Dietary palmitic acid (16:0) enhances high density lipoprotein cholesterol and low density lipoprotein receptor mRNA abundance in hamsters.

Lindsey S, Benattar J, Pronczuk A, Hayes KC.

Foster Biomedical Research Laboratory, Brandeis University, Waltham, Massachusetts 02254.

In order to examine the qualitative effect of different fats and specific fatty acids on plasma lipids and lipoprotein metabolism, six low fat, cholesterol-free diets were fed to young male hamsters (10/group) for a 4-week period. Fat blends were formulated with coconut oil, palm oil, soybean oil, high oleic acid safflower oil, butter, corn oil, and canola oil. Diets contained 13% energy as fat and dietary polyunsaturate/saturate ratios ranged from 0.12 to 1.04, one of which incorporated the American Heart Association-recommended concentrations of saturates, monoenes, and polyenes and another reflected the current American Fat Blend. In three diets the polyunsaturate/monounsaturate/saturate ratio was held constant while only the 12:0, 14:0, and 16:0 were varied. Plasma lipoproteins and apoproteins were assessed in conjunction with the abundance of specific hepatic and intestinal mRNA for the low density lipoproteins (LDL) receptor and various apolipoproteins associated with cholesterol metabolism. The plasma cholesterol response was lowest with the American Heart Association blend and equally elevated by the more saturated, low polyene diets (polyunsaturate/saturate, 0.12-0.38). Replacing 12:0 plus 14:0 from coconut oil with 16:0 as palm oil induced a significant increase in high density lipoprotein (HDL) cholesterol with a trend toward decreased LDL. These shifts in lipoprotein cholesterol were corroborated by measures of the LDL/HDL ratio, the plasma apolipoprotein B/apolipoprotein A1 ratio, and differences in the synthesis of apolipoproteins and the LDL receptor based on estimates of the mRNA for these proteins in the liver and gut, using specific cDNA probes for apolipoprotein A1, apolipoprotein B, apolipoprotein E, and the LDL receptor. Although it has been suggested that dietary polyenes lower total plasma cholesterol, including HDL, and that saturated fat increases both these pools of cholesterol, the current data represents the first evidence that a specific saturated fatty acid, i.e., palmitic acid, may enhance HDL production.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2236108&dopt=Abstract cholesterol




Erythrocyte fatty acids, plasma lipids, and cardiovascular disease in rural China.

Fan WX, Parker R, Parpia B, Qu YS, Cassano P, Crawford M, Leyton J, Tian J, Li JY, Chen JS, et al.

Institute of Nutrition and Food Hygiene, Chinese Academy of Preventive Medicine, Beijing.

Cardiovascular disease (CVD) mortality (coronary heart disease, hypertensive heart disease, and stroke), plasma lipids, and red blood cell fatty acid composition were examined in an ecologic study in 65 rural counties in the People's Republic of China. Means of plasma total cholesterol, triglyceride, low-density-lipoprotein (LDL) cholesterol, and high-density-lipoprotein (HDL) cholesterol concentrations were substantially lower and the ratio of HDL cholesterol to total cholesterol was higher in this Chinese population than in Western populations. Mortality rates for CVD in China were well below Western values. Within China neither plasma total cholesterol nor LDL cholesterol was associated with CVD. A strong inverse correlation between red blood cell oleate concentrations and CVD was observed. However, red blood cell oleate concentrations were not associated with plasma cholesterol but were strongly negatively associated with arachidonate concentrations, suggesting potential diminution of CVD by oleate through reduced platelet aggregability. The results indicate that geographical differences in CVD mortality within China are caused primarily by factors other than dietary or plasma cholesterol.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2239777&dopt=Abstract cholesterol




[The effects of the cholesterol synthesis inhibitor simvastatin in patients with hypercholesterolemia with and without diabetes mellitus]

[Article in Dutch]

van Deursen RT, Nieuwenhuijzen Kruseman AC, Degenaar CP, Wolffenbuttel BH.

Afd. Inwendige Geneeskunde, Academisch Ziekenhuis, Maastricht.

