| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Dietary cholesterol absorption; more than just bile Lu, K., M. H. Lee, et al. (2001), Trends Endocrinol Metab 12(7): 314-20. Abstract: Absorption of dietary cholesterol from the intestine is an important part of cholesterol homeostasis and represents the first step that allows dietary cholesterol to exert its metabolic effects. Although the role of bile salts in the initial absorption of dietary cholesterol, by the formation of emulsions, is readily appreciated, the recognition that other molecular mechanisms might govern this process is only recently gaining momentum. Not only does the intestine regulate the amount of dietary cholesterol that enters the body; it is very selective with regard to the sterols that are allowed in. The human intestine is responsible for absorbing a significant amount of cholesterol each day. In addition to approximately 0.5 g d(-1) of dietary cholesterol, many other sterols are also present in almost equal abundance in the normal diet. Approximately 0.4 g of plant sterols, such as sitosterol, brassicasterol and avanesterol, are also present. However, the human body seems to allow only cholesterol to enter and remain in the body, with almost negligible amounts of plant sterols being retained. That specific molecular mechanisms are responsible for this behavior is supported by the identification of the genetic defect(s) in a rare disorder, beta-sitosterolemia (MIM 210250), where this process is disrupted. Such studies are now beginning to throw light on sterol absorption and excretion and elucidate the molecular mechanisms that govern these processes. |
| Dietary cholesterol affects Na+-K+ pump function in rabbit cardiac myocytes Gray, D. F., P. S. Hansen, et al. (1997), Am J Physiol 272(4 Pt 2): H1680-9. Abstract: Alterations in membrane cholesterol induced in vitro can alter Na+-K+ pump function. Because dietary cholesterol can influence membrane cholesterol in vivo, we examined if dietary cholesterol is a determinant of Na+-K+ pump function. Rabbits were fed cholesterol-supplemented diets for 1-4 wk. Cardiac myocytes were then isolated, and Na+-K+ pump currents (Ip) were measured using the whole cell patch-clamp technique. When the Na+ concentration in the patch pipettes (Napip) was 10 mM, a modest diet-induced increase in serum cholesterol was associated with stimulation of Ip; large increases in serum cholesterol were associated with inhibition. There was no effect of modest or large increases in serum cholesterol on Ip when Napip was 80 mM. The Napip-Ip relationship determined using seven different levels of Napip from 0 to 80 mM indicated that a modest increase in serum cholesterol increased the apparent affinity of the pump for cytoplasmic Na+. In contrast, dietary cholesterol had no effect on the apparent affinity of the pump for extracellular K+. We conclude that cholesterol intake influences the sarcolemmal Na+-K+ pump. This may have clinical implications for cardiovascular function. |
| Dietary cholesterol affects serum lipids, lipoproteins and LDL metabolism in cynomolgus monkeys in a dose-dependent manner Stucchi, A. F., R. J. Nicolosi, et al. (1998), J Nutr 128(7): 1104-13. Abstract: To examine the mechanism(s) underlying the cholesterolemic response to dietary cholesterol and saturated fatty acids, low density lipoprotein (LDL) metabolism was studied in two groups of cynomolgus monkeys fed diets containing 30 or 36% of total energy as fat. At each dietary fat level, the same group of monkeys was sequentially fed three dietary cholesterol concentrations as egg yolk in the following sequence: low (0.01 mg/kJ), medium (0.03 mg/kJ) and high (0.05 mg/kJ) for 30, 32 and 24 wk, respectively. Dietary polyunsaturated and monounsaturated fatty acids were the same in the two groups; the 6% difference in fat was due to the saturated fatty acids, 12:0 and 14:0. Serum total cholesterol, LDL cholesterol and LDL apolipoprotein B concentrations increased (P < 0.05) with dietary cholesterol in a dose-dependent manner in both fat groups. These elevations were the result of generally increasing LDL apolipoprotein B production rates, concomitant with reduced LDL apolipoprotein B fractional clearance at the high cholesterol intake. Serum HDL cholesterol and HDL apolipoprotein A-I concentrations were not affected in a consistent manner. These results demonstrate that cynomolgus monkeys are hyperresponsive to dietary cholesterol compared with humans, suggesting that this model may be useful in identifying metabolic and genetic predictors for hyperresponsiveness to dietary cholesterol in humans as well as assessing the metabolic heterogeneity of responses to dietary cholesterol. |
