| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Replacement of margarine on bread by rapeseed and olive oils: effects on plasma fatty acid composition and serum cholesterol Seppanen-Laakso, T., H. Vanhanen, et al. (1993), Ann Nutr Metab 37(4): 161-74. Abstract: The effects of zero erucic acid rapeseed oil and olive oil on plasma fatty acid composition and serum cholesterol were studied in margarine users (n = 46). The replacement of margarine on bread by these oils accounted, on average, for 16% of the total fat and 7% of the total energy intake. Fatty acid analysis of total plasma indicated a dose-dependent rise in alpha-linolenic (alpha-LLA) and oleic acid (OA) levels during rapeseed and olive oil substitutions, respectively. Rapeseed oil substitution increased the proportion of eicosapentaenoic acid (0.4%- units, on average) in plasma phospholipids. A slight decrease in low-density lipoprotein cholesterol (LDL-C) and an increase in high-density lipoprotein cholesterol (HDL-C, 4.5%, p < 0.01) led to a significantly higher HDL-C/total cholesterol (TC) ratio (1.9%-units). The results suggest a marked competitive effect for alpha-LLA, not only among plasma phospholipid fatty acids, but also in the relationships with serum lipids, since the changes in alpha-LLA, rather than in OA, were associated with those in LDL-C and the HDL-C/TC ratio. No competitive action of polyunsaturated acids comparable to rapeseed oil was found during olive oil substitution. In contrast to the rapeseed oil diet, the reduced proportion of linoleic acid (LA) in plasma phospholipids was not restored; this may be unfavorable if the habitual intake of LA is low. However, the effects on LDL-C levels were beneficial: the concentration decreased by 5.9% (p < 0.01), correlating inversely with the increase in OA. In addition, the concentration of HDL-C remained unchanged during olive oil substitution. |
| Replacing 40% of dietary animal fat with vegetable oil is associated with lower HDL cholesterol and higher cholesterol ester transfer protein in cynomolgus monkeys fed sufficient linoleic acid Gupta, S. V., N. Yamada, et al. (2003), J Nutr 133(8): 2600-6. Abstract: This study was designed to evaluate whether replacing approximately 40 g/100 g dietary animal fat with vegetable oil would improve plasma lipids and lipoproteins when diets contained prudent levels of total saturated acid (SFA), monounsaturated acid (MUFA) and PUFA. Using a cross-over design, male Cynomolgus monkeys (n = 10) were fed purified diets containing a mixture of fats. For the diet based on animal fat (AF-diet), approximately 85 g/100 g of the total fat was derived from pork fat, and approximately 40 g/100 g of this was replaced with olive oil for the vegetable oil-based diet (VO-diet). Thus, the fat content of the VO diet comprised 50% pork fat and 35% olive oil. The remaining 15% of the total fat (for both diets) was safflower oil. Both diets provided approximately 30% of total energy (%en) from fat, <10%en SFA and approximately 6-7%en from PUFA. Monkeys were rotated through two 7-wk feeding periods, during which time plasma lipids and lipoproteins were evaluated. Compared with the AF diet, plasma total cholesterol (TC) concentrations tended to be lower (approximately 10%) after monkeys consumed the VO diet (3.18 +/- 0.83 vs. 3.52 +/- 0.93 mmol/L, P = 0.099), and this was due entirely to a significant 12% reduction in HDL cholesterol (1.53 +/- 0.41 vs. 1.73 +/- 0.47, mmol/L, P = 0.0009). Although plasma lipoprotein compositional analyses revealed no significant differences in either lipoprotein composition or the estimated particle diameters, the measurement of cholesterol ester transfer protein (CETP) using (3)H-cholesterol ester-labeled HDL revealed that the lower HDL cholesterol (HDL-C) when monkeys consumed the VO diet was associated with a 31% increase in transfer (P = 0.04). However, despite the changes in HDL-C, the TC/HDL-C ratio did not differ between monkeys after the two diet treatments. Regression analyses of data from these monkeys revealed a significant correlation between the dietary 16:0/18:2 ratio and plasma HDL-C. These data suggest that within the context of currently recommended prudent diets, it may be possible to manipulate HDL-C beneficially. Whether a similar effect would occur in humans warrants investigation. |