We studied the short-term effects of simvastatin on lipid variables in 33 dyslipidemic patients without and 18 with diabetes mellitus who were on a lipid-lowering diet for at least 3 months. Six diabetic patients had type I, and 12 had type II diabetes mellitus, of whom 5 were using insulin. In the whole group total cholesterol decreased by 28%, from 9.35 (SD 2.10) mmol/l to 6.69 (SD 1.47) mmol/l after 3 months and 6.60 (SD 1.27) mmol/l after 6 months (mean daily dose of simvastatin 21 (SD 12) mg). Calculated LDL-cholesterol showed a decrease of 38%, HDL-cholesterol increased by 10% and plasma triglycerides decreased by 13%. In patients receiving 10, 20, or 40 mg simvastatin daily, the following changes were observed: total cholesterol -26, -31 and -34% and LDL-cholesterol -37, -38 and -39%, respectively. The effect of simvastatin in the diabetic patients was comparable with that in the non-diabetic individuals, although in the diabetics LDL-cholesterol before therapy was lower, as was the daily dose of simvastatin after 6 months (14 versus 24 mg). In the diabetic patients blood glucose control, measured as HbA1c, was not affected. One patient discontinued therapy because of stomach complaints. Our results show that a low daily dose (10 mg) of simvastatin effectively lowers plasma total and LDL-cholesterol and that the drug can be safely used in diabetic patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2247172&dopt=Abstract cholesterol




Influences of refined konjac meal on the levels of tissue lipids and the absorption of four minerals in rats.

Hou YH, Zhang LS, Zhou HM, Wang RS, Zhang YZ.

School of Public Health, West China University of Medical Sciences, Chengdu.

This paper reports a study on the hypocholesterolemic effect of the refined konjac meal (RKM) containing about 80% glucomannan prepared from the tubers of Amorphophallus konjac K. Koch. Male and female Sprague-Dawley rats, 5 weeks old, were divided into five groups and fed a normal basal diet, a hypercholesterolemic diet (control diet), and three test diets (RKM added to the control diet at levels of 2.5, 5, and 10%, respectively) for 12 weeks. The results obtained indicate that RKM could markedly lower the cholesterol levels in the serum and the liver of rats eating hypercholesterolemic diets. At the end of the 4th week of feeding experiment, the serum cholesterol levels in the 5 and the 10% RKM groups and the liver cholesterol level in the 10% RKM group were significantly lower than those in the control groups. At the end of the 12th week, the serum cholesterol levels of all the three RKM groups were lowered to a normal level as was the liver cholesterol level of the 10% RKM group. The lipotropic effect of RKM was also confirmed by histopathologic examination of the livers. In addition to the hypocholesterolemic effects, RKM diets also increased stool bulk. Minor effects on the absorption and utilization of Ca, Fe, Zn, and Cu were found.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2252550&dopt=Abstract cholesterol




The prevalence of hyperlipidemia in renal transplant recipients. Associations with immunosuppressive and antihypertensive therapy.

Bittar AE, Ratcliffe PJ, Richardson AJ, Raine AE, Jones L, Yudkin PL, Carter R, Mann JI, Morris PJ.

Nuffield Department of Surgery, Churchill Hospital, Oxford, United Kingdom.

To determine the extent of persisting hyperlipidemia in renal transplant recipients receiving modern maintenance immunosuppressive and antihypertensive therapy we compared plasma levels of total and high-density lipoprotein and triglyceride in 275 renal transplant recipients with stable graft function with age- and sex-matched groups from the local general population (n = 4055). Total cholesterol and triglyceride were higher in transplanted patients in all age groups, but the difference was much more striking in women. Plasma levels of HDL cholesterol were similar or slightly lower in transplanted patients. Association with parameters of graft function, immunosuppressive therapy, and antihypertensive therapy were studied within the transplanted population using multiple regression. Total cholesterol was significantly and independently associated with age, sex, diuretic therapy, and urinary protein. In 127/134 (95%) of patients the diuretic was a loop diuretic. None of the other classes of antihypertensive drug was independently associated with serum cholesterol. The only variables significantly associated with HDL cholesterol were sex and the plasma creatinine. Plasma triglyceride was significantly and independently associated with both diuretic therapy and beta-blocker therapy and with age, urinary protein excretion, and plasma albumin. Plasma cholesterol, HDL cholesterol, and triglyceride levels were almost identical in patients receiving triple therapy (cyclosporine 3-5 mg/kg; prednisolone 7-10 mg o.d.; azathioprine 1-1.5 mg/kg) to those in patients receiving conventional immunosuppression (prednisolone 7-10 mg o.d.; azathioprine 2-2.5 mg/kg). Thus these results do not support the existence of a persisting long-term effect of cyclosporine on plasma cholesterol and triglyceride at these doses of the drug. The more striking abnormality of plasma cholesterol and triglyceride in females is unexplained but might be connected with greater sensitivity to low doses of corticosteroids.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2256173&dopt=Abstract cholesterol




