| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Degradation of phospholipid transfer protein (PLTP) and PLTP-generated pre-beta-high density lipoprotein by mast cell chymase impairs high affinity efflux of cholesterol from macrophage foam cells Lee, M., J. Metso, et al. (2003), J Biol Chem 278(15): 13539-45. Abstract: Human atherosclerotic lesions contain mast cells filled with the neutral protease chymase. Here we studied the effect of human chymase on (i) phospholipid transfer protein (PLTP)-mediated phospholipid (PL) transfer activity, and (ii) the ability of PLTP to generate pre-beta-high density lipoprotein (HDL). Immunoblot analysis of PLTP after incubation with chymase for 6 h revealed, in addition to the original 80-kDa band, four specific proteolytic fragments of PLTP with approximate molecular masses of 70, 52, 48, and 31 kDa. This specific pattern of PLTP degradation remained stable for at least 24 h of incubation with chymase. Such proteolyzed PLTP had reduced ability (i) to transfer PL from liposome donor particles to acceptor HDL(3) particles, and (ii) to facilitate the formation of pre-beta-HDL. However, when PLTP was incubated with chymase in the presence of HDL(3), only one major cleavage product of PLTP (48 kDa) was generated, and PL transfer activity was almost fully preserved. Moreover, chymase effectively depleted the pre-beta-HDL particles generated from HDL(3) by PLTP and significantly inhibited the high affinity component of cholesterol efflux from macrophage foam cells. These results suggest that the mast cells in human atherosclerotic lesions, by secreting chymase, may prevent PLTP-dependent formation of pre-beta-HDL particles from HDL(3) and so impair the anti-atherogenic function of PLTP. |
| Degradation of plasma membrane phosphatidylcholine appears not to affect the cellular cholesterol distribution Porn, M. I., M. P. Ares, et al. (1993), J Lipid Res 34(8): 1385-92. Abstract: To clarify the role of possible cholesterol/phosphatidylcholine interactions in cellular cholesterol distribution, we have used a phosphatidylcholine-specific phospholipase C from Bacillus cereus to degrade the cell surface phosphatidylcholine of cultured human fibroblasts. Of cellular phosphatidylcholine, approximately 15% was susceptible to degradation by the phospholipase. In spite of the dramatic redistribution of cellular cholesterol that can be observed after sphingomyelin depletion, the degradation of cell surface phosphatidylcholine did not affect the distribution of cholesterol in fibroblasts. In cholesterol-depleted cells as well as in cholesterol-loaded cells, the size of the cell surface cholesterol pool (susceptible to cholesterol oxidase) remained unchanged after phosphatidylcholine degradation. The rate of cholesterol esterification with 3Holeic acid and the rate of 3Hcholesterol efflux from fibroblasts to high density lipoproteins also remained unchanged after degradation of plasma membrane phosphatidylcholine. An increase in the level of 3Hcholesterol efflux to high density lipoproteins was observed after degradation of plasma membrane sphingomyelin with exogenous sphingomyelinase, in-contrast to earlier reports, where no such effect was observed. The results suggest that interactions between cholesterol and phosphatidylcholine in the fibroblast plasma membranes are less important than cholesterol/sphingomyelin interactions for the asymmetric distribution of cellular cholesterol. |
| Degranulation and superoxide production depend on cholesterol in PLB-985 cells Kaldi, K., A. Kalocsai, et al. (2003), Biochem Biophys Res Commun 310(4): 1241-6. Abstract: The effect of agents disrupting cholesterol-rich microdomains of the cell membrane was studied on the chemoattractant receptor (FPR and FRPL1) coupled effector responses of promyelocytic PLB-985 cells. Both methyl-beta-cyclodextrin (MbetaCD) and filipin III inhibited exocytosis of primary granules and O(2)(-) production induced by stimulation of either chemotactic receptor. Alteration of calcium homeostasis of MbetaCD-treated cells does not account for the impairment of the effector responses. Disruption of microfilaments by cytochalasin B (CB) partially reverses the inhibitory effect of cholesterol depletion. Our results provide functional support for the involvement of cholesterol-rich membrane domains in the signaling of chemotactic receptors and call the attention to the possible role of microfilaments in the organization of lipid microdomains. |