| Dietary cholesterol affects sympathetic nerve function in rabbit hearts Luo, T. Y., C. C. Wu, et al. (2004), J Biomed Sci 11(3): 339-45. Abstract: In order to assess the effect of hypercholesterolemia on cardiac sympathetic nerve function, New Zealand white rabbits were fed a normal diet (the control group) or one enriched with 0.5% cholesterol the hypercholesterol (HC) group for 3 months. Before and after the 3-month diet treatment, we performed serial imaging examinations and analyzed the uptake and washout ratio of (123)I-meta-iodobenzylguanidine ((123)I-MIBG) from the myocardium by administration of (123)I-MIBG through an ear vein. At the end of the experiments, the rabbits were sacrificed, and right ventricular strips were taken from their hearts. The inotropic response of the right ventricular strips to isoproterenol (ISO) and norepinephrine (NE) were evaluated. The cardiac MIBG uptake of the HC group, which was evaluated using the heart to mediastinum ratio, was higher than that of the age-matched control group. However, the washout ratios of (123)I-MIBG did not differ statistically between the two groups. On pretreatment with cocaine, NE-enhanced contractility was greater in papillary muscles isolated from the HC group. The concentration-response curve to ISO was shifted to the right in the HC group, compared with that in the control group. In conclusion, hypercholesterolemia in rabbits resulted in an increase in sympathetic nerve density in the myocardium, a decrease in the inotropic response to ISO and an increase in the inotropic response to NE in cocaine-treated myocardium. Both the in vivo and in vitro studies demonstrated the functional significance of neural remodeling induced by hypercholesterolemia. |
| Dietary cholesterol alters Na+/K+ selectivity at intracellular Na+/K+ pump sites in cardiac myocytes Buhagiar, K. A., P. S. Hansen, et al. (2004), Am J Physiol Cell Physiol 286(2): C398-405. Abstract: A modest diet-induced increase in serum cholesterol in rabbits increases the sensitivity of the sarcolemmal Na+/K+ pump to intracellular Na+, whereas a large increase in cholesterol levels decreases the sensitivity to Na+. To examine the mechanisms, we isolated cardiac myocytes from controls and from rabbits with diet-induced increases in serum cholesterol. The myocytes were voltage clamped with the use of patch pipettes that contained osmotically balanced solutions with Na+ in a concentration of 10 mM and K+ in concentrations (K+pip) ranging from 0 to 140 mM. There was no effect of dietary cholesterol on electrogenic Na+/K+ current (Ip) when pipette solutions were K+ free. A modest increase in serum cholesterol caused a K+pip-dependent increase in Ip, whereas a large increase caused a K+pip-dependent decrease in Ip. Modeling suggested that pump stimulation with a modest increase in serum cholesterol can be explained by a decrease in the microscopic association constant KK describing the backward reaction E1 + 2K+ --> E2(K+)2, whereas pump inhibition with a large increase in serum cholesterol can be explained by an increase in KK. Because hypercholesterolemia upregulates angiotensin II receptors and because angiotensin II regulates the Na+/K+ pump in cardiac myocytes in a K+pip-dependent manner, we blocked angiotensin synthesis or angiotensin II receptors in vivo in cholesterol-fed rabbits. This abolished cholesterol-induced pump inhibition. Because the epsilon-isoform of protein kinase C (epsilonPKC) mediates effects of angiotensin II on the pump, we included specific epsilonPKC-blocking peptide in patch pipette filling solutions. The peptide reversed cholesterol-induced pump inhibition. |
| Dietary cholesterol and atherosclerosis McNamara, D. J. (2000), Biochim Biophys Acta 1529(1-3): 310-20. Abstract: The perceived relationship between dietary cholesterol, plasma cholesterol and atherosclerosis is based on three lines of evidence: animal feeding studies, epidemiological surveys, and clinical trials. Over the past quarter century studies investigating the relationship between dietary cholesterol and atherosclerosis have raised questions regarding the contribution of dietary cholesterol to heart disease risk and the validity of dietary cholesterol restrictions based on these lines of evidence. Animal feeding studies have shown that for most species large doses of cholesterol are necessary to induce hypercholesterolemia and atherosclerosis, while