of porcine serum on coronary smooth muscle cell (SMC) function was studied in vitro. RESULTS: Cholesterol-rich diet caused LDL-hypercholesterolemia, increased plasma levels of oxidized LDL (ox-LDL) and C-reactive protein (CRP), and induced endothelial dysfunction and coronary atherosclerosis. Dietary cholesterol withdrawal lowered LDL, ox-LDL and CRP. It restored endothelial function, did not affect plaque size but decreased lipid, ox-LDL and macrophage content. Smooth muscle cells and collagen accumulated within the plaque. Increased smoothelin-to-alpha-smooth muscle actin ratio indicated a more differentiated SMC phenotype. Cholesterol lowering reduced proliferation and apoptosis. In vitro, hypercholesterolemic serum increased SMC apoptosis and decreased SMC migration compared to non-hypercholesterolemic serum. CONCLUSIONS: Cholesterol lowering induced coronary plaque stabilization as evidenced by a decrease in lipids, ox-LDL, macrophages, apoptosis and cell proliferation, and an increase in differentiated SMC and collagen. Increased migration and decreased apoptosis of SMC may contribute to the disappearance of the a-cellular core after lipid lowering. |
| Dietary cholesterol, cholesterol absorption, postprandial lipemia and atherosclerosis Huff, M. W. (2003), Can J Clin Pharmacol 10 Suppl A: 26A-32A. Abstract: The relationship among dietary cholesterol, cholesterol absorption, the metabolism of cholesterol-rich chylomicron remnants and atherosclerosis is complex; however, recent advances have provided insight into the mechanisms involved. Although dietary cholesterol is an independent risk factor for atherosclerosis, the attributable risk is low compared with dietary variables such as the amount and type of fat. Clinical studies have demonstrated that in humans consuming a typical Western-type diet, decreasing the amount of dietary cholesterol intake results in only small changes in low-density lipoprotein (LDL)-cholesterol and little or no change in the ratio of total cholesterol to high-density lipoprotein cholesterol. These findings are better appreciated when all sources of cholesterol entering the intestinal lumen are considered. Only a third of intestinal cholesterol per day is derived from the diet. Cholesterol from endogenous sources, including the bile and intestinal epithelial cells, represents the majority of cholesterol absorbed and subsequently formed into chylomicrons and secreted into the circulation. There is increasing evidence that postprandial lipoproteins are atherogenic, in particular, cholesterol-rich chylomicron remnants. These lipoproteins have the capacity to enter the arterial wall and promote atherogenesis at several stages of development, including the induction of smooth muscle cells and macrophage foam cell formation. Furthermore, enhanced delivery of chylomicron remnants to the liver decreases hepatic LDL-receptor expression, resulting in increased plasma LDL concentrations. Therefore, the inhibition of cholesterol absorption has become an attractive therapeutic target. There is growing genetic and biochemical evidence that intestinal cholesterol absorption is carrier-mediated, which has facilitated the development and characterization of small molecule inhibitors of this process. Ezetimibe, the first of these new compounds, inhibits intestinal absorption of dietary and biliary cholesterol and lowers total and LDL-cholesterol concentrations in plasma. By inhibiting cholesterol absorption, and possibly by reducing the cholesterol content of chylomicrons, ezetimibe may decrease the atherogenic potential of chylomicron remnants. |
| Dietary cholesterol, fat, and lung cancer incidence among older women: the Iowa Women's Health Study (United States) Wu, Y., W. Zheng, et al. (1994), Cancer Causes Control 5(5): 395-400. Abstract: To test the hypothesis that a high intake of dietary cholesterol and fat is associated with elevated risks of lung cancer, we analyzed data from a population-based, prospective, cohort study conducted among 41,837 postmenopausal Iowa (United States) women who completed, in 1986, a comprehensive mailed questionnaire including information on usual intake of 127 food items. All cohort members were followed for cancer incidence through the statewide cancer registry. By 1991, after six years of follow-up, 272 incident lung-cancer cases were identified. After controlling for total energy intake and other confounding factors, dietary cholesterol, total fat, and animal fat were unrelated to lung cancer risk. Intake in the upper three quartiles of plant-derived fat, however, was related to a 30 to 40 percent lower incidence of lung cancer, comparative with those in the lowest quartile, with more pronounced reduction in risk observed among smokers (relative risk = 0.6, 95 percent confidence interval = 0.4-0.9). This prospective cohort study suggests that high intake of fat of plant origin may be associated with reduced risk of lung cancer, while dietary cholesterol and animal fat intake is unrelated to the etiology of this malignancy in postmenopausal women. |
| Dietary cholesterol, fatty acids, and the risk of lung cancer among men Knekt, P., R. Seppanen, et al. (1991), Nutr Cancer 16(3-4): 267-75. Abstract: The relation between dietary cholesterol and fatty acids and the incidence of lung cancer was studied among 4,538 Finnish men aged 20-69 years and initially free of cancer. During 20 years of follow-up, 117 lung cancer cases were diagnosed. Cholesterol intake was not associated with lung cancer risk, the age-, smoking-, and energy-adjusted relative risk between the lowest and highest tertiles being 1.0 95% confidence interval (CI) = 0.6-1.9. The intake of saturated fatty acids was nonsignificantly related with lung cancer incidence, the relative risk for the lowest compared with the highest tertile being 1.6 (CI = 0.8-3.2). The association was stronger among smokers than among nonsmokers, the relative risks being 2.1 (CI = 1.0-4.3) and 1.3 (CI = 0.4-4.1), respectively. The relative risk among smokers, however, decreased to 1.5 after adjustment for the amount they smoked. In the total cohort, there was a significantly elevated risk of lung cancer among men with a high intake of butter, one of the main sources of saturated fatty acids, the relative risk being 1.9 (CI = 1.1-3.2). The present data do not confirm previous results suggesting that dietary cholesterol predicts the occurrence of lung cancer among men. The association between intake of saturated fatty acids and lung cancer observed in the present study may be partly due to heavy smoking among high consumers of saturated fat. |
