| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Influence of low high-density lipoprotein cholesterol on left ventricular hypertrophy and diastolic function in essential hypertension Horio, T., J. Miyazato, et al. (2003), Am J Hypertens 16(11 Pt 1): 938-44. Abstract: BACKGROUND: Left ventricular (LV) hypertrophy and LV diastolic dysfunction, which are common cardiac changes in hypertensive patients, are modified by several nonhemodynamic (eg, genetic, neurohumoral, and metabolic) factors. However, the influence of serum lipids on these LV changes has not been sufficiently studied. Although low high-density lipoprotein (HDL) cholesterol is well known to be a major risk factor for coronary heart disease, it is unclear whether HDL cholesterol plays a role in hypertensive heart disease. METHODS: In 274 patients with treated essential hypertension, two-dimensional and Doppler echocardiography were performed, and LV mass, ratio of peak velocity of atrial filling to early diastolic filling (A to E ratio A/E), and deceleration time of the E-wave were evaluated. The relationship of dyslipidemia, especially low HDL cholesterol, to LV hypertrophy and diastolic function was investigated in these patients. RESULTS: In a univariate regression analysis, HDL cholesterol was inversely associated with LV mass, A/E, and deceleration time. The association of HDL cholesterol with LV diastolic function was observed in both men and women. Its association with LV mass was gender-dependent, being significant only in women. Triglycerides were weakly correlated with LV mass and A/E, but total and low-density lipoprotein cholesterol had no correlations with these indices. In a multiple regression analysis, only low HDL cholesterol among several lipid levels was an independent predictor of both LV mass and LV diastolic dysfunction. CONCLUSIONS: Our findings suggest that low HDL cholesterol may unfavorably modify LV structure and diastolic function in patients with treated essential hypertension. |
| Influence of membrane cholesterol on modulation of the GABA(A) receptor by neuroactive steroids and other potentiators Sooksawate, T. and M. A. Simmonds (2001), Br J Pharmacol 134(6): 1303-11. Abstract: 1. The influence of membrane cholesterol on some pharmacological properties of the GABA(A) receptor was investigated in acutely dissociated rat hippocampal neurones with whole cell patch clamp recording. The cholesterol levels were varied between 56% and 235% control using methyl-beta-cyclodextrin as the cholesterol carrier. 2. Enrichment of neurones with cholesterol increased the effects of the non-steroidal GABA potentiators propofol, flunitrazepam and pentobarbitone. A similar result was obtained after pre-incubation of neurones with epicholesterol, the 3alpha-hydroxy isomer of cholesterol. 3. In contrast, the effects of the steroidal GABA potentiators pregnanolone and alfaxalone were reduced by cholesterol enrichment, but not by epicholesterol. Depletion of membrane cholesterol increased the potentiation of GABA by pregnanolone and alfaxalone but did not affect the non-steroidal potentiators. 4. The steroidal antagonist of GABA, pregnenolone sulphate, reduced the maximum response to GABA. This effect, also, was diminished in cholesterol-enriched neurones and enhanced in cholesterol-depleted neurones. 5. The effects of the cholesterol manipulations that were selective for the steroidal modulators of GABA are suggested to arise from direct interactions between membrane cholesterol and the GABA(A) receptor. The separate effects on the non-steroidal potentiators of GABA of cholesterol-enrichment or addition of epicholesterol to the neurones are suggested to be due to changes in membrane fluidity. 6. In view of the likely physiological modulation of GABA(A) receptors by endogenous neuroactive steroids and evidence of the in vivo lability of membrane cholesterol, the present observations may have physiological as well as pharmacological relevance. |