for other species even small cholesterol intakes induce hypercholesterolemia. The species-to-species variability in the plasma cholesterol response to dietary cholesterol, and the distinctly different plasma lipoprotein profiles of most animal models make extrapolation of the data from animal feeding studies to human health extremely complicated and difficult to interpret. Epidemiological surveys often report positive relationships between cholesterol intakes and cardiovascular disease based on simple regression analyses; however, when multiple regression analyses account for the colinearity of dietary cholesterol and saturated fat calories, there is a null relationship between dietary cholesterol and coronary heart disease morbidity and mortality. An additional complication of epidemiological survey data is that dietary patterns high in animal products are often low in grains, fruits and vegetables which can contribute to increased risk of atherosclerosis. Clinical feeding studies show that a 100 mg/day change in dietary cholesterol will on average change the plasma total cholesterol level by 2.2-2.5 mg/dl, with a 1.9 mg/dl change in low density lipoprotein (LDL) cholesterol and a 0.4 mg/dl change in high density lipoprotein (HDL) cholesterol. Data indicate that dietary cholesterol has little effect on the plasma LDL:HDL ratio. Analysis of the available epidemiological and clinical data indicates that for the general population, dietary cholesterol makes no significant contribution to atherosclerosis and risk of cardiovascular disease. |
| Dietary cholesterol and coronary heart disease Connor, W. E. and S. L. Connor (2002), Curr Atheroscler Rep 4(6): 425-32. Abstract: Dietary cholesterol has been known as a dominant factor in the genesis of atherosclerosis since 1908. The evidence for the role of dietary cholesterol is based upon animal experiments, the chemistry of atherosclerotic plaques, worldwide epidemiology, and human feeding studies. All lines of evidence converge to indicate that dietary cholesterol is a major factor in promoting the growth of the atherosclerotic plaque by increasing its cholesterol content. Confusion about dietary cholesterol has arisen because amounts above a certain quantity (the ceiling) do not elevate plasma cholesterol and low-density lipoprotein cholesterol. The therapeutic threshold for dietary cholesterol is below 100 mg/d. |
| Dietary cholesterol and downregulation of cholesterol 7 alpha-hydroxylase and cholesterol absorption in African green monkeys Rudel, L., C. Deckelman, et al. (1994), J Clin Invest 93(6): 2463-72. Abstract: In this study, hepatic production of bile acid was considered together with intestinal cholesterol absorption as potential regulatory sites responsive to dietary cholesterol. Sequential liver biopsies were taken from 45 feral African green monkeys studied during three different diet periods. Low-fat Monkey Chow was fed during the baseline period, a cholesterol and fat-enriched diet was then fed for 12 wk during period 2, and finally, after a washout period of 10 wk, three subgroups were fed low-, moderate-, and high-cholesterol diets for 12 mo during period 3. The percentage of cholesterol absorbed in the intestine was significantly lower when higher levels of cholesterol were fed; however, this percentage was significantly and positively correlated to plasma cholesterol concentration at each dietary cholesterol level. Hepatic free and esterified cholesterol content were significantly elevated by dietary cholesterol challenge and remained elevated even after 20 wk of low-cholesterol diets. Hepatic mRNA abundance for cholesterol 7 alpha-hydroxylase (C7H) was significantly lower (approximately 60%) when the high-cholesterol diet was fed, with the decrease being greater than that seen for low density lipoprotein (LDL) receptor mRNA. At the same time, hepatic mRNA abundance for apolipoprotein B and hepatic lipase were not diet sensitive. C7H activity was decreased to a similar extent by diet as was C7H mRNA, although the correlation between enzyme activity and mRNA abundance was only r = 0.5, suggesting that dietary regulation includes factors in addition to transcriptional regulation. Activity and mRNA abundance of C7H remained decreased when liver esterified cholesterol content was reduced to only a two- to three-fold elevation over baseline, at a time when plasma cholesterol and hepatic LDL receptor mRNA abundance had returned to baseline levels. These data on liver C7H, obtained in one of the few primate species predisposed to cholesterol gallstone formation, support the hypothesis that the liver may attempt to downregulate intestinal cholesterol absorption by decreasing bile acid production when increased amounts of absorbed dietary cholesterol reach the liver. Presumably this represents attempted downregulation of intestinal cholesterol absorption by limiting bile acid availability as a means to maintain hepatic cholesterol balance. |