| Degree of fatty acyl chain unsaturation in biliary lecithin dictates cholesterol nucleation and crystal growth Tazuma, S., H. Ochi, et al. (1994), Biochim Biophys Acta 1215(1-2): 74-8. Abstract: To clarify factors involved in the formation of cholesterol gallstones, we studied the relationship between the degree of fatty acyl chain unsaturation of biliary lecithin and bile metastability. We used supersaturated model bile solutions (molar taurocholate/lecithin/cholesterol ratio (73:19.5:7.5), total lipid concentration 9 g/dl) that contained equimolar egg yolk or soybean lecithins or a sn-1 palmitoyl, sn-2 linoleoyl phosphatidylcholine. Gel permeation chromatographic studies showed that the vesicular cholesterol distribution and dimension were inversely related to the degree of unsaturation of the lecithin species, estimated by reverse phase, high-performance liquid chromatography. Differential interference contrast microscopy and assay of cholesterol crystal growth showed that a higher degree of fatty acyl chain unsaturation of the lecithin species was associated with a faster nucleation time and rate of crystal growth. Our results suggest that vesicular lecithins containing more unsaturated fatty acyl chains bind less tightly to cholesterol than lecithins containing predominantly saturated fatty acids, and that the biliary lecithin species dictates, in part, the nucleation and growth of cholesterol crystals in bile. |
| Degree of the reliability of single measurement of cholesterol contents (literature review) Tvorogova, M. G., A. A. Saatov, et al. (1997), Klin Lab Diagn(1): 4-6. |
| Dehydroepiandrosterone sulfate, cholesterol, hemoglobin, and anthropometric measures related to growth in male adolescents Arquitt, A. B., B. J. Stoecker, et al. (1991), J Am Diet Assoc 91(5): 575-9. Abstract: Sixty-four white boys between 10.6 and 14.3 years old participated in an adolescent nutrition assessment study evaluating dehydroepiandrosterone sulfate (DHEAS) as a measure of maturation. DHEAS, an adrenal androgen, is low in childhood and rises with the development of secondary sexual characteristics. Biochemical measures included plasma DHEAS assessed by radioimmunoassay, cholesterol assessed by an enzymatic method, and hemoglobin assessed by the cyanmethemoglobin method. Midarm muscle area (MAMA) was calculated from midarm circumference and triceps fatfold measurements. DHEAS was correlated significantly with height, weight, MAMA, and hemoglobin. By age, significant differences were found for height, weight, and MAMA, but not for any of the biochemical measures. For boys with DHEAS concentration less than 3 mumol/L, values for height, weight, body mass index, MAMA, and hemoglobin were significantly different from those for boys with higher DHEAS concentrations. No significant differences were found for age or nutrient intakes by DHEAS concentration groups. Mean plasma cholesterol concentrations decreased with increases in age and with maturation evidenced by higher DHEAS concentration. Cholesterol concentration was negatively correlated with height and MAMA. Mean nutrient intakes estimated by a quantitative food frequency questionnaire met or exceeded the Recommended Dietary Allowances for these age groups. DHEAS identified maturation differences in male adolescents. |
| Delapril slows the progression of atherosclerosis and maintains endothelial function in cholesterol-fed rabbits Hernandez, A., L. Barberi, et al. (1998), Atherosclerosis 137(1): 71-6. Abstract: The renin-angiotensin system is an important modulator of arterial blood pressure and inhibitors of the angiotensin-converting enzyme (ACE-Is) and are currently used in the treatment of hypertension. The pleiotropic actions exerted by angiotensin II (AngII) on the functionality of the vessel wall may have pro-atherosclerotic outcomes; evidence for an anti-atherosclerotic effect of ACE-Is has been presented and an antioxidant effect has been attributed to thiol-containing ACE-Is, like Captopril. The present study has been undertaken to investigate the effect of Delapril, a lipophilic ACE-I, on the development of atherosclerosis in cholesterol-fed rabbits. While it did not correct hyperlipidemia, Delapril dose dependently inhibited the development of atherosclerosis, expressed as aortic area covered by lesions (23.3+/-4.1, 21.3+/-2.4 and 18.5+/-3.3% with Delapril at the daily dose of 5, 10 and 20 mg/kg, respectively, versus 38.2%+/-6.4 for control animals) and its effect was similar to that of Captopril (14.5+/-5.1% at the daily dose of 25 mg/kg). Furthermore, Delapril partially and dose dependently restored endothelium-dependent relaxation, which is impaired in vessels from hypercholesterolemic animals (51.80+/-12.18, 59.74+/-5.16, 69.13+/-8.70 maximal percent relaxation versus 48.26+/-3.05% for the untreated control and 67.67+/-6.72% for Captopril-treated animals). An antioxidant mechanism is unlikely to explain this data, since Delapril does not contain thiol groups. These observations suggest that Delapril may represent an effective pharmacological approach for the treatment of atherosclerosis during its early phases. |
