Transbilayer distribution of cholesterol is modified in brain synaptic plasma membranes of knockout mice deficient in the low-density lipoprotein receptor, apolipoprotein E, or both proteins.

Igbavboa U, Avdulov NA, Chochina SV, Wood WG.

Geriatric Research, Education and Clinical Center, VA Medical Center, and Department of Pharmacology, University of Minnesota School of Medicine, Minneapolis 55417, U.S.A.

Both apolipoprotein E (apoE) and the low-density lipoprotein (LDL) receptor are present in brain; however, little is known regarding the function of these proteins in brain, in particular with respect to brain cholesterol. The role of apoE and the LDL receptor in modulating the transbilayer or asymmetric distribution of cholesterol in the exofacial and cytofacial leaflets of synaptic plasma membranes (SPMs) was examined in mutant mice deficient in apoE, the LDL receptor, or both proteins by using the fluorescent sterol dehydroergosterol and fluorescent quenching procedures. Fluidity of the exofacial and cytofacial leaflets was also measured. Cholesterol asymmetry of SPMs was altered in the mutant mice, with the largest effect observed in the LDL receptor-deficient mice. There was an approximately twofold increase in the percent distribution of cholesterol in the exofacial leaflet of the LDL receptor-deficient mice (32%) compared with C57BL/6J mice (15%). Mice deficient in apoE or both proteins also showed a significantly higher percent distribution of cholesterol (23 and 26%, respectively) in the exofacial leaflet compared with the C57BL/6J mice. Although the percent distribution of cholesterol was highest in the exofacial leaflet of the LDL receptor-deficient mice, fluidity of the exofacial leaflet of that group was significantly lower. However, the cholesterol-to-phospholipid ratio of SPMs of the LDL receptor-deficient mice was significantly lower, and this difference was largely the result of a significant increase in the total amount of SPM phospholipid. This study demonstrates for the first time that SPM lipid structure is altered in mice deficient in apoE or the LDL receptor. Although the mechanism that maintains the asymmetric distribution of cholesterol in plasma membranes is not well understood, data of the present experiments indicate that both apoE and the LDL receptor are involved in maintaining the transbilayer distribution of cholesterol.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9326295&dopt=Abstract cholesterol




Effect of response to a low-fat diet among adolescent males on their adult blood cholesterol levels.

Ellison RC, Moore LL, Proctor MH, Nguyen US, Schaefer EJ, Stare FJ.

Evans Department of Medicine, Boston University School of Medicine, Massachusetts 02118, USA.

BACKGROUND: While primary prevention of adult cardiovascular diseases should begin early, there are problems in identifying children at increased risk of future disease. METHODS: We did a follow-up study in 1991-1992 of 100 male former students at a boarding high school who had blood cholesterol measured in 1970-1971 both prior to and following a school-wide, reduced-fat dietary intervention. We compared adult cholesterol levels of the 50 subjects whose cholesterol decreased > or = 16.5% (the median decrease) following the 1970-1971 intervention (Diet-Sensitive) with the 50 whose response was < 16.5% (Non-Diet-Sensitive). RESULTS: Blood cholesterol of adults who were Diet-Sensitive in 1970-1971 was 4.2 mg/dl lower than their baseline values in adolescence, while adults classified as Non-Diet-Sensitive as adolescents showed a 15.9 mg/ dl increase in cholesterol over 21 years. Adjusting for baseline adolescent values, Non-Diet-Sensitive subjects were 4.8 (95% CI 1.4, 15.9) times as likely as Diet-Sensitive subjects to have adult cholesterol > or = 200 mg/ dl. Also, Diet-Sensitive adults on a low-fat diet had adult blood cholesterol levels > 20 mg/dl lower than Non-Diet-Sensitive adults on a similar diet (180.1 vs 202.1 mg/dl, respectively). CONCLUSIONS: Degree of response to a low-fat, low-cholesterol diet during adolescence may identify male subjects who will have differing patterns of cholesterol change over time.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9327478&dopt=Abstract cholesterol




A cholesterol-rich diet causes a greater hypercholesterolemic response in pregnant than in nonpregnant rats and does not modify fetal lipoprotein profile.