| Dietary cholesterol and fat saturation effects on plasma esterified and unesterified cholesterol in selected lines of Japanese quail females Siegel, H. S., S. M. Hammad, et al. (1995), Poult Sci 74(8): 1370-80. Abstract: Three lines of Japanese quail females, randombred controls (CL), high response (HL), and low response (LL) lines, selected for plasma total cholesterol for 18 generations, were fed all-plant-source, nonatherogenic diets to which 0 or.5% cholesterol were added from 6 to 18 wk of age. In all three lines, plasma cholesterol increased when cholesterol was fed; however, responses were greater in the HL than in the LL line, with CL intermediate. In a second experiment, females of the three lines were fed, from 6 to 14 wk of age, four isocaloric, isonitrogenous plant-source diets to which were added: 1) 10% glucose monohydrate (cerelose); 2) 10% cerelose +.1% cholesterol; 3) 4% corn oil; or 4) 4% coconut oil. Baseline data obtained before feeding experimental diets indicated that the HL had significantly higher plasma total, esterified (EC) and unesterified (UEC) cholesterol than LL and that nonovulating females had higher concentrations of esterified cholesterol than ovulating females. Diets used did not affect cholesterol fractions in the ovulating females, although there were significant differences among lines. Dietary cholesterol significantly increased the ratio of EC to UEC. Sclerotic lesion scores were higher in the HL than the LL birds and in birds fed the coconut oil diet. |
| Dietary cholesterol and incidence of lung cancer: the Western Electric Study Shekelle, R. B., A. H. Rossof, et al. (1991), Am J Epidemiol 134(5): 480-4; discussion 543-4. Abstract: The hypothesis that dietary cholesterol is positively associated with lung cancer was investigated in a 24-year cohort study of 1,878 middle-aged men who were employed in 1958 by the Western Electric Company in Chicago. The relative risk of lung cancer associated with an increment in dietary cholesterol of 500 mg/day was 1.9 (95 percent confidence interval 1.1-3.4) after adjustment for cigarettes, age, and intake of beta-carotene and fat. Results suggested that the association was specific to cholesterol from eggs. Further research is needed to understand the basis for this association. |
| Dietary cholesterol and plasma lipoproteins Nestel, P. J. (1993), Ann N Y Acad Sci 676: 1-10. |
| Dietary cholesterol and the activity of stearoyl CoA desaturase in rats: evidence for an indirect regulatory effect Landau, J. M., A. Sekowski, et al. (1997), Biochim Biophys Acta 1345(3): 349-57. Abstract: The effect of cholesterol on stearoyl CoA desaturase (SCD) was investigated. Previous work had shown that the addition of cholesterol to the diet of rats produced higher liver SCD activity compared to non-cholesterol-fed controls. We have confirmed this result and investigated the mechanism responsible for this cholesterol-induced higher SCD activity. Rats were fed either a 10% corn oil (CO) or a 10% corn oil/1% cholesterol (CO/CH) diet for 1, 3, or 7 days. SCD mRNA abundance was 3.3, 1.9, and 2.4 times greater in livers from CO/CH-fed animals after 1, 3, and 7 days, respectively. Northern hybridization of RNA from kidney, intestinal mucosa, heart, adipose, and liver demonstrated that cholesterol feeding specifically altered liver SCD mRNA. Liver esterified cholesterol content increased 27-fold with cholesterol feeding. This esterified cholesterol increase was accompanied by a proportionately greater increase in oleic acid compared to other fatty acids. These studies indicate that cholesterol does influence the expression of SCD specifically in the liver and suggest that the product, oleic acid, is preferentially esterified to cholesterol in the liver. Preliminary liver nuclear run-on assays from rats fed CO or CO/CH diets for 1 and 3 days indicate that transcription regulation is not a factor. |