| Replacing cows' with sheep's dairy fat lowers plasma cholesterol concentration in participants consuming dairy fat-rich diets Skeaff, C. M., K. Williscroft, et al. (2004), Eur J Clin Nutr 58(2): 250-7. Abstract: OBJECTIVE: To determine the effects on plasma cholesterol concentration of replacing cows' dairy fat with sheep's dairy fat. DESIGN: Randomised crossover dietary intervention. SETTING: General community, Dunedin, New Zealand. SUBJECTS: Volunteer sample of 41 healthy adults with initial plasma cholesterol concentration between 4.8 and 7.8 mmol/l. INTERVENTIONS: Participants were asked to follow a self-selected low-fat background diet throughout the study to which, during each of the 2, 3-week dairy diets, they were asked to add sheep's or cows' dairy products. MAIN OUTCOME MEASURES: Energy and nutrient intakes, plasma triacylglycerol fatty acids, and plasma cholesterol. RESULTS: Energy and nutrient intakes on the sheep-dairy and cow-dairy diets were very similar, with total, saturated, monounsaturated and polyunsaturated fat contributing 34, 18-19, 9, and 3% of total energy intake, respectively. Participants consumed approximately 50 g/day of dairy fat on each diet. Replacing cows' with sheep's dairy fat led to a 0.33 (0.11-0.56, 95% CI) mmol/l decrease (6%) in plasma total cholesterol concentration, from 5.53 (0.90, s.d.) to 5.20 (0.90) mmol/l. Plasma low-density lipoprotein (LDL) cholesterol was 0.18 (0.02-0.33) mmol/l lower on the sheep-dairy diet as was the concentration of plasma high-density lipoprotein (HDL) cholesterol, 0.11 (0.02-0.20) mmol/l. The LDL to HDL cholesterol ratio at the end of the sheep-dairy diet, 2.91 (1.10), was not significantly different (P>0.05) from the cow-dairy diet, 2.73 (0.83). CONCLUSIONS: Within the context of a diet high in dairy fat (50 g/day), replacing cows' milk fat with sheep's milk fat leads to a small reduction in plasma cholesterol concentration, but no change in the ratio of LDL to HDL cholesterol. |
| Replacing saturated fat with PUFA-rich (sunflower oil) or MUFA-rich (rapeseed, olive and high-oleic sunflower oil) fats resulted in comparable hypocholesterolemic effects in cholesterol-fed hamsters Trautwein, E. A., D. Rieckhoff, et al. (1999), Ann Nutr Metab 43(3): 159-72. Abstract: Recent studies have suggested that monounsaturated fatty acid (MUFA)-rich dietary fats do not have the same plasma cholesterol-lowering effects whereby rapeseed oil was more effective than olive oil. This phenomenon could be explicable by the content of other fatty acids or plant sterols. To further evaluate the effects of different MUFA-rich oils (18:1-rich sunflower oil, rapeseed oil, olive oil) in comparison to polyunsaturated (PUFA)-rich oils (18:2-rich sunflower oil) and saturated fat (palm stearin) on cholesterol and bile acid metabolism, male Syrian golden hamsters were fed semipurified diets containing 5% fat and 0.2% cholesterol for 5 weeks. To test whether oil refining would have an impact on the cholesterol-lowering potential, unrefined and refined varieties of rapeseed and olive oil were included. After 5 weeks, plasma total cholesterol (TC) was highest with palm stearin (10.0 +/- 2.6 mmol/l) while the MUFA- or PUFA-rich fats significantly lowered TC. The lowest TC concentrations were found with refined rapeseed, cold pressed rapeseed and 18:2-rich sunflower oil (6.7 +/- 1.2; 7.1 +/- 0.7 and 7.1 +/- 0.7 mmol/l, respectively), whereas TC was 10-15% higher (not significant) with 18:1-rich sunflower, virgin and refined olive oil. Liver cholesterol concentrations were lowest in hamsters fed palm stearin or 18:2-rich sunflower oil while MUFA-rich fats increased hepatic cholesteryl ester accumulation, especially of cholesteryl oleate. There were no significant differences in the fecal neutral sterol and bile acid excretion. These data demonstrate that MUFA-rich dietary fats, e.g. rapeseed, olive and 18:1-rich sunflower oil, are comparable in their hypocholesterolemic potential and cause similar effects on plasma cholesterol as 18:2-rich sunflower oil in hamsters when the dietary cholesterol intake is moderate. |