| Delayed clearance of beta-very low density lipoprotein after feeding cholesterol to splenectomized rabbits Asai, K., T. Hayashi, et al. (1990), Artery 18(1): 32-46. Abstract: The role of the spleen on the metabolism of lipids in cholesterol-fed rabbits was evaluated. Rabbits were divided into two groups: splenectomized and control (sham-operated) groups. After the operation, all rabbits were fed a 1% cholesterol diet for 12 weeks and the changes in serum lipids were observed. In a separate experiment, a study of the clearance of 125I-labeled lipoproteins, including beta-migrating very-low density lipoprotein (beta-VLDL), low density lipoprotein (LDL), and acetoacetylated-LDL, was carried out in both groups of rabbits. After cholesterol feeding, all rabbits showed marked hyperlipidemia; however, the splenectomized animals showed a significantly higher level of serum total cholesterol, triglycerides, and phospholipids together with a lower level of high-density lipoprotein cholesterol. A lipoprotein clearance study showed that beta-VLDL was cleared more slowly from the plasma of the splenectomized rabbits than of the controls fed a 1% cholesterol diet. Without cholesterol feeding, beta-VLDL was cleared more rapidly, and to a similar extent in both groups. The plasma clearance of either LDL or acetoacetylated-LDL did not differ between the two groups. These findings suggest that the spleen may play a role in catabolizing the excessive beta-VLDL in rabbits with dietary-induced hyperlipidemia. |
| Delayed effects of early nutrition with cholesterol plus saturated or polyunsaturated fatty acids on intestinal morphology and transport function in the rat Thomson, A. B., M. Keelan, et al. (1993), Biochim Biophys Acta 1170(1): 80-91. Abstract: This study was undertaken to test the hypotheses that: (1) the fatty acid and/or cholesterol composition of a nutritionally adequate isocaloric semisynthetic diet given in early life has lasting consequences for intestinal nutrient uptake and morphology; and (2) early life feeding experiences with diets of varying fatty acid or cholesterol composition influence the ability of the intestine to adapt to an altered nutrient uptake in later life. Weanling female Sprague-Dawley rats were fed nutritionally adequate isocaloric semisynthetic diets enriched with beef tallow, beef tallow plus 1% cholesterol, fish oil or fish oil plus 1% cholesterol. Animals fed fish oil or fish oil plus cholesterol for 11 weeks had a lower food intake but greater weight gain than animals fed beef tallow or beef tallow plus cholesterol. The age of the animals influenced lipid and hexose uptake. The uptake of these nutrients could also be changed by the addition of cholesterol to the diet. This cholesterol-related effect depended on the type of fat in the diet (saturated vs. polyunsaturated). These changes in nutrient uptake were associated with but not necessarily explained by alterations in food intake, body weight gain, intestinal mucosal weight or surface area. Finally, these changes in nutrient uptake and morphology may or may not be reversible. We speculate that dietary lipids may affect the ability of the intestine to adapt to an altered nutrient intake in later life. |