Cholesterol is required for the reconstruction of the sodium- and chloride-coupled, gamma-aminobutyric acid transporter from rat brain.

Shouffani A, Kanner BI.

Department of Biochemistry, Hadassah Medical School, Hebrew University, Jerusalem, Israel.

The reconstruction of the purified sodium- and chloride-coupled gamma-aminobutyric acid transporter from rat brain into asolectin liposomes requires the addition of brain lipids (Radian, R., and Kanner, B. I. (1985) J. Biol. Chem. 260, 11859-11865). The reconstitution assay was used to identify the component(s) from brain lipids responsible for the stimulation during the fractionation of brain lipids. The distribution of the active component was found to be similar to that of cholesterol. Furthermore, cholesterol was found to mimic the effect of brain lipids and it stimulated the transport activity up to 20-fold. Optimal reconstituted transport activity was achieved with mixtures of cholesterol and any one of several phospholipids, such as phosphatidylcholine, phosphatidylserine or phosphatidylglycerol. gamma-Aminobutyric acid transport in these liposomes of defined composition exhibited all the properties of the native transporter, such as the absolute dependence on sodium and chloride and electrogenicity. Cholesterol could not be replaced by cholest-4-en-3one and other steroids, and thus its effect is probably not due to effects on membrane fluidity. The requirement was also not due to effects on intactness of the liposomes or incorporation of proteins into them. Furthermore it was found that the reconstitution of the sodium and potassium coupled L-glutamic acid transporter from rat brain also required cholesterol. However, in this case the optimal activity was reached by 4-5-fold lower levels of cholesterol than those necessary for gamma-aminobutyric acid transport. When cholesterol depletion from the transporters was incomplete, addition of exogenous brain lipids was not required. Thus, if the cholesterol was still associated with the transporter proteins, its final concentration, as a fraction of the total lipids present in the reconstitution mixture, was only about 0.01 mol%. Thus, it is likely that the effects of cholesterol are due to direct interactions with the cotransporters and not to an average effect on membrane properties.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2318845&dopt=Abstract cholesterol




Ten-year mortality from cardiovascular disease in relation to cholesterol level among men with and without preexisting cardiovascular disease.

Pekkanen J, Linn S, Heiss G, Suchindran CM, Leon A, Rifkind BM, Tyroler HA.

Department of Biostatistics, University of North Carolina, Chapel Hill.

To determine the associations of total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol with mortality from coronary heart disease and cardiovascular disease, we studied 2541 white men who were 40 to 69 years old at base line and followed them for an average of 10.1 years. Seventeen percent had some manifestation of cardiovascular disease at base line, whereas the others did not. Among the men who had cardiovascular disease at base line, we found, after multivariate adjustment, that those with "high" blood cholesterol levels (above 6.19 mmol per liter) had a risk of death from cardiovascular disease, including coronary heart disease, that was 3.45 times higher (95 percent confidence interval, 1.63 to 7.33) than that for men with "desirable" blood cholesterol levels (below 5.16 mmol per liter). The corresponding hazard ratios were 5.92 (95 percent confidence interval, 2.59 to 13.51) for LDL cholesterol levels above 4.13 mmol per liter as compared with those below 3.35 mmol per liter, and 6.02 (95 percent confidence interval, 2.73 to 13.28) for HDL cholesterol levels below 0.90 mmol per liter as compared with those above 1.16 mmol per liter. All three lipid levels were also significant predictors of death from coronary heart disease alone (P less than 0.005). Total cholesterol and LDL cholesterol levels were also significant predictors of death from cardiovascular and coronary heart disease in men without preexisting cardiovascular disease, although at a lower level of absolute risk of death. Thus, the 10-year risk of death from cardiovascular disease for a man with preexisting cardiovascular disease increased from 3.8 percent to almost 19.6 percent with increasing levels of total cholesterol from "desirable" to "high," whereas the corresponding risk for a man who was free of cardiovascular disease at base line increased from 1.7 percent to 4.9 percent. Our findings suggest that total, LDL, and HDL cholesterol levels predict subsequent mortality in men 40 to 69 years of age, especially those with preexisting cardiovascular disease.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2342536&dopt=Abstract cholesterol