| Report of the Conference on Low Blood Cholesterol: Mortality Associations Jacobs, D., H. Blackburn, et al. (1992), Circulation 86(3): 1046-60. Abstract: BACKGROUND. A National Heart, Lung, and Blood Institute (NHLBI) Conference was held October 9-10, 1990, to review and discuss existing data on U-shaped relations found between mortality rates and blood total cholesterol levels (TC) in some but not other studies. Presentations were given from 19 cohort studies from the United States, Europe, Israel, and Japan. A representative of each study presented its findings and also submitted tables of proportional hazards regression coefficients for entry TC levels in regard to death, and these were incorporated into a formal statistical overview adjusted for age, diastolic blood pressure, cigarette smoking, body mass index, and alcohol intake, as available. METHODS AND RESULTS. The U-shape for total mortality in men and the flat relation in women resulted largely from a positive relation of TC with coronary heart disease death and an inverse relation with deaths caused by some cancers (e.g., lung but not colon), respiratory disease, digestive disease, trauma, and residual deaths. Risk for combined noncardiovascular, noncancer causes of death decreased steadily across the range of TC. The conference considered possible explanations for the statistical associations found between low TC levels or active TC lowering and certain causes of death. One is that TC is lowered by some disease conditions themselves, such as wasting in chronic pulmonary disease or reduced production and secretion of cholesterol-bearing lipoproteins with liver disease. In this sort of situation, the TC:mortality association found in observational studies may be due to preexisting disease. This was addressed by excluding early deaths from the analysis, which did not change the results. The conference considered as well the biological function of cholesterol, which, if seriously deranged, might hypothetically cause a wide variety of diseases and dysfunction. The conference also considered the biological functions that might provide plausible mechanisms for the associations found. CONCLUSIONS. Definitive interpretation of the associations observed was not possible, although most participants considered it likely that many of the statistical associations of low or lowered TC level are explainable by confounding in one form or another. The conference focused on the apparent existence and nature of these associations and on the need to understand their source rather than on any pertinence of the findings for public health policy. Further research is recommended to explain the observed associations of low TC levels (and TC lowering) with certain noncardiovascular diseases. This includes studies of the time course of TC change in disease, the relation of TC to morbidity, further studies of possible epidemiological confounding, monitoring of population trends in TC and mortality, further studies of the relations in women, auditing of noncardiovascular events in trials, studies of cell membrane, genetic and molecular links to cholesterol metabolism, TC level and disease, studies of disease manifestations in specific lipid disorders, and further study of the proposed causal mechanisms linking low TC and hemorrhagic stroke. |
| Report of the Expert Panel on Population Strategies for Blood Cholesterol Reduction. A statement from the National Cholesterol Education Program, National Heart, Lung, and Blood Institute, National Institutes of Health Carleton, R. A., J. Dwyer, et al. (1991), Circulation 83(6): 2154-232. |
| Report on cholesterol in Spanish children and adolescents Lorenzo, J. G. (1992), Rev Esp Cardiol 45(9): 611. |
| Report on cholesterol levels of Spanish children and adolescents. Group of Experts of Spanish Societies of Arteriosclerosis, Cardiology, Pediatrics, Nutrition and Preventive Medicine Plaza Perez, I. (1991), Rev Esp Cardiol 44(9): 567-85. Abstract: The epidemiological association between blood cholesterol levels and the development of clinical complications of arteriosclerosis, particularly coronary heart disease, is presently well established. The importance of measuring blood cholesterol levels in children and adolescents is supported by numerous evidences: beginning of arteriosclerosis in infancy, relationship between the extent of fatty streaks as determined by post mortem examination of accidentally dead children and previous blood lipid levels, aggregation in children (as in adults) of elevated