| Dietary cholesterol, membrane cholesterol and cholesterol synthesis Lutton, C. (1991), Biochimie 73(10): 1327-34. Abstract: After describing the main steps of cholesterol biosynthesis the author recalls that the cholesterogenesis rate is feedback-inhibited by dietary cholesterol and examines the various processes of modulation. Hydroxy-3-methylglutaryl (HMG) CoA reductase, the key rate-limiting enzyme, is a 97 kDa endoplasmic reticulum glycoprotein, anchored 7-fold in this membrane. The N-terminal membrane-bound domain plays a fundamental role in the modulation of reductase activity. This modulation is essentially mediated by decreased gene transcription and enhanced degradation of the protein. The possible modulation by a bicyclic cascade system involving phosphorylation (inactivation) and dephosphorylation (activation) of reductase does not seem to play an essential role in vivo. Finally, recent data show that the lipid composition (C/P molar ratio) of some reticular membranes (fibroblasts, for example) can strongly modulate the activity of this ubiquitous enzyme. |
| Dietary cholesterol, serum cholesterol and destructive behavior Mann, G. V. (1994), Psychosom Med 56(6): 485. |
| Dietary cholesterol, serum cholesterol, and risks of cardiovascular and noncardiovascular diseases Stamler, J., P. Greenland, et al. (1998), Am J Clin Nutr 67(3): 488-92. |
| Dietary cholesterol-induced changes of protein kinase C and the effect of vitamin E in rabbit aortic smooth muscle cells Sirikci, O., N. K. Ozer, et al. (1996), Atherosclerosis 126(2): 253-63. Abstract: The changes occuring in smooth muscle cells during the development of atherosclerosis in rabbits fed 2% cholesterol and the effect of vitamin E treatment were investigated. Ex-vivo smooth muscle cells obtained from the aorta of cholesterol-fed rabbits exhibited a 2-fold increase of protein kinase C expression and activity. The cholesterol induced changes in protein kinase C were equally present in the membrane bound and cytosolic fraction of the enzyme. The amount of a control protein alpha-actin was not affected in smooth muscle cell by the high cholesterol diet treatment, indicating that protein kinase C increase was specific. The increase of protein kinase C expression and activity was not significantly affected by vitamin E treatment although a constant trend was noted. The data are discussed in the light of previous smooth muscle cell in vitro experiments. |
| Dietary cholesterol-induced down-regulation of intestinal 3-hydroxy-3-methylglutaryl coenzyme A reductase activity is diminished in rabbits with hyperresponse of serum cholesterol to dietary cholesterol Meijer, G. W., M. J. Smit, et al. (1993), J Nutr 123(4): 695-703. Abstract: Key enzymes of cholesterol metabolism were studied in two inbred strains of rabbits with hyper- or hyporesponse of serum cholesterol to dietary cholesterol. Baseline 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity in liver was similar in hypo- and hyperresponders, but that in intestine was twofold higher in the hyporesponders. The addition of cholesterol (3 g/kg) to the diet caused similar depression of hepatic HMG-CoA reductase activity in the two strains, whereas intestinal HMG-CoA reductase activity was significantly reduced in hyporesponders but not in hyperresponders. Cholesterol feeding induced higher free cholesterol concentrations in hepatic and intestinal microsomes of both hypo- and hyperresponders and higher activity of hepatic acyl-CoA:cholesterol acyltransferase (ACAT). Hepatic ACAT activity was significantly lower in cholesterol-fed hyperresponders than in hyporesponders, which may have contributed to the observed higher free cholesterol concentrations in hepatic microsomes of cholesterol-fed hyperresponders. Intestinal ACAT activity was similar in hypo- and hyperresponders; cholesterol feeding tended (P = 0.11) to elevate the activity of this enzyme. Hepatic cholesterol 7 alpha-hydroxylase activity was significantly higher in cholesterol-fed hyperresponders than in hyporesponders; it was slightly depressed after cholesterol loading in both rabbit strains. |
| Dietary cholesterol-induced xanthomatosis in atherosclerosis-susceptible Japanese quail (Cotunix japonica) Hoekstra, K. A., C. R. Nichols, et al. (1998), J Comp Pathol 119(4): 419-27. Abstract: Japanese quail of a strain (SUS) susceptible to dietary cholesterol-induced atherosclerosis were fed a diet supplemented with cholesterol (0.5% w/w) for 4, 8 or 12 weeks. Plasma cholesterol increased significantly from 240-1550 mg/dl at 4 weeks and remained at that concentration for 8 and 12 weeks on the same diet. Plasma triglycerides (TGs) increased from 112-384 mg/dl after 4 weeks but showed no significant increases thereafter. Striking eruptive xanthomatous lesions were noticed on the feet of 50% of these birds at 4 weeks, and the percentage of birds affected increased to 85 after 12 weeks on the cholesterol-supplemented diet. This is the first report of xanthomatosis in birds. These birds had also developed atherosclerotic plaques in the aorta and brachiocephalic arteries by 4 weeks. There was no significant correlation between xanthoma scores and plasma cholesterol and TG concentrations at any of the three sampling periods (4, 8 and 12 weeks of cholesterol feeding). There was, however, a significant negative correlation (r = -0.61) between xanthoma scores and atherosclerotic plaque scores at 4 weeks. The correlation became non-significant at later stages of cholesterol exposure. Similarities between mammalian and SUS Japanese quail xanthomatosis may make the SUS quail a useful model for the study of this disorder. |