Phenotypic effects of apolipoprotein structural variation on lipid profiles. III. Contribution of apolipoprotein E phenotype to prediction of total cholesterol, apolipoprotein B, and low density lipoprotein cholesterol in the healthy women study.

Eichner JE, Kuller LH, Ferrell RE, Meilahn EN, Kamboh MI.

Department of Epidemiology, School of Public Health, University of Pittsburgh, Pennsylvania 15261.

The apolipoprotein (apo) E structural locus has been shown to influence concentrations of total cholesterol, apo B, and low density lipoprotein (LDL) cholesterol in population studies. Apo E has six phenotypes resulting from three common alleles at this locus. In the present study, we have typed 473 healthy white women for apo E. At baseline in 1984, all women were premenopausal. To date, 109 of these women have become postmenopausal and are not on hormone therapy. Statistical analyses were done on both pre- and postmenopausal groups to assess the influence of menopausal status in combination with the apo E locus on lipid profile. Nine lipoprotein lipids and apolipoproteins were categorized by three apo E phenotypes: apo E3-2, apo E3-3, and apo E4-3. These were compared in analysis of variance. At baseline, the apo E3-2 phenotype showed the lowest average concentrations of total cholesterol (170 mg/dl), apo B (80 mg/dl), and LDL cholesterol (91 mg/dl), while the apo E4-3 phenotype demonstrated the highest average concentrations of total cholesterol (192 mg/dl), apo B (104 mg/dl), and LDL cholesterol (116 mg/dl) (p less than or equal to 0.0004). Apo E3-3 homozygotes were intermediate on all three quantitative variables. The postmenopausal subset showed the same trends by phenotype, with overall increases in total cholesterol, apo B, LDL cholesterol, and triglycerides, regardless of phenotype. Women who remained premenopausal generally showed smaller increases in these same measures. Our results suggest that, on average, the lower lipoprotein values for the apo E3-2 phenotype are maintained through early menopause despite a worsening of lipid profiles for all women as they age.(ABSTRACT TRUNCATED AT 250 WORDS)

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2344296&dopt=Abstract cholesterol




Comparison of breast-feeding and formula feeding on intestinal and hepatic cholesterol metabolism in neonatal pigs.

Jones PJ, Hrboticky N, Hahn P, Innis SM.

Division of Human Nutrition, University of British Columbia, Vancouver, Canada.

Infant formulas (IFs) contain reduced cholesterol concentrations compared with breast milk (SM); how neonatal cholesterol metabolism responds to this difference is largely unknown. The effect of exclusive feeding of SM vs low-cholesterol IF on intestinal and hepatic cholesterol concentrations and synthesis during early postnatal development were compared in piglets. Animals were killed at birth or on days 5, 10, 15, or 25 postpartum. Plasma cholesterol concentrations were higher in SM-fed than in IF-fed piglets on days 15 and 25. In intestine both HMG-CoA reductase activity and 3H2O incorporation rates into cholesterol were similar for both groups or reduced in the IF-fed group at days 15 and 25. In liver, HMG-CoA reductase activity was higher in IF-fed than in SM-fed piglets on days 5, 10, and 15. Results indicate that during the early postpartum period, response to lower cholesterol intakes with IF occurs by increasing hepatic sterol synthesis whereas intestinal synthesis is largely unaffected.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2349934&dopt=Abstract cholesterol