blood cholesterol levels with other cardiovascular risk factors, tracking of high cholesterol levels (and of other risk factors) from childhood to adolescence and early adulthood, and association of risk factors in children with a parental history of cardiovascular disease. The few epidemiological studies of blood cholesterol in children published in Spain have demonstrated relatively high mean values of blood cholesterol at all ages, which are similar or even higher than those obtained by the LRC Program in the United States during the 1970's. The present report constitutes a metaanalysis of data provided by the authors of 21 Spanish studies, both published and unpublished, carried out during the 1980's on the blood lipid levels of children and adolescents (0-18 years-old) including a total of 19,630 subjects (10,834 males, 8,102 females, and 694 newborns). All data were obtained in cross-sectional studies of normal populations employing different biochemical and statistical methods, thus limiting the value of the conclusions on the true values of blood cholesterol in Spanish children and its changes during recent years. Weighted means were calculated for the means of the different studies taking into account the number of cases in each population, and the distribution in percentiles by age and sex of total cholesterol, triglycerides, LDLc, and HDLc were estimated. For the overall study population, the mean blood cholesterol level and the moderate risk percentile (75) and high risk percentile (95) for both sexes were 173 mg/dl (4.5 mmol/l), 200 mg/dl (5.2 mmol/l), and 225 mg/dl (5.8 mmol/l), respectively. Such levels are between 10 and 15 mg/dl (0.3 and 0.4 mmol/l) higher than those of the LRC Program, and a clear rise was observed from the early to the late 1980's. The present levels of blood cholesterol in children and adolescents have a great potential impact for Public Health policy in Spain. As it occurs in adults, the distributions of blood cholesterol levels in children of different populations reflect their coronary heart disease mortality rates.(ABSTRACT TRUNCATED AT 400 WORDS) |
| REPR and complementation factor(s) interact to modulate rat apolipoprotein B mRNA editing in response to alterations in cellular cholesterol flux Inui, Y., F. Giannoni, et al. (1994), J Lipid Res 35(8): 1477-89. Abstract: Apolipoprotein B (apoB) mRNA editing is a post-transcriptional cytidine deamination involving several protein factor(s), one of which has recently been cloned. We have examined the effects of alterations in cellular cholesterol flux in the rat liver and small intestine as a means of dissecting the physiologic mechanisms regulating apoB mRNA editing, both in vivo and in isolated S-100 extracts. Hepatic cholesteryl ester accumulation was produced by feeding rats a high cholesterol diet, alone, or in combination with either ethinyl estradiol treatment, or after induction of hypothyroidism. Endogenous hepatic apoB mRNA editing decreased in parallel with the increase in cellular cholesteryl ester content (r = -0.948, P < 0.001). None of these conditions altered endogenous intestinal apoB mRNA editing. Hepatic S-100 extracts demonstrated decreased in vitro apoB RNA editing activity, in parallel with the changes observed in vivo. By contrast, the activity of intestinal S-100 extracts demonstrated a paradoxical increase in hypothyroid rats and a similar, paradoxical decrease in hyperthyroid rats, when compared to controls. Hepatic REPR mRNA, quantitated by RNase protection assay, showed a 25-50% decrease in cholesterol-fed rats. The editing activity of hepatic S-100 extracts prepared from cholesterol-fed, hypothyroid rats was restored to control levels with REPR supplementation but not with chicken intestinal S-100 extracts, suggesting that changes in REPR, but not complementation activity, may play a critical role in the regulation of apoB mRNA editing in rat liver. By contrast, the editing activity of intestinal S-100 extracts prepared from hyperthyroid animals was unaltered by supplementation with REPR, but was restored to control levels after the addition of chicken intestinal S-100 extracts. Taken together, the data suggest that tissue-specific factors regulate apoB mRNA editing in the rat and that the complex interplay of REPR and complementation factor(s) may be modulated in response to alterations in cholesterol flux, in vivo. |