| Influence of membrane components on the stability and drug release properties of reverse phase evaporation vesicles (REVs): light sensitive all-trans retinal, negatively charged phospholipid dicetylphosphate and cholesterol Gursel, M. and V. Hasirci (1995), J Microencapsul 12(6): 661-9. Abstract: Incorporation of a negatively charged phospholipid, dicetylphosphate, initially increased encapsulation efficiency (from 12 to 24%) but beyond 5% (molar) a detrimental effect was observed. Rate of drug release from REVs was, for most cases, found to be bi-phasic implying partitioning between the lipid bilayer and the aqueous compartment. It was not possible to prepare liposomes with more than 1% (molar) all-trans retinal (ATR) as a membrane component. When ATR was reduced to 0.5% (molar), encapsulation efficiency increased to 7.76%. Upon exposure to long wave UV (365 nm), release from ATR containing REVs was increased and this was attributed to the formation of 13-cis isomer as indicated by HPLC and UV spectroscopy data. |
| Influence of menopause on blood cholesterol levels in women: the role of body composition, fat distribution and hormonal milieu. Virgilio Menopause Health Group Pasquali, R., F. Casimirri, et al. (1997), J Intern Med 241(3): 195-203. Abstract: OBJECTIVES: In this study we investigated the relationships between blood lipids and menopausal status. SETTING AND SUBJECTS: All data were obtained from the first cross-sectional examination of the Virgilio Menopause Health Project in a large cohort of middle-aged women in pre, peri-, and postmenopausal age. The data refer to 426 women without metabolic or endocrine diseases, relevant hepatic, renal and cardiovascular abnormalities, none were dieting or taking medications. MAIN OUTCOME MEASURES: A precoded questionnaire including full clinical history, socio-economic and personal information, habitual diet, physical activity, drug use and smoking habits, careful recording of gynaecological events and family history for disease was completed. Several anthropometric parameters and the bioelectrical impedance analysis was used to measure free fatty mass. Blood samples for hormones and biochemistry were also obtained. RESULTS: There were no significant differences on body mass index, fatty mass, free fatty mass and parameters of body fat distribution between the three groups. Again, there were no differences in smoking habits, dietary intake or indices of physical activity amongst the groups. There was a significant increase from pre to postmenopause of LH and FSH and a decrease of oestradiol and testosterone, whereas no difference was found in sex hormone-binding globulin. Age-adjusted values of glucose, triglycerides and high density lipoprotein (HDL-) cholesterol were similar in all groups, whereas postmenopausal women had significantly higher values of total and low density lipoprotein (LDL-) cholesterol. On the contrary, there was a significant fall in insulin levels passing from pre to postmenopause. In multiple regression models, total and LDL-cholesterol correlated positively with body mass index, waist-to-hip ratio and age, and negatively with free fatty mass and oestradiol blood levels. CONCLUSIONS: These results are consistent with the hypothesis that menopausal status may have a significant and independent effect in determining increased total and LDL-cholesterol concentrations in postmenopausal women. |
| Influence of menopause on high density lipoprotein-cholesterol and lipids Kim, C. J., T. H. Kim, et al. (2000), J Korean Med Sci 15(4): 380-6. Abstract: It has been generally accepted that high density lipoprotein cholesterol (HDL-C) level decreases with menopause in women. However, recent reports show different results. There is very little data concerning perimenopausal women. To verify these findings, lipids and lipoprotein(a) Lp(a) levels were compared among pre-, peri- and postmenopausal women of similar mean ages. Postmenopausal women had higher HDL-C levels than premenopausal women (p<0.001) and there was no difference between peri- and postmenopausal women. LDL-C level in perimenopausal women was lower than in postmenopausal women (p<0.001) and higher than in premenopausal women with borderline significance (p=.051). Total cholesterol levels showed stepwise elevation from premenopause to postmenopause. Perimenopausal women had lower Lp(a) levels than postmenopausal women (p<0.0005) and similar levels to premenopausal women. Lp(a) levels between 0.1 to 10.0 mg/dL were the most prevalent in pre- and perimenopausal women, and those between 10.1 to 20.0 mg/dL in postmenopausal women. In conclusion, menopause itself is associated with the elevation of HDL-C level, and the postmenopausal increase of coronary artery disease is not related to postmenopausal change of HDL-C level. Perimenopausal status, although transient, may favor Lp(a) and lipid profiles for delaying atherosclerosis. |