Munilla MA, Herrera E.

Faculty of Experimental Sciences, University of San Pablo-CEU, E-28668 Madrid, Spain.

To determine whether pregnancy modifies the hyperlipidemic response to a cholesterol-rich diet, pregnant and virgin rats were fed a semisynthetic diet supplemented (CRD) or not (CD) with 2% cholesterol and 1% cholic acid and studied at d 20 of treatment and/or gestation. Plasma triglycerides, free fatty acids and glycerol and liver triglycerides were greater in pregnant than in virgin rats fed CRD. The increase in both plasma and liver cholesterol caused by CRD did not differ in the two groups. In rats fed CD, hepatic lipase activity in liver was lower in pregnant than in virgin rats, while in those fed CRD, virgin rats had lower activity than those fed CD. Plasma VLDL-triglycerides were higher and LDL-triglycerides lower in pregnant than in virgin rats fed CD. Among those fed CRD, pregnant rats had a higher triglyceride concentration in VLDL and HDL than virgin rats. Cholesterol concentration was higher in VLDL and IDL and lower in HDL in both groups fed CRD than in those fed CD, while cholesterol level in LDL was higher only in pregnant rats fed CRD than in those fed CD. Whereas placental cholesterol concentration was higher in pregnant rats fed CRD than CD, maternal CRD intake did not modify fetal plasma lipoprotein concentrations, fetal body weight or litter size, indicating a lack of cholesterol transfer by the rat placenta. Results therefore show a greater responsiveness to CRD in pregnant than in virgin rats, and we propose that CRD promotes greater liver VLDL-production and lower LDL removal in pregnant than in virgin rats.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9349853&dopt=Abstract cholesterol




The effect of cigarette smoking during pregnancy on cord blood lipid, lipoprotein and apolipoprotein levels.

Iscan A, Yigitoglu MR, Ece A, Ari Z, Akyildiz M.

Department of Pediatrics, Faculty of Medicine, University of Celal Bayar, Manisa, Turkey.

We examined the relationship between maternal smoking during pregnancy and serum lipid, lipoprotein and apolipoprotein levels in newborns. Serum concentrations of total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, apolipoprotein A-1, apolipoprotein B and lipoprotein (a) were assessed in blood samples from 38 mothers who were smokers and their newborns obtained at delivery and compared to blood sample from 42 nonsmokers and their newborns. As compared with newborns of nonsmoker mothers, newborns of smoker mothers showed a lower mean level of high density lipoprotein cholesterol (21 versus 26 mg/dl, p < 0.01), a higher total cholesterol to high density lipoprotein cholesterol (4.7 versus 3.7, p < 0.01), a higher low density lipoprotein cholesterol to high density lipoprotein cholesterol ratios (3.2 versus 2.3, p < 0.05), a lower mean level of apolipoprotein A-1 (105 versus 129 mg/dl, p < 0.01) and a higher apolipoprotein B to apolipoprotein A-1 ratio (0.44 versus 0.3, p < 0.01). These parameters were also different between smoker and nonsmoker mothers. There were no significant differences in TC, TG, LDL-C, Apo B and Lp (a) values between the two newborn groups. These data suggest that maternal smoking during pregnancy markedly affects lipid metabolism in the fetus.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9350146&dopt=Abstract cholesterol




Total serum cholesterol in relation to psychological correlates in parasuicide.

Garland M, Hickey D, Corvin A, Golden J, Fitzpatrick P, Cunningham S, Walsh N.