| Reproducibility of a semiquantitative food frequency questionnaire to assess the intake of fats and cholesterol in The Netherlands Feunekes, I. J., W. A. Van Staveren, et al. (1995), Int J Food Sci Nutr 46(2): 117-23. Abstract: The reproducibility of a 104 item semiquantitative food frequency questionnaire to estimate the intake of energy, fat, fatty acids and cholesterol was assessed in a group of 93 men and women in the Netherlands. The questionnaire was administered by trained interviewers. Subjects were asked to recall the consumption of 104 items during the past month. A second interview was conducted 8 weeks later. The mean difference in nutrient intake between the two assessments was very small, with a maximum of 5% for cholesterol intake, but the variance of individual differences was considerable. Pearson correlation coefficients between two assessments 8 weeks apart ranged from 0.71 for polyunsaturated fatty acids intake (when expressed as percentage of energy intake) up to 0.91 for energy intake. The reproducibility was found to be similar in males and females. Reproducibility was assessed for separate food items as well as for 20 food groups. Items consumed were often highly reproducible and rarely had a poor reproducibility. This food frequency questionnaire is considered to be a suitable tool to estimate and monitor the intake of fat, fatty acids and cholesterol in the Netherlands. |
| Reproducibility of fasting serum cholesterol and triglycerides in ambulatory patients with mixed hyperlipidemia Martina, B., M. Weinbacher, et al. (1996), Schweiz Med Wochenschr 126(50): 2175-80. Abstract: Intraindividual variability of serum lipid concentrations in normal volunteers and in patients with hyperlipidemia is substantial. The aim of this study was to investigate prospectively the reproducibility of fasting serum triglyceride and total cholesterol concentrations in primary health care patients with combined hyperlipidemia, i.e. under conditions of daily medical practice. Secondary forms of hyperlipidemia were excluded. 19 general medical outpatients with primary combined hyperlipidemia were studied. Serum total cholesterol and triglyceride concentrations were measured after an overnight fast at 08.00 h 4 times at weekly intervals. To study the influence of alcohol intake on serum lipid concentrations, total cholesterol and triglycerides were measured without alcohol influence and 12 hours after consumption of a mean of 100 g alcohol in the evening. In 19 patients (10 males, 9 females, mean age 55 years, body mass index 27.9 +/- 4.4 kg/m2), mean +/- SD of serum triglycerides was 3.97 +/- 1.8 mmol/l and of total cholesterol 7.9 +/- 1.8 mmol/l. The combined intraindividual and interassay coefficient of variation was 18.7 +/- 8.2% for triglycerides and 5.1 +/- 2.5% for total cholesterol. Fasting serum triglycerides (3.5 +/- 1.1 vs. 3.7 +/- 1.4 mmol/l) and total cholesterol (7.6 +/- 1.4 vs. 7.8 +/- 1.0 mmol/l) did not significantly change 12 hours after acute alcohol consumption. Patients with primary combined hyperlipidemia in a primary health care setting show small intraindividual variations of overnight fasted serum triglyceride and total cholesterol concentrations. Moderate alcohol consumption 12 hours before blood sampling does not significantly affect triglyceride and cholesterol values. |
| Reproducing abnormal cholesterol biosynthesis as seen in the Smith-Lemli-Opitz syndrome by inhibiting the conversion of 7-dehydrocholesterol to cholesterol in rats Xu, G., G. Salen, et al. (1995), J Clin Invest 95(1): 76-81. Abstract: The Smith-Lemli-Opitz syndrome is a recessive inherited disorder characterized by neurologic developmental defects and dysmorphic features in many organs. Recently, abnormal cholesterol biosynthesis with impaired conversion of 7-dehydrocholesterol to cholesterol has been discovered in homozygotes. To reproduce the biochemical abnormality, BM 15.766, a competitive inhibitor of 7-dehydrocholesterol-delta 7-reductase, the enzyme that catalyzes the conversion of 7-dehydrocholesterol into cholesterol was fed by gavage to rats. After 14 d, plasma cholesterol concentrations declined from 48 mg/dl to 16 mg/dl and 7-dehydro-cholesterol levels rose from trace to 17 mg/dl. Hepatocytes