| Influence of mild to moderately elevated triglycerides on low density lipoprotein subfraction concentration and composition in healthy men with low high density lipoprotein cholesterol levels Halle, M., A. Berg, et al. (1999), Atherosclerosis 143(1): 185-92. Abstract: Epidemiologic studies have shown that a dyslipoproteinemia with low concentrations of high density lipoprotein (HDL) cholesterol and elevated serum triglycerides (TG) is associated with a particularly high incidence of coronary artery disease. This lipid profile is associated with increased concentrations of small, dense low density lipoprotein (LDL) particles. To evaluate the role of mild to moderately elevated TG on the LDL subfraction profile in patients with low HDL cholesterol, concentration and composition of six LDL subfractions was determined by density gradient ultracentrifugation in 41 healthy men (31+/-9 years, body mass index (BMI) 25.1+/-3.9 kg/m2) with equally low HDL cholesterol levels < 0.91 mmol/l but different TG levels: TG < 1.13 mmol/l, n = 16; TG = 1.13-2.26 mmol/l, n = 13: TG = 2.26-3.39 mmol/l, n = 12. Those men with moderately elevated TG levels between 2.26 and 3.39 mmol/l had significantly higher concentrations of very low density lipoprotein (VLDL), intermediate low density lipoprotein (IDL), and small, dense LDL apoB and cholesterol than men with TG < 1.13 mmol/l. With increasing serum TG, the TG content per particle also increased in VLDL, IDL as well as total LDL particles while the cholesterol and phospholipid (PL) content decreased in VLDL and IDL, but not in LDL particles. LDL subfraction analysis revealed that only large, more buoyant LDL particles (d < 1.044 g/ml) but not the smaller, more dense LDL, were enriched in TG. Small, dense LDL particles were depleted of free cholesterol (FC) and PL. This study has shown that in men with low HDL cholesterol levels mild to moderately elevated serum TG strongly suggest the presence of other metabolic cardiovascular risk factors and in particular of a more atherogenic LDL subfraction profile of increased concentration of small, dense LDL particles that are depleted in surface lipids. |
| Influence of mutation in human apolipoprotein A-1 gene promoter on plasma LDL cholesterol response to dietary fat Lopez-Miranda, J., J. M. Ordovas, et al. (1994), Lancet 343(8908): 1246-9. Abstract: The plasma lipid response to changes in dietary fat and cholesterol can vary between individuals. At present, responders cannot be identified in advance. An adenine to guanine (A-->G) mutation in the promoter of the apolipoprotein A1 gene (apoA-1) has been suggested as affecting plasma high-density lipoprotein cholesterol. In 50 young men we examined the effect of the same mutation on the responses of both high and low density lipoprotein cholesterol to low-fat diet. The frequency for the A allele was 0.14. Subjects were fed a low-fat diet for 25 days, followed by a diet rich in monounsaturated fatty acid (MUFA, 22% out of 40% fat) for 28 days and lipoproteins were measured at the end of each diet. There were no differences in initial total cholesterol between subjects with the G/G mutation (170 mg/dL: 100 mg/dL = 2.59 mmol/L) and the G/A mutation (169 mg/dL) genotypes. After consumption of the high monounsaturated fat diet, significant increases were noted in plasma LDL cholesterol (10 mg/dL, p = 0.035) in the G/A subjects but not in the G/G subjects (1 mg/dL, p = 0.996). These differences showed that a significant diet-gene interaction (p = 0.015) existed. No differences were observed on HDL cholesterol between groups. Plasma low-density lipoprotein cholesterol responsiveness to diet may be explained by variation at the apoA-I gene locus. |