| Delayed loss of cholesterol from a localized lipoprotein depot in apolipoprotein A-I-deficient mice Stein, O., Y. Dabach, et al. (1997), Proc Natl Acad Sci U S A 94(18): 9820-4. Abstract: The anti-atherogenic role of high density lipoprotein is well known even though the mechanism has not been established. In this study, we have used a novel model system to test whether removal of lipoprotein cholesterol from a localized depot will be affected by apolipoprotein A-I (apo A-I) deficiency. We compared the egress of cholesterol injected in the form of cationized low density lipoprotein into the rectus femoris muscle of apo A-I K-O and control mice. When the injected lipoprotein had been labeled with 3Hcholesterol, the t1/2 of labeled cholesterol loss from the muscle was about 4 days in controls and more than 7 days in apo A-I K-O mice. The loss of cholesterol mass had an initial slow (about 4 days) and a later more rapid component; after day 4, the disappearance curves for apo A-I K-O and controls began to diverge, and by day 7, the loss of injected cholesterol was significantly slower in apo A-I K-O than in controls. The injected lipoprotein cholesterol is about 70% in esterified form and undergoes hydrolysis, which by day 4 was similar in control and apo A-I K-O mice. The efflux potential of serum from control and apo A-I K-O mice was studied using media containing 2% native or delipidated serum. A significantly lower efflux of 3Hcholesterol from macrophages was found with native and delipidated serum from apo A-I K-O mice. In conclusion, these findings show that lack of apo A-I results in a delay in cholesterol loss from a localized depot in vivo and from macrophages in culture. These results provide support for the thesis that anti-atherogenicity of high density lipoprotein is related in part to its role in cholesterol removal. |
| Delayed postprandial retinyl palmitate and squalene removal in a patient heterozygous for apolipoprotein A-IFIN mutation (Leu 159-->Arg) and low HDL cholesterol level without coronary artery disease Gylling, H., H. Relas, et al. (1996), Atherosclerosis 127(2): 239-43. Abstract: A low HDL cholesterol level is frequently but not consistently associated with inefficient postprandial fat clearance. We studied triglycerides, retinyl palmitate and squalene and apolipoprotein B-48 after a fat loading test in one subject heterozygous for a novel point mutation of apolipoprotein A-I (A-IFIN, Leu 159-->Arg) and low HDL cholesterol level without coronary artery disease, and in 16 healthy controls with the same apolipoprotein E phenotype, 3/3, as the proband. HDL cholesterol and apolipoprotein A-I levels were 0.32 mmol/l and 57 mg/dl in the proband, and 1.29 +/- 0.12 mmol/l (mean +/- S.E.) and 126 +/- 4 mg/dl in the controls. The peak concentration for triglycerides in plasma, chylomicrons and VLDL occurred at 4 h both in the case and controls. However, the peak concentrations for retinyl palmitate and squalene in chylomicrons and VLDL were delayed to 12 h in the proband compared with 4 and 9 h in the controls. The peak of apolipoprotein B-48 occurred at 6 h in the proband and at 4 h in the controls, so that triglycerides, apolipoprotein B-48 and retinyl palmitate and squalene peaked differently. After 24 h, retinyl palmitate, squalene, and apolipoprotein B-48 had returned to the baseline levels. The results show for the first time an impaired postprandial lipoprotein removal in a case heterozygote with moderately low HDL cholesterol due to an apolipoprotein A-1 mutation not associated with coronary artery disease. |
| Delineation of molecular changes in intrahepatic cholesterol metabolism resulting from diminished cholesterol absorption Repa, J. J., S. D. Turley, et al. (2005), J Lipid Res 46(4): 779-89. Abstract: The absorption of cholesterol by the small intestine is a major route for the net entry of cholesterol into the body and can therefore affect the plasma low density lipoprotein-cholesterol (LDL-C) concentration. These studies used ezetimibe, a potent inhibitor of cholesterol absorption, to delineate the biochemical and molecular changes in intrahepatic metabolism and biliary lipid secretion when there is a major reduction in chylomicron cholesterol delivery to the liver. In female LDL receptor (LDLR)-deficient (LDLR-/-) mice fed a basal diet containing ezetimibe (0-10 mg/day/kg body weight), cholesterol absorption was reduced up to 91%, fecal neutral sterol excretion was increased up to 4.7-fold, and plasma total cholesterol concentrations decreased by up to 18%. Blocking cholesterol absorption prevented the accumulation of very low density lipoproteins and LDL in the circulation of LDLR-/- mice fed a lipid-rich diet. In female LDLR+/+ mice fed the lipid-rich diet with ezetimibe, the relative mRNA level for the LDLR in the liver was 2-fold greater than in matching mice given the lipid-rich diet alone. We conclude that in the mouse the reduction in plasma LDL-C levels induced by blocking cholesterol absorption reflects both a diminished rate of LDL-C production and a modest increase in hepatic LDLR expression. |