| Dietary cholesterol and the optimal diet for reducing risk of atherosclerosis McNamara, D. J. (1995), Can J Cardiol 11 Suppl G: 123G-126G. Abstract: The importance of dietary cholesterol in the incidence of hypercholesterolemia in the population remains a topic of scientific debate. Analysis of the results from over 30 years of cholesterol feeding studies (n = 128) in more than 2750 patients indicate that for the majority of individuals modest changes in dietary cholesterol have little if any effect on plasma lipoprotein cholesterol levels. Data demonstrate that on average a change in cholesterol intake of 100 mg/day results in a change in plasma total cholesterol of 0.07 mmol/L (2.5 mg/dL). The studies also show that the extent of response to dietary cholesterol is independent of the amount of dietary fat and of the baseline plasma cholesterol level. In contrast, the dose adjusted plasma cholesterol response to a dietary cholesterol challenge is affected by the type of dietary fat and the baseline dietary cholesterol intake. Based on these data a reduction in dietary cholesterol intake from 450 to 300 mg/day will, on average, lower plasma cholesterol levels by 0.10 mmol/L (3.7 mg/dL). This decrease is modest and highly variable due to significant interindividual heterogeneity of responses. It is estimated that one-third of the population is sensitive to dietary cholesterol whereas two-thirds are resistant to plasma cholesterol changes. In comparison, a 1% decrease in energy intake from saturated fat decreases plasma cholesterol 0.08 mmol/L (3 mg/dL). Consumption of products marketed as 'No cholesterol' with high total and saturated fat clearly does not contribute to the optimal diet for reducing plasma cholesterol levels of risk of atherosclerosis. |
| Dietary cholesterol and the origin of cholesterol in the brain of developing rats Edmond, J., R. A. Korsak, et al. (1991), J Nutr 121(9): 1323-30. Abstract: Milk substitutes containing cholesterol at concentrations lower, equal to or greater than the concentrations found in natural rat milk were fed to artificially reared rat pups from 5 d until 15 or 16 d after birth. Pups reared by their mother served as controls. In one experiment, D7-cholesterol was fed in the milk at four different concentrations. The purpose of the study was to determine whether cholesterol in milk influenced growth and the sterol composition of brain over the period of its most rapid accumulation in this organ. We found that body and brain weights were not different, irrespective of the concentration of cholesterol in the milk substitutes. High concentrations of cholesterol in milk caused a significant increase in cholesterol in liver and plasma, whereas the concentration of cholesterol in brain was not different from the concentration in the brain of controls. The amounts of D7-cholesterol in lung and liver, and in plasma and RBC that pass the brain, were consistent with the concentration fed in the milk and approached 70% of the total content of cholesterol in these organs at the highest concentration fed. Brain, by contrast, contained very small amounts of D7-cholesterol, which could readily be attributed to D7-cholesterol associated with the vascular system of the blood-brain barrier. We found that the sterol composition of brain is not influenced by the concentration of cholesterol in milk and that cholesterol exogenous to brain, even in a hypercholesterolemic condition, does not gain entry to the brain. We conclude that the brain biosynthesizes de novo all the cholesterol it requires. |
| Dietary cholesterol and type of fat differentially affect cholesterol metabolism and atherosclerosis in baboons Mott, G. E., E. M. Jackson, et al. (1992), J Nutr 122(7): 1397-406. Abstract: This study was designed to determine the differences in cholesterol metabolism due to dietary cholesterol and type of fat in adult baboons. From weaning at 16 wk to 7-8 y of age, 80 baboons were fed one of four diets: high cholesterol (0.24 mg/kJ) or low cholesterol (0.0024 mg/kJ) with 40% of energy from saturated fat polyunsaturated/saturated fatty acid ratio (P/S) = 0.37 or unsaturated fat (P/S = 2.1). High cholesterol and saturated fat independently raised serum lipoprotein and apolipoprotein concentrations to about the same extent. The liver cholesterol concentration of baboons fed high cholesterol diets was 23% higher than that of baboons fed low cholesterol. High dietary cholesterol also increased bile cholesterol concentration by 25%, the neutral steroid excretion rate by 66% and the bile acid excretion rate by 30%. With feeding of saturated fat, compared with unsaturated fat, liver cholesterol was 24% lower, bile cholesterol 26% lower and the neutral steroid excretion rate 12% lower. Dietary cholesterol greatly suppressed whole-body cholesterol synthesis, but type of fat did not affect cholesterol synthesis rate. These results suggest that dietary cholesterol and saturated fat increase plasma lipoprotein concentrations through different physiological mechanisms. |