| Influence of newly synthesized cholesterol on bile acid synthesis during chronic inhibition of bile acid absorption Bertolotti, M., L. Zambianchi, et al. (2003), Hepatology 38(4): 939-46. Abstract: The effects of newly synthesized cholesterol availability on bile acid synthesis are largely unknown, particularly in humans. The present study was aimed to study the changes induced on bile acid synthesis by simvastatin, a competitive inhibitor of hydroxymethyl glutaryl-CoA (HMG-CoA) reductase, the rate-limiting enzyme of cholesterol synthesis, during pharmacologic interruption of the enterohepatic circulation. Six patients with primary hypercholesterolemia were studied in basal conditions, after treatment with the bile acid binding resin cholestyramine alone (8-16 g/d for 6-8 weeks) and subsequently in combination with simvastatin (40 mg/d for 6-8 weeks). Cholesterol 7alpha-hydroxylation rate, a measure of total bile acid synthesis, was assayed in vivo by tritium release analysis. Serum lathosterol levels were assayed by gas chromatography-mass spectrometry as a measure of cholesterol synthesis. Serum total and low-density lipoprotein-cholesterol were reduced significantly after cholestyramine (by 26% and 30%, respectively) and during combined treatment (by 47% and 55%). 7alpha-hydroxylation rates increased nearly 4-fold with cholestyramine alone; addition of simvastatin induced a significant decrease of hydroxylation rates (cholestyramine alone, 1,591 +/- 183 mg/d; plus simvastatin, 1,098 +/- 232 mg/d; mean +/- SEM; P <.05). Hydroxylation rates significantly correlated with serum lathosterol/cholesterol ratio (r = 0.79, P <.05). In conclusion, in conditions of chronic stimulation bile acid synthesis may be affected by changes in newly synthesized cholesterol availability. The finding might relate to the degree of substrate saturation of microsomal cholesterol 7alpha-hydroxylase; alternatively, newly synthesized cholesterol might induce a stimulatory effect on cholesterol 7alpha-hydroxylase transcription. |
| Influence of nifedipine on aortal cholesterol content, blood coagulation and elastin metabolism in cholesterol-fed rabbits Klin, M. J., A. Wystrychowski, et al. (1992), Pol J Pharmacol Pharm 44(5): 461-8. Abstract: Our studies showed that the nifedipine in daily doses of 30 mg/kg given to rabbits treated with a diet containing 1% cholesterol for 6 months, decreased cholesterol content in aorta homogenates, urine excretion of desmosines and prolonged partial thromboplastin time, while it did not alter serum lipids. These results may have some value for understanding of the antiatherogenic mechanism of nifedipine. |
| Influence of nifedipine on stone formation and renal function in cholesterol-induced nephrolithiasis in rats Strohmaier, W. L., B. Witte, et al. (1994), Urol Int 52(2): 87-92. Abstract: Previous investigations showed that nifedipine limited calcium phosphate stone formation induced by a high-cholesterol diet in rats. This study was performed to obtain further insights into the effects of nifedipine on stone prevention, renal function and urine composition. Male Wistar rats were assigned to one of the following groups: (1) cholesterol diet (n = 22), (2) cholesterol diet plus nifedipine (n = 22) and (3) control (n = 6). A high-cholesterol diet was given for 4 weeks, nifedipine was administered by gavage to group 2 for 4 weeks (50 mg/kg/24 h). During weeks 1 and 4, 5 rats of each group were housed in metabolic cages for urine collection. Sodium (Na), calcium (Ca), magnesium (Mg), phosphate (P(i)), citrate and creatinine were determined in the urine. The kidneys of 4 animals of group 1 and 2 were perfused and removed for histology after 1, 2, 3 and 4 weeks, respectively. Clearance studies (inulin, Na, Ca, Mg, P(i)) were performed (n = 6/group) after 4 weeks. The cholesterol diet induced a marked renal stone formation which was significantly limited by nifedipine calcification index (week 4) 1.75 +/- 0.5 vs. 0.75 +/- 0.5. The sequential histological examinations showed that concrement formation started intracellularly after only 1 week in group 1, whereas in group 2 the first concretions were observed only after 3 weeks. The cholesterol diet induced an increased excretion of Ca and P(i) citrate and Mg were reduced. The concomitant application of nifedipine resulted in a higher excretion of Ca, Mg and citrate when compared to the cholesterol group. The inulin clearance was decreased in the latter group.