| Delineation of the role of pre-beta 1-HDL in cholesterol efflux using isolated pre-beta 1-HDL Sviridov, D., O. Miyazaki, et al. (2002), Arterioscler Thromb Vasc Biol 22(9): 1482-8. Abstract: OBJECTIVE: The role of pre-beta1-high density lipoprotein (pre-beta1-HDL) in cholesterol efflux was investigated by separating human plasma into purified pre-beta1-HDL and pre-beta1-HDL-deficient plasma by using a monoclonal antibody specifically reacting with pre-beta1-HDL. METHODS AND RESULTS: When compared with whole plasma, pre-beta1-HDL-deficient plasma was equally efficient in promoting cholesterol efflux from human skin fibroblasts and THP-1 human macrophage cells. When added at the same apolipoprotein A-I concentration, pre-beta1-HDL was less effective than whole plasma in promoting cholesterol efflux from fibroblasts but equally effective in promoting cholesterol efflux from THP-1 cells. However, pre-beta1-HDL-deficient plasma reconstituted with 16% pre-beta1-HDL was more active than whole plasma, demonstrating that pre-beta1-HDL does promote cholesterol efflux actively. The amount of cellular cholesterol present in reisolated pre-beta1-HDL was 1.5- to 2-fold greater after incubation of the cells with whole plasma than after incubation of the cells with pre-beta1-HDL-deficient plasma or plasma treated with the anti-pre-beta1-HDL antibody. However, the anti-pre-beta1-HDL antibody did not inhibit cholesterol efflux. CONCLUSIONS: We conclude that whereas pre-beta1-HDL is capable of taking up cellular cholesterol, its presence in plasma is not essential for cholesterol efflux, at least in vitro. Instead, pre-beta1-HDL may be the first product of apolipoprotein A-I lipidation during the formation of HDL but may not play a major role in transferring cellular cholesterol to HDL. |
| Delivery and pathway in MCF7 cells of DNA vectorized by cationic liposomes derived from cholesterol Cao, A., D. Briane, et al. (2000), Antisense Nucleic Acid Drug Dev 10(5): 369-80. Abstract: We have investigated the delivery and the pathway in tumoral MCF7 cells of DNA carried by liposomes prepared from (trimethyl aminoethane carbamoyl cholesterol iodide (TMAE-Chol), a cholesterol-based cationic lipid with a quaternary ammonium on the polar head. The structure of DNA-liposome complexes depends on the length of DNA and on the lipid-DNA charge ratio X. Spherical beads constitute fine structures of the observed complexes even when they appear as aggregates. For oligonucleotide transfer, dissociation from liposomes after transfection, penetration of the oligonucleotides into nuclei, and a long resident time were observed. For plasmid transfer, a correlation between the variation in the transfection level and the ultrastructure of complexes was demonstrated. The results showed a cellular route of lipid/plasmid complexes from the beginning by endocytosis, entrapped into endosomes, released by the latter until entry in the perinuclear area, and then penetration of plasmids inside the nuclei resulting in the observed expression of the beta-galactosidase gene. |
| delta 13C analysis of cholesterol preserved in archaeological bones and teeth Stott, A. W. and R. P. Evershed (1996), Anal Chem 68(24): 4402-8. Abstract: Cholesterol preserved in archaeological bones and teeth constitutes an important new source of palaeodietary information. A method is described here for the isotopic (delta 13C) determination of cholesterol employing a semiautomated sample preparation procedure and the technique of isotope ratio monitoring/gas chromatography/ mass spectrometry (irm/GC/MS). High-temperature gas chromatography (HT-GC) and high-temperature gas chromatography/mass spectrometry (HT-GC/MS) were used to identify the lipids and quantify the cholesterol present in the total lipid extracts. delta 13C values are then readily obtained from nanogram amounts (approximately 50 ng) of cholesterol resolved and determined directly by high-resolution capillary irm/GC/MS of trimethylsilylated total lipid extracts. The protocol developed allows effective processing of the large numbers of samples essential for palaeodietary determinations. Analytical precision and reproducibility have been assessed through multiple sampling of the same skeleton (femur, 9th century). Comparable delta 13C values have been obtained from different skeletal members from the same individual. The utility of the approach is demonstrated through a study of the delta 13C values of cholesterol isolated from sections of femoral bones of individuals excavated from cemeteries (dated Saxon to 18th century) at a coastal site in the U.K. The mean delta 13C value (-22.2 +/- 0.3/1000, sigma = 0.9) determined for cholesterol in 50 different individuals indicates a strong preference for marine foods by the members of the community extending back over the last approximately 1500 years. A minority of individuals exhibited delta 13C values as low as -26/1000, indicating preferences for terrestrial rather than marine foodstuffs. |