Department of Psychiatry, St Vincent's University Hospital, Dublin, Ireland. mgarland svherc.ucd.ie

BACKGROUND: Low cholesterol may act as a peripheral marker for parasuicide. AIMS: To examine the relationship between total serum cholesterol and psychological parameters in parasuicide. METHOD: Total serum cholesterol and self-rated scores for impulsivity, depression and suicidal intent were measured in 100 consecutive patients following parasuicide, pair-matched with normal and psychiatric control groups. RESULTS: Backward, stepwise multiple regression analysis revealed a significantly lower mean cholesterol in the parasuicide population (P < 0.01). Across all groups there was an independent significant (P < 0.01) negative correlation between cholesterol and self-reported scores of impulsivity. No correlation existed between cholesterol and scores for depression or suicidal intent. CONCLUSIONS: The data confirm previous reports of low cholesterol in parasuicide. This is the first reported investigation of the construct of impulsivity in relation to cholesterol. We hypothesise that the reported increased mortality in populations with low cholesterol may derive from increased suicide and accident rates consequent on increased tendencies to impulsivity in these populations.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10945093&dopt=Abstract cholesterol




U.K. Prospective Diabetes Study 27. Plasma lipids and lipoproteins at diagnosis of NIDDM by age and sex.

[No authors listed]

OBJECTIVE: To compare fasting plasma lipids and lipoproteins in male and female patients at diagnosis of NIDDM and to examine age and sex differences in lipid concentrations. RESEARCH DESIGN AND METHODS: Cross-sectional study of fasting plasma total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride in 2,139 male and 1,574 female white patients, aged 25-65 years, at diagnosis of NIDDM. RESULTS: At diagnosis of NIDDM, the mean age +/- SD for men was 52 +/- 9 and 53 +/- 9 years for women; BMI was 28.3 +/- 4.9 and 30.8 +/- 6.7 kg/m2, and fasting plasma glucose was 11.6 +/- 3.6 and 12.4 +/- 3.8 mmol/l, respectively. The mean total and LDL cholesterol were higher in female than in male NIDDM patients, 5.8 +/- 1.2 vs. 5.5 +/- 1.1 and 3.9 +/- 1.1 vs. 3.6 +/- 1.0 mmol/l (both P < 0.001), respectively, while triglyceride levels were similar: geometric mean (1 SD interval) for men and women was 1.8 (1.1-3.1) vs. 1.8 (1.1-2.9) mmol/l. HDL cholesterol was higher in female than in male NIDDM patients, 1.09 +/- 0.2 vs. 1.01 +/- 0.24 mmol/l (P < 0.001); the sex differential for HDL cholesterol was 7% in NIDDM patients compared with 22% in the general population. Data analysis by 5-year age bands showed a significant trend toward lower total cholesterol and triglyceride and higher HDL cholesterol in men diagnosed above the age of 50 years. In female NIDDM patients, lipid concentrations increased with age of diagnosis but reached a plateau above the age of 50 years. CONCLUSIONS: The effect of NIDDM, observed at diagnosis, on plasma lipid and lipoprotein levels is more pronounced in women than in men. This may explain in part why the cardiovascular risk is proportionally higher in female patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9353608&dopt=Abstract cholesterol




Comparative hypocholesterolemic effects of six dietary oils in cholesterol-fed rats after long-term feeding.

Fukushima M, Matsuda T, Yamagishi K, Nakano M.

Department of Bioresource Chemistry, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido, Japan.

Rats (8 wk of age) fed a conventional diet were shifted to diets containing 10% Oenothera biennis Linn oil (OBLO, linoleic acid + gamma-linolenic acid) from a wild plant, evening primrose oil (EPO, linoleic acid + gamma-linolenic acid) from a cultivated plant, bio-gamma-linolenic acid oil from mold (BIO, palmitic acid + oleic acid + linoleic acid + gamma-linolenic acid), safflower oil (linoleic acid), palm oil (PLO, palmitic acid + oleic acid + linoleic acid), or soybean oil (linoleic acid + alpha-linolenic acid) with 0.5% cholesterol for 13 wk. Though there were no significant differences in the food intake among the groups, the body weight gain of the OBLO group was significantly lower than that of the other groups except for the BIO and PLO groups, and that of the EPO and SBO groups were the highest among the groups. The liver weight of the OBLO group was significantly lower than that of other groups, and that of the PLO group was the highest among the groups. The serum total cholesterol and very low density lipoprotein (VLDL) + intermediate density lipoprotein (IDL) + low density lipoprotein (LDL) cholesterol concentrations of the OBLO and EPO groups were consistently lower than those in the other groups. However, those of the BIO group were higher than those in the OBLO and EPO groups. The liver cholesterol concentration of the PLO group was the highest among all groups except for the EPO group. The fecal neutral sterol and bile acid extraction of the BIO group tended to increase compared to the other groups. The results of this study demonstrate that OBLO and EPO inhibit the increasing of serum total cholesterol and VLDL + IDL + LDL-cholesterol concentrations in the presence of excess cholesterol in the diet compared with the other dietary oils.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9358433&dopt=Abstract cholesterol