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Influence of obesity and hypertriglyceridaemia on the low HDL2-cholesterol level and on its relationship with prevalence of atherosclerosis in type 2 diabetes Verges, B., J. M. Brun, et al. (1992), Diabete Metab 18(4): 289-97. Abstract: High density lipoprotein subfraction 2 (HDL1)-cholesterol level is usually decreased in Type 2 (non-insulin-dependent) diabetes. A study was carried out in 251 Type 2 diabetic patients (106 males M, 145 females F) and in 120 non diabetic controls in order to determine the influence of hypertriglyceridaemia and obesity on the HDL2-cholesterol level and to analyse the relationship between HDL2-cholesterol level and atherosclerosis (coronary heart disease, peripheral atherosclerosis or cerebral vascular disease), in Type 2 diabetes. Influence of hypertriglyceridaemia and obesity on HDL2-cholesterol level was studied by comparing the mean values of HDL2-cholesterol between diabetics and controls, after controlling for hypertriglyceridaemia and obesity, and by a multiple linear regression test. A stepwise logistic regression was performed to analyse the association between the prevalence of atherosclerosis and several variables: age, duration of diabetes, hypertension, cigarette smoking, body mass index, mean glycaemia, total cholesterol, triglyceride, HDL-cholesterol, HDL2-cholesterol and HDL3-cholesterol levels. In both men and women, when both of the factors (hypertriglyceridaemia and obesity) were present of when only one was, HDL2-cholesterol level was significantly lower in the diabetic population, compared with controls. But when obesity and hypertriglyceridaemia were absent, HDL2-cholesterol level, in the diabetic population, was not significantly different from controls (M: 17.9 +/- 13.3 vs 20.5 +/- 13.8 mg/dl: NS; F: 30.1 +/- 21.5 vs 27.6 +/- 14.2 mg/dl: NS).(ABSTRACT TRUNCATED AT 250 WORDS) |
| Influence of orally and rectally administered propionate on cholesterol and glucose metabolism in obese rats Berggren, A. M., E. M. Nyman, et al. (1996), Br J Nutr 76(2): 287-94. Abstract: It has increasingly been suggested that the short-chain fatty acids (SCFA) acetic, propionic and butyric acids, derived from colonic fermentation of dietary fibre and other indigestible carbohydrates, exert different physiological effects. Formation of propionic acid is discussed in terms of beneficial effects on glucose and cholesterol metabolism. The aim of the present study was to evaluate possible metabolic effects of propionic acid and to differentiate between effects mediated in the upper gastrointestinal tract and those mediated in the hind-gut. For this purpose, obese hyperinsulinaemic (fa/fa) rats were studied during a 19 d test period. Sodium propionate was either fed orally through the diet (1 g/d), or infused rectally (0.15 g/d) to animals given diets high in cholesterol (20 g/kg) and saturated fat (130 g/kg). At the end of the test period total liver cholesterol pools were 20% lower (P < 0.01) in rats given dietary or rectally infused propionate (481 and 484 mg respectively) compared with the control group (614 mg). This was due to lower liver weights (P < 0.05) in propionate-treated animals, 15.5 and 15.3 g, v. 18.2 g in the control group, and no differences were noted in hepatic cholesterol concentrations. The urinary glucose excretion was measured during days 15-19 and was found to be lower (P < 0.05) in rats fed with propionate (23 mg) compared with the control group or the group infused rectally (39 and 38 mg respectively). In addition, fasting plasma glucose concentrations decreased significantly (P < 0.05) over the test period. It is concluded that orally supplied propionate affects both glucose and cholesterol metabolism as judged from lowered urinary glucose excretion, fasting blood glucose and liver cholesterol pools. On the other hand, propionate administered to the hind-gut at a physiologically relevant level reduces the hepatic cholesterol pool. |
| Influence of orotic acid on performance, liver lipid content, and egg cholesterol level of laying hens Beyer, R. S. and L. S. Jensen (1991), Poult Sci 70(11): 2322-8. Abstract: Three experiments were conducted to determine the effects of dietary orotic acid (OA) on laying hen performance, liver lipid content, and plasma and egg cholesterol levels. Laying hens were fed a basal diet supplemented with 0.5, 1.0, and 2.0% OA for 8 wk. Performance of the hens and cholesterol levels were measured at biweekly intervals. In all three experiments, OA decreased (P less than.05) BW in a linear manner. In two experiments, OA caused a linear decrease in total liver lipid (P less than.05), and in a third experiment OA resulted in a quadratic effect (P less than.01) on liver lipid content. There were no effects observed by OA supplementation on egg weight, yolk weight, percentage yolk, or egg production. Orotic acid failed to influence egg cholesterol content in any of the biweekly measurements of the three experiments. In two experiments, total plasma cholesterol content was not influenced by OA supplementation. Orotic acid significantly reduced (P less than.05) free and total plasma cholesterol in a third experiment when measured at Weeks 4, 6, and 8 of the experiment. The data indicate that OA is an ineffective dietary supplement for reducing egg cholesterol levels in laying hens. |