| Demographic and behavioural correlates of high density lipoprotein cholesterol. An international comparison between northern Italy and the United States Ferrario, M., G. C. Cesana, et al. (1992), Int J Epidemiol 21(4): 665-75. Abstract: Recently published results of longitudinal follow-up studies conducted in the US have identified high density lipoprotein (HDL)-cholesterol as an independent and strong predictive factor for coronary heart disease (CHD). Some inconsistencies in this association have been found when geographical comparisons were done, which could be explained by hypothesizing differences in population HDL-cholesterol determinants. We carried out a comparative analysis of demographic and behavioural correlates of HDL-cholesterol between Northern Italy and the US, two countries with well-known differences in CHD risk and HDL-cholesterol levels. The study was conducted on representative samples of these two countries (MONICA Project-Area Brianza for Northern Italy and NHANES II for the US) and used comparable methodologies for data collection and statistical analysis. Results indicate that gender, age, body mass, cigarette smoking and alcohol consumption are independently associated with HDL-cholesterol in both populations; physical activity is positively, but not significantly, associated with HDL-cholesterol mean levels, and education achievement is independently associated only in the American sample. The comparison of the magnitude of the multivariate regression coefficients between the two studies suggests similar functional relationships for most of the correlates considered. The small, albeit significant, discrepancies found for body mass and smoking status could be related either to some methodological inconsistencies between the two surveys, or to possible effects of other covariates, not available to be tested in this study, like dietary habits. Moreover, HDL-cholesterol mean level differences between populations could be also due to differences in the prevalence of the examined correlates. |
| Demonstration of a direct effect on hepatic acyl CoA: cholesterol acyl transferase (ACAT) activity by an orally administered enzyme inhibitor in the hamster Burrier, R. E., S. Deren, et al. (1994), Biochem Pharmacol 47(9): 1545-51. Abstract: Orally active inhibitors of acyl CoA:cholesterol acyl transferase (ACAT), such as Lederle CL277082 (LE), are known to reduce plasma and hepatic cholesteryl ester levels, although the mechanisms are not well understood. Several groups have reported the inhibition of cholesterol absorption upon oral ACAT inhibitor administration. In this study, we used 7-day dietary and drug treatments of hamsters to examine the possible effects of LE on hepatic ACAT. ACAT assays were performed using liver homogenates in the absence and presence of a saturating level of exogenously added cholesterol. LE (100 mg/kg/day) treatment of chow or 0.5% cholesterol-fed animals caused reductions in ACAT activity without additional cholesterol as compared with non-treated animals. When a saturating level of cholesterol was added to the assays, reductions in ACAT activity upon LE treatment of chow- or cholesterol-fed animals were also observed. Treatment of cholesterol-fed animals with cholestyramine in the diet reduced ACAT activity in the absence of added cholesterol. However, ACAT activities similar to those of non-treated animals were observed at a saturating level of cholesterol. This latter effect demonstrates that inhibition of cholesterol absorption reduces cholesterol delivery to the liver but does not reduce cholesterol esterifying capacity since cholestyramine is not absorbed and has no direct effect on the liver. The decreased ACAT activity in homogenates from LE-treated animals could also be mimicked in a dose-dependent manner by the addition of exogenous LE to liver homogenates from non-treated animals. These results indicate that hepatic ACAT activity is regulated by the availability of free cholesterol, and that orally administered LE has a direct effect on hepatic ACAT activity in the liver. In addition, the data are consistent with LE activity in the liver as being responsible, in part, for the reduced hepatic and plasma cholesteryl esters in treated animals. |