| Dietary cholesterol as a conditioner of ingestion of other nutrients and various blood parameters in young women Ortega, R. M., M. E. Quintas, et al. (1998), Nutr Hosp 13(5): 221-7. Abstract: The aim of the study was to determine the effects of cholesterol intakes of greater (HC) or less than 300 mg/day (LC) (the upper advisable limit for the control of cholesterolaemia and the risk of cardiovascular disease) on a range of blood parameters, and to determine any influence such intakes might have on the consumption of food, energy and nutrients. The study subjects we one hundred and thirty young women. Food intake was determined using a 7-day dietary record (including a Sunday). A range of serum lipid parameters, and haematological and biochemical indicators of iron status were also determined. The percentage discrepancy between observed energy intake and theoretical energy expenditure was greater amongst LC subjects (9.7 +/- 18.8% compared to 5.5 +/- 24.4% in HC subjects) (P < 0.05). Analysis of covariance was therefore performed with respect to the degree of underestimation/overestimation of intake. The comparison of the adjusted means showed that HC subjects consumed greater quantities of eggs and meat and less alcohol, than did LC subjects. HC subjects also showed greater intakes of protein, carbohydrates, total fats, monounsaturated fatty acids, polyunsaturated fatty acids, saturated fatty acids, cholesterol, riboflavin, niacin, folic acid, vitamin E, zinc and iron. At blood level, HC subjects showed greater quantities of red blood cells, haemoglobin and HDL cholesterol. No significant differences were seen between LC and HC subjects for the remaining blood and biochemical parameters investigated. The development of criteria for the greatest protection against cardiovascular disease whilst maintaining good nutritive condition, is the subject of studies soon to be commenced. Women may need different advice to men, owing to their greater need of iron. Greater quantities of foods rich in haem iron, such as meat and fish, might be appropriate for the female population. |
| Dietary cholesterol does not increase biomarkers for chronic disease in a pediatric population from northern Mexico Ballesteros, M. N., R. M. Cabrera, et al. (2004), Am J Clin Nutr 80(4): 855-61. Abstract: BACKGROUND: An increased incidence of coronary artery disease (CAD) is prevalent in northern Mexico. Effects of specific dietary components on risk factors for CAD have not been evaluated in children. OBJECTIVE: The purpose was to evaluate the effects of dietary cholesterol provided by whole eggs on the lipoprotein profile, LDL size, and phenotype in children from this region. DESIGN: Children (29 girls and 25 boys aged 8-12 y) were randomly assigned to either 2 eggs/d (EGG period; 518 additional mg cholesterol) or the equivalent amount of egg whites (SUB period; 0 additional mg cholesterol) for 30 d. After a 3-wk washout period, the children were assigned to the alternate treatment. RESULTS: Subjects were classified as hyporesponders (no increase or /=0.06 mmol/L increase). During the EGG period, the hyperresponders (n = 18) had an elevation in both LDL cholesterol (from 1.54 +/- 0.38 to 1.93 +/- 0.36 mmol/L) and HDL cholesterol (from 1.23 +/- 0.26 to 1.35 +/- 0.29 mmol/L) with no changes in LDL:HDL. In contrast, hyporesponders (n = 36) had no significant alterations in plasma LDL or HDL cholesterol. All subjects had an increase in LDL peak diameter during the EGG period (P < 0.01) and a decrease (P < 0.01) in the smaller LDL subfractions. In addition, 5 of the children having LDL phenotype B (15%) shifted from this high-risk pattern to pattern A after the EGG treatment. CONCLUSIONS: Intake of 2 eggs/d results in the maintenance of LDL:HDL and in the generation of a less atherogenic LDL in this population of Mexican children. |