| Influence of personality traits on plasma levels of cortisol and cholesterol LeBlanc, J. and M. B. Ducharme (2005), Physiol Behav 84(5): 677-80. Abstract: The literature reports many organic malfunctions that are associated with elevated plasma cortisol and cholesterol levels. The present investigation was concerned with the influence of personality on plasma levels of cortisol and cholesterol. To that effect these variables were determined in a group of 20 subjects who answered the Big-Five Inventory for measurements of personality traits. It was found that: among the 5 personality traits, extraversion was positively correlated to plasma levels of cortisol and cholesterol while the correlation was negative for neuroticism. The positive correlation between extraversion and plasma cortisol and cholesterol, as well as with the responses to stress as shown in a previous study, are similar to findings previously reported on type A individuals. Further studies are needed with a larger group of subjects to conclude to a direct causal relationship between extraversion and the high levels of plasma cortisol and cholesterol, or a predisposition to some organic malfunctions as is the case for type A. |
| Influence of phospholipid unsaturation on the cholesterol distribution in membranes Pasenkiewicz-Gierula, M., W. K. Subczynski, et al. (1991), Biochimie 73(10): 1311-6. Abstract: Over the last half decade, we have studied saturated and unsaturated phosphatidylcholine (PC)-cholesterol membranes, with special attention paid to fluid-phase immiscibility in cis-unsaturated PC-cholesterol membranes. The investigations were carried out with fatty acid and sterol analogue spin labels for which reorientational diffusion of the nitroxide was measured using conventional ESR technique. We also used saturation recovery ESR technique where dual probes were utilized. Bimolecular collision rates between a membrane-soluble square-planar copper complex,3-ethoxy-2-oxobutyraldehyde bis(N4,N4-dimethylthiosemicarbazonato)copper(II) (CuKTMS2) and one of several nitroxide radical lipid-type spin labels were determined by measuring the nitroxide spin-lattice relaxation time (T1). The results obtained in all these studies can be explained if the following model is assumed: 1) at physiological temperatures, fluid-phase micro-immiscibility takes place in cis-unsaturated PC-cholesterol membranes, which induces cholesterol-rich domains in the membrane due to the steric nonconformability between the rigid fused-ring structure of cholesterol and the 30 degrees bend at the cis double bond of the alkyl chains of unsaturated PC. 2) The cholesterol-rich domains are small and/or of short lifetime (10(-9) s to less than 10(-7) s). Our results also suggest that the extra space that is available for conformational disorder and accommodation of small molecules is created in the central part of the bilayer by intercalation of cholesterol in cis-unsaturated PC membrane due to the mismatch in the hydrophobic length and nonconformability between cis-unsaturated PC alkyl chains and the bulky tetracyclic ring of cholesterol. |
| Influence of physical work on high density lipoprotein cholesterol: implications for the risk of coronary heart disease Sagiv, M. and U. Goldbourt (1994), Int J Sports Med 15(5): 261-6. Abstract: Physically trained individuals differ greatly from untrained counterparts in their high density lipoprotein (HDL) cholesterol blood levels. Such differences in turn may have implications for long-term preventive policies in coronary artery disease. In prospective studies, exercise programs in men, but seldom in women, have been shown to independently raise HDL cholesterol (HDL-C) concentrations in the blood. This evidence is of major interest because of the voluminous epidemiologic evidence for low blood levels of HDL-C as a risk factor for coronary heart disease. Experimental evidence is still missing to establish the efficacy of elevating blood HDL-C concentrations in actually reducing the risk of incident, or recurrent, coronary events. If the efficacy of elevating blood levels of HDL-C in ameliorating coronary prognosis is demonstrated, the recommendation for hygienic means, primarily physical exercise, will be reinforced. The role of physical training in elevating blood HDL-C is examined and plausible mechanisms for the observed experimental results are reviewed. |