surrounding the central vein developed balloon necrosis. Stimulating cholesterol synthesis with cholestyramine followed by BM 15.766 produced an additional 40% decline (P < 0.05) in plasma cholesterol and 34% increase in 7-dehydrocholesterol levels compared to the inhibitor alone. Adding 2% cholesterol to the diet during the second week of BM 15.766 treatment increased plasma cholesterol threefold and decreased 7-dehydrocholesterol concentrations 55%. Hepatic 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase activity increased 73% with a 3.9-fold rise in mRNA levels but cholesterol 7 alpha-hydroxylase activity decreased slightly though mRNA levels increased 1.4 times with BM 15.766 treatment. These results demonstrate that BM 15.766 is a potent inhibitor of 7-dehydrocholesterol-delta 7-reductase. The model reproduces abnormal cholesterol biosynthesis as seen in the Smith-Lemli-Opitz syndrome and is useful to test different treatment strategies. Stimulating early steps of cholesterol synthesis worsens the biochemical abnormalities while feeding cholesterol inhibits abnormal synthesis, improves the biochemical abnormalities and prevents liver damage. |
| Reproductive, endocrine, and organ weight differences of swine selected for high or low serum cholesterol Wise, T., L. D. Young, et al. (1993), J Anim Sci 71(10): 2732-8. Abstract: Three generations of selection for 56-d blood cholesterol concentrations were used to establish low and high cholesterol lines of pigs in which cholesterol concentrations differed by 39% in the last generation. Litter size (number of fully formed pigs born per litter) diverged with each successive generation of selection and, at the third generation, litter size differed between the low and high line by two pigs (high line = 8.5 +/-.6; low line = 10.5 +/-.5; P <.05). A random selection of offspring (gilts, n = 109; boars, n = 46; barrows, n = 94) from the third generation and a control line maintained throughout the experiment were monitored for hormonal and anatomical relationships that might provide insight into the mechanisms that altered fecundity. Ovulation rate (number of corpora lutea) as determined on d 60 of pregnancy was increased in the low (n = 29) compared with the high cholesterol line (n = 38; 11.8 +/-.3 vs 9.8 +/-.3, respectively; P <.05), and litter size continued to be increased in the low cholesterol line (P <.05). No differences were noted between lines in kidney, ovarian, or total corpora lutea weight. Empty uterine weight and adrenal weight were increased in the high cholesterol line (P <.05) in randomly selected offspring of the third generation, and liver weight increased in the low line (P <.05). Associated with increased concentrations of cholesterol were increased serum concentrations of progesterone (gilts) and testosterone (boars) in the high cholesterol line (P <.05).(ABSTRACT TRUNCATED AT 250 WORDS) |
| Requirement for mevalonate in acetylated LDL induction of cholesterol esterification in macrophages Bernini, F., G. Didoni, et al. (1993), Atherosclerosis 104(1-2): 19-26. Abstract: HMG-CoA reductase inhibitors simvastatin, fluvastatin and fluvastatin enantiomers (0.1 to 5 microM) were utilized to block both mevalonate formation and cholesterol esterification in mouse peritoneal macrophages in the presence of a large excess of cholesterol supplied by acetylated LDL. Supplementation of cultures with mevalonate fully reversed, in a dose-dependent manner, the inhibitory effect of the drugs on cholesterol esterification. Mevalonate alone, in the range of the tested concentrations, did not affect cholesterol esterification in the absence of the HMG-CoA reductase inhibitors, indicating that its effect was linked to the restoration of the endogenous pool depleted by the pharmacological block of HMG-CoA reductase. The inhibitory effect of fluvastatin was also prevented by the non-sterol mevalonate isoprenoid derivative geranylgeraniol. Evaluation of fluvastatin enantiomers demonstrated the stereospecificity of drug action with most of the effect associated to the antipode with the highest inhibitory activity of HMG-CoA reductase. We conclude that mevalonate or a mevalonate product(s), possibly a non-sterol derivative(s), are required in cholesterol esterification induced by acetylated LDL in macrophages. |