| Demonstration of an association among dietary cholesterol, central serotonergic activity, and social behavior in monkeys Kaplan, J. R., C. A. Shively, et al. (1994), Psychosom Med 56(6): 479-84. Abstract: Epidemiologic studies link plasma cholesterol reduction to increased mortality rates as a result of suicide, violence, and accidents. Deficient central serotonergic activity is similarly associated with violence and suicidal behavior. We investigated the relationship among dietary and plasma cholesterol, social behavior, and the serotonin system as a possible explanation for these findings. Juvenile cynomolgus monkeys (eight female and nine male) were fed a diet high in fat and either high or low in cholesterol. We then evaluated their behavior over an 8-month period. Plasma lipids and cerebrospinal fluid metabolites of serotonin, norepinephrine, and dopamine were assessed on two occasions, at 4 and 5.5 months after the initiation of behavioral observations. Animals that consumed a low-cholesterol diet were more aggressive, less affiliative, and had lower cerebrospinal fluid concentrations of 5-hydroxyindoleacetic acid than did their high-cholesterol counterparts (p <.05 for each). The association among dietary cholesterol, serotonergic activity, and social behavior was consistent with data from other species and experiments and suggested that dietary lipids can influence brain neurochemistry and behavior; this phenomenon could be relevant to our understanding of the increase in suicide and violence-related death observed in cholesterol-lowering trials. |
| Denervation and exercise effects on cholesterol content of chick pectoralis and gastrocnemii muscles Sharma, S. and R. K. Malhotra (1993), Indian J Exp Biol 31(5): 493-5. |
| Deoxycholate and cholate modulate the source of cholesterol substrate for bile acid synthesis in the rat Scheibner, J., M. Fuchs, et al. (1995), Hepatology 21(2): 529-38. Abstract: In the current study, the role of the supply of preformed and newly synthesized cholesterol for the feedback control of the synthesis of different bile acids and the secretion of biliary cholesterol was investigated. To define these cholesterol fluxes and the possibility of a different modulation by bile acids with different suppressive capacities, a continuous labeling with tritiated water was used in rats with an extracorporeal bile duct receiving intraduodenal infusions of taurocholate or taurocholate plus deoxycholate. After bile acid pool depletion (6 to 9 hours) total muricholate, cholate, and chenodeoxycholate synthesis was variably increased (24% to 93%) during an infusion of 304 mumol taurocholate/kg per hour. The increase in bile acid synthesis and biliary cholesterol output was predominantly due to the utilization of preformed (unlabeled) cholesterol. The addition of 52 mumol/kg per hour of deoxycholate to 258 mumol/kg per hour of taurocholate had a comparable effect. In the late period (30 to 54 hours), the taurocholate infusion had little impact on total muricholate and chenodeoxycholate synthesis but caused by a significant increase of the proportion from performed cholesterol. Both total cholate production and its synthesis from de novo (labeled) cholesterol was inhibited by 30% (P <.05) and 64% (P <.01), respectively. The secretion rate of total and de novo biliary cholesterol was higher (65% and 72%; P <.01) compared with controls. In comparison, the combined bile acid infusion led to a further increase of total muricholate synthesis (P <.05), which was again due to an enhanced synthesis from performed cholesterol (P <.001). Similar changes were observed in chenodeoxycholate. The more pronounced suppression of total cholate synthesis by 81% (P <.05) was due to a diminished cholate synthesis from both de novo cholesterol by 72% (P <.001) and preformed cholesterol by 91% (P >.05). We conclude that the modulation of the synthesis of the various primary bile acids in the rat differs and feedback regulation of cholate synthesis by taurocholate and deoxycholate is mediated by different mechanisms of control, including inhibition of cholesterol 7 alpha-hydroxylase, HMG-CoA reductase, and uptake of lipoprotein cholesterol. |