Soy protein concentrate and isolated soy protein similarly lower blood serum cholesterol but differently affect thyroid hormones in hamsters.

Potter SM, Pertile J, Berber-Jimenez MD.

Department of Food Science and Human Nutrition, University of Illinois at Urbana/Champaign, IL 61801, USA.

There is a wide variation in the hypocholesterolemic response to ingestion of soy protein in humans. One possible explanation is that the different soy protein preparations used contain different spectra of biologically active components. This could affect a number of indices including thyroid hormone status. An increased level of thyroxine has been proposed as an underlying mechanism of the hypocholesterolemic effect of soy protein. The objective of this study was to determine if serum cholesterol and thyroid hormone concentrations differed because of feeding soy protein from different sources. Twenty-nine male weanling golden Syrian hamsters were fed rations containing 25 g/100 g protein from either isolated soy protein (ISP), soy protein concentrate (SPC) or casein for 35 d. Serum total cholesterol concentrations were lower in hamsters fed ISP and SPC compared with those fed casein (P < 0.05). No differences in cholesterol concentrations were observed in lipoprotein fractions. Serum thyroxine and free thyroxine were greater only in hamsters fed ISP than in those fed casein (P < 0.05), whereas triiodothyronine concentrations were higher in casein-fed than in SPC-fed hamsters (P < 0.05). Results indicate that protein from ISP and SPC are both effective in lowering blood cholesterol concentrations, whereas only ISP increases thyroxine concentrations. Therefore, it appears unlikely that modulation of thyroid hormone status is responsible for the cholesterol-lowering effect of soy protein.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8759373&dopt=Abstract cholesterol




Thrombophilia in patients with hypercholesterolemia.

Chan P, Tomlinsoin B, Tsai CW, Pan WH, Lee YS.

Department of Medicine, Taipei Municipal Chung-Hsiao Hospital, Taiwan.

To investigate a possible interrelationship between hypercholesterolemia and the coagulation and fibrinolytic system, the Cardiovascular Disease Risk Factor Two-Township Study in Taiwan was undertaken as a longitudinal prospective study focusing on the evolution of cardiovascular disease risk factors, with an emphasis on hemostatic factors. Hemostatic parameters measured in this study included prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, factor VIIc, factor VIIIc, antithrombin III, and plasminogen. Subjects of both sexes with hypercholesterolemia (> 6.2 mmol/L) also had significant elevations of diastolic blood pressure, plasma glucose, triglycerides, fibrinogen, and factor VIIc and reduced PT and APTT compared with subjects with lower cholesterol. The hypercholesterolemic women additionally had significant elevations of systolic blood pressure and factor VIIc. Levels of the anticoagulant factors, antithrombin III and plasminogen, were also higher in both hypercholesterolemic men and women. In men, only factor VIIIc had no statistically significant elevation. In women, only PT showed no statistical difference. Established coronary risk factors such as fibrinogen and factor VIIc showed remarkable elevations in patients of both sexes. Using Pearson correlation and multiple regression, the most significant parameter related to cholesterol level was factor VIIc. The present results show that hemostatic abnormalities do exist in patients with hypercholesterolemia, and this thrombophilic phenomenon sheds further light on the study of higher cardiovascular mortality in these subjects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8769353&dopt=Abstract cholesterol