| Requirement for thyroid hormone receptor beta in T3 regulation of cholesterol metabolism in mice Gullberg, H., M. Rudling, et al. (2002), Mol Endocrinol 16(8): 1767-77. Abstract: T3 potently influences cholesterol metabolism through the nuclear thyroid hormone receptor beta (TRbeta), the most abundant TR isoform in rodent liver. Here, we have tested if TRalpha1, when expressed at increased levels from its normal locus, can replace TRbeta in regulation of cholesterol metabolism. By the use of TRalpha2-/-beta-/- animals that overexpress hepatic TRalpha1 6-fold, a near normalization of the total amount of T3 binding receptors was achieved. These mice are similar to TRbeta-/- and TRalpha1-/-beta-/- mice in that they fail to regulate cholesterol 7alpha-hydroxylase expression properly, and that their serum cholesterol levels are unaffected by T3. Thus, hepatic overexpression of TRalpha1 cannot substitute for absence of TRbeta, suggesting that the TRbeta gene has a unique role in T3 regulation of cholesterol metabolism in mice. However, examination of T3 regulation of hepatic target genes revealed that dependence on TRbeta is not general: T3 regulation of type I iodothyronine deiodinase and the low density lipoprotein receptor were partially rescued by TRalpha1 overexpression. These in vivo data show that TRbeta is necessary for the effects of T3 on cholesterol metabolism. That TRalpha1 only in some instances can substitute for TRbeta indicates that T3 regulation of physiological and molecular processes in the liver occurs in an isoform-specific fashion. |
| Requirements for CEACAMs and cholesterol during murine coronavirus cell entry Thorp, E. B. and T. M. Gallagher (2004), J Virol 78(6): 2682-92. Abstract: Previous reports have documented that cholesterol supplementations increase cytopathic effects in tissue culture and also intensify in vivo pathogenicities during infection by the enveloped coronavirus murine hepatitis virus (MHV). To move toward a mechanistic understanding of these phenomena, we used growth media enriched with methyl-beta-cyclodextrin or cholesterol to reduce or elevate cellular membrane sterols, respectively. Cholesterol depletions reduced plaque development 2- to 20-fold, depending on the infecting MHV strain, while supplementations increased susceptibility 2- to 10-fold. These various cholesterol levels had no effect on the binding of viral spike (S) proteins to cellular carcinoembryonic antigen-related cell adhesion molecule (CEACAM) receptors, rather they correlated directly with S-protein-mediated membrane fusion activities. We considered whether cholesterol was indirectly involved in membrane fusion by condensing CEACAMs into "lipid raft" membrane microdomains, thereby creating opportunities for simultaneous binding of multiple S proteins that subsequently cooperate in the receptor-triggered membrane fusion process. However, the vast majority of CEACAMs were solubilized by cold Triton X-100 (TX-100), indicating their absence from lipid rafts. Furthermore, engineered CEACAMs appended to glycosylphosphatidylinositol anchors partitioned with TX-100-resistant lipid rafts, but cells bearing these raft-associated CEACAMs were not hypersensitive to MHV infection. These findings argued against the importance of cholesterol-dependent CEACAM localizations into membrane microdomains for MHV entry, instead suggesting that cholesterol had a more direct role. Indeed, we found that cholesterol was required even for those rare S-mediated fusions taking place in the absence of CEACAMs. We conclude that cholesterol is an essential membrane fusion cofactor that can act with or without CEACAMs to promote MHV entry. |
| Research note: effects of dietary fats on hepatic cholesterol synthesis in Japanese quail Hood, R. L. (1991), Poult Sci 70(8): 1848-50. Abstract: Blood lipid concentrations and hepatic cholesterol synthesis were compared in Japanese quail fed diets containing fats with different fatty acid profiles. The quail fed a diet containing tuna oil had the lowest blood cholesterol concentration; those fed beef drippings the highest, and those fed safflower oil or linseed oil had intermediate concentrations. Rates of hepatic cholesterol synthesis mirrored the results for serum cholesterol concentration. Serum triglyceride concentrations were lower in the quail fed the two diets containing n-3 fatty acids in comparison with the beef and safflower treatment groups. |