| Dietary cholesterol does not normalize low plasma cholesterol levels but induces hyperbilirubinemia and hypercholanemia in Mdr2 P-glycoprotein-deficient mice Voshol, P. J., N. R. Koopen, et al. (2001), J Hepatol 34(2): 202-9. Abstract: BACKGROUND/AIMS: Mdr2 P-glycoprotein deficiency in mice (Mdr2(-/-) leads to formation of cholesterol/cholesterol-depleted bile and reduced plasma HDL cholesterol. We addressed the questions: (1) does HDL in Mdr2(-/-) mice normalize upon phospholipid and/or cholesterol feeding, and (2): is the Mdr2(-/-) liver capable of handling excess dietary cholesterol. METHODS: Male and female Mdr2(-/-) and Mdr2(+/+) mice were fed diets with or without additional phosphatidylcholine and/or cholesterol. Plasma, hepatic and biliary lipids as well as liver function parameters and expression of transport proteins involved in bile formation were analyzed. RESULTS: Feeding excess phospholipids and/or cholesterol did not affect lipoprotein levels in Mdr2(+/+) or Mdr2(-/+) mice. Dietary cholesterol caused hyperbilirubinemia (male +100%; female +500%) and elevated plasma bile salts (male +200%; female +1250%) in Mdr2(-/-) mice only, independent of phospholipids. Bile flow nor biliary bile salt and bilirubin secretion were affected in cholesterol-fed Mdr2(-/-) mice. Elevated plasma bile salts may be related to cholesterol-induced reduction of hepatic Na+-taurocholate cotransporting protein expression in Mdr2(-/-) mice. CONCLUSION: Excess dietary phospholipids and cholesterol do not normalize low HDL associated with Mdr2 P-glycoprotein-deficiency. Induction of hyperbilirubinemia and hypercholanemia by dietary cholesterol in Mdr2(-/-) mice delineates the important role of biliary lipid secretion in normal hepatic functioning. |
| Dietary cholesterol effects on plasma and yolk cholesterol fractions in selected lines of Japanese quail Hammad, S. M., H. S. Siegel, et al. (1996), Poult Sci 75(7): 933-42. Abstract: Japanese quail from lines that had been divergently selected for high (HL) or low (LL) plasma total cholesterol and their unselected control line (CL) were fed an all vegetable diet to which 0 or 0.5% crystalline cholesterol were added. Relationships between plasma and yolk cholesterol fractions were examined at 10, 14, and 18 wk of age, which followed 2, 6, and 10 wk consumption of the cholesterol-enriched diet, respectively. Unesterified cholesterol (UC) and cholesteryl esters (CE) in plasma and yolk were analyzed using HPLC. There were no consistent correlations between yolk and plasma for UC, individual CE, total esterified cholesterol (EC), or total cholesterol in the selected lines at ages tested, whether or not 0.5% cholesterol was added to the diet. Cholesterol concentrations in milligrams per gram of yolk and in milligrams per yolk were higher in the HL than the LL at 10 and 14, but not at 18 wk of age. Yolk weights of the HL females increased from 10 to 18 wk of age, whereas those of the LL did not. Cholesterol concentrations in the LL yolks continued to increase over time, however the increases in yolk weight in the HL were not accompanied by proportional increases in cholesterol deposition in the yolk, leading to a dilution of concentration of cholesterol fractions in the HL yolk. Dietary cholesterol increased egg production rate in the selected lines but did not increase the cholesterol content of the yolk. |
| Dietary cholesterol enhances impaired endothelium-dependent relaxations in aortas of salt-induced hypertensive Dahl rats Kitagawa, S., Y. Yamaguchi, et al. (1996), Eur J Pharmacol 297(1-2): 71-6. Abstract: We investigated the effect of hypercholesterolemia on the vascular reactivity of thoracic aortas isolated from hypertensive Dahl salt-sensitive (DS) rats. DS rats were fed on a low-sodium diet (control group), a low-sodium plus high-cholesterol diet (CHOL group), a high-sodium diet (NaCl group) or a high-sodium plus high-cholesterol diet (NaCl + CHOL group) for 8 weeks. Hypercholesterolemia developed in the CHOL and NaCl + CHOL groups, while hypertension developed in the NaCl and NaCl + CHOL groups, with these changes being greatest in the NaCl + CHOL group. Aortic cholesteryl ester accumulation was attenuated in the aortic rings from the NaCl and NaCl + CHOL groups, compared to the control group. The degree of attenuation in the NaCl + CHOL group was significantly greater than that in the NaCl group. Endothelium-dependent relaxations induced by the calcium ionophore A23187 were attenuated only in the NaCl + CHOL group. Endothelium-independent relaxations in response to sodium nitroprusside were slightly but significantly attenuated in the NaCl + CHOL group. The relaxations in the CHOL group were comparable to those in the control group. These findings indicate that cholesterol feeding strikingly enhances the impaired endothelium-dependent relaxations and the slightly impaired endothelium-independent relaxations in the aorta of DS rats with salt-induced hypertension, parallel to the development of hypertension, hypercholesterolemia and cholesterol deposition. |