| Research profile. Cholesterol. The eye-kidney connection Kordella, T. (2002), Diabetes Forecast 55(8): 103-6. |
| Resistance exercise training is associated with decreases in serum low-density lipoprotein cholesterol levels in premenopausal women Boyden, T. W., R. W. Pamenter, et al. (1993), Arch Intern Med 153(1): 97-100. Abstract: BACKGROUND: Aerobic exercise training is associated with reduced serum concentrations of triglycerides, increased concentrations of high-density lipoprotein cholesterol, and minimal changes in serum levels of total cholesterol or low-density lipoprotein cholesterol. There are few data on the effects of resistance exercise on blood lipid levels. METHODS: Premenopausal women were randomly assigned to a supervised resistance exercise training program (n = 46) or a control group (n = 42) for 5 months. Serum was analyzed for levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides. Body composition and dietary intake were also measured. RESULTS: The exercise group showed a 0.33 +/- 0.03-mmol/L (mean +/- SE) decrease in total cholesterol level and a 0.36 +/- 0.001-mmol/L decrease in low-density lipoprotein cholesterol level that was significantly different from the control group. No significant changes were noted in serum high-density lipoprotein cholesterol or triglyceride levels in either group. Changes in body composition showed no significant correlations with changes in total cholesterol or low-density lipoprotein cholesterol. There were no significant differences in nutrient intake between the groups. CONCLUSION: In healthy, premenopausal women, with normal baseline lipid profiles, 5 months of resistance exercise training was associated with significant decreases in serum total cholesterol and low-density lipoprotein cholesterol concentrations. |
| Resistance of smooth muscle cells to assembly of high density lipoproteins with extracellular free apolipoproteins and to reduction of intracellularly accumulated cholesterol Komaba, A., Q. Li, et al. (1992), J Biol Chem 267(25): 17560-6. Abstract: Removal of intracellularly accumulated cholesterol by lipid-free human apolipoproteins (apo) A-I and A-II was studied for aortic smooth muscle cells (SMC) of rat, monkey and rabbit, human skin fibroblasts (FB), and mouse peritoneal macrophages (MP). The reaction generated high density lipoprotein (HDL)-like lipoproteins as did those and other helical apolipoproteins with MP, causing efflux of cellular cholesterol. From FB and MP, the maximum efflux rates with apoA-I and A-II per 24 h were as much as 30% of the apparent maximum efflux rate of prelabeled cellular cholesterol to human HDL. From rat SMC these rates were 7.2 and 6.8%, respectively, being independent of cellular cholesterol content. Those from monkey and rabbit SMC were also very low. When standardized for the initial cellular unesterified cholesterol pool size, the maximum efflux rates/24 h were 5.4 and 5.0% for apoA-I and A-II from rat SMC and even less from monkey and rabbit SMC in contrast to 42.4 and 39.7% from FB, and 53.0 and 45.5% from MP, respectively. The standardized apparent maximum efflux to HDL was 76% from rat SMC, 45 and 31% from monkey and rabbit SMC, 139% from FB and 166% from MP. Accordingly, the reaction with free apolipoproteins caused significant net reduction of cellular cholesterol, predominantly in cholesteryl ester, in FB and MP, but not in SMC. While the efflux Km with apoA-I and A-II were 7.5 and 4.5 micrograms/ml for MP, those for SMC and FB were both 1 microgram/ml or lower, as low as 1/1500 and 1/500 of their plasma concentrations, respectively. The apparent efflux Km for HDL were, on the other hand, all in the range of 36 to 65 micrograms of protein/ml for SMC, FB, and MP, showing that the mode of cholesterol exchange of these cells with lipoprotein surface is not significantly different from each other. Thus, peripheral cells such as FB may provide a significant source of HDL by interacting with extracellular free apolipoproteins in interstitial fluid, reducing intracellularly accumulated cholesterol. However, SMC seem very resistant to this interaction, suggesting that atheromatous lesions predominantly consisting of SMC are resistant to regression. |