| Influence of phytostanol phosphoryl ascorbate (FM-VP4) on insulin resistance, hyperglycemia, plasma lipid levels, and gastrointestinal absorption of exogenous cholesterol in Zucker (fa/fa) fatty and lean rats Wasan, K. M., C. Zamfir, et al. (2003), J Pharm Sci 92(2): 281-8. Abstract: The purpose of this investigation was to determine the effects of Phytostanol Phosphoryl Ascorbate (FM-VP4) on insulin resistance, hyperglycemia, plasma lipid levels, body weight, and gastrointestinal absorption of exogenous cholesterol in Zucker (fa/fa) fatty and lean rats. A group of 12 age-matched male obese (n = 6) and lean (n = 6) Zucker rats were administered 250 mg/kg twice a day (as 2% FM-VP4 in drinking water) for 30 consecutive days. Fasted blood samples prior to and following treatment were taken from all rats for glucose, lipid, insulin, and leptin determination. An oral glucose tolerance test was also carried out at the end of the treatment protocol. In addition, male obese (n = 7) and lean (n = 8) Zucker rats were coadministered a single oral gavage of (3)Hcholesterol plus cold cholesterol with or without FM-VP4 (20 mg/kg) dissolved in Intralipid and the plasma concentration of the radiolabel was determined 10 h following the dose. FM-VP4 30-day treatment did not alter body weight, morning glucose, insulin, lipids, and leptin concentrations. There was no alteration in glucose tolerance in the nondiabetic, normoglycemic lean group; however, there was a highly significant improvement in glucose tolerance in the fatty group following FM-VP4 treatment. In addition, the insulin response to oral glucose showed no significant change in nondiabetic lean rats, whereas there was a change in the insulin secretory profile in the fatty group following FM-VP4 treatment. Furthermore, following a single oral gavage of FM-VP4 resulted in a significant decrease in the percentage of radiolabeled cholesterol absorbed. These findings suggest that FM-VP4 treatment to fatty Zucker rats could result in increased glucose responsiveness of the insulin secreting pancreatic beta cells. Furthermore, our findings suggest that FM-VP4 may only be effective presystemically. Systemic administration of FM-VP4 is warranted to determine the therapeutic potential of this effect. |
| Influence of phytostanol phosphoryl ascorbate, FM-VP4, on pancreatic lipase activity and cholesterol accumulation within Caco-2 cells Ramaswamy, M., E. Yau, et al. (2002), J Pharm Pharm Sci 5(1): 29-38. Abstract: PURPOSE: The objective of this study was to determine how a novel hydrophilic phytostanol (FM-VP4) affects the cellular accumulation of 3Hcholesterol in human colon carcinoma (Caco-2) cell monolayers grown in Transwell chambers. METHODS: To determine cellular accumulation of cholesterol and FM-VP4, 3Hcholesterol- containing micelles (50 microM cholesterol containing 1.27x10 (-4)% 3Hcholesterol) or 3HFM-VP4 (50 microM) was incubated on the apical side of differentiated Caco-2 cell monolayers for 1 to 4 h at 37 degrees C in the absence or presence of increasing concentrations (10-200 microM) of unlabeled FM-VP4 or cholesterol, respectively. RESULTS: The accumulation of 3Hcholesterol (presented in micelles) into Caco-2 cell monolayers in the presence of 50 microM FM-VP4 was significantly lower (33.7 +/- 7.0%) compared to control (59.8 +/- 5.2%, p<0.05) following 4 h of incubation. Conversely, cholesterol inhibited the accumulation of 3HFM-VP4, although to a lesser extent, suggesting competition for binding sites. The inhibitory effects of FM-VP4 and cholesterol on each other were detectable after 1 h of incubation and increased with time. The extent of FM-VP4 inhibition of 3Hcholesterol accumulation was consistent whether FM-VP4 was co-incorporated into micelles or added separately in solution, suggesting that FM-VP4 does not elicit its effects through inhibition of cholesterol incorporation into micelles. In addition, pancreatic lipase activity (3Htriolein hydrolysis) and p-glycoprotein (rhodamine 123 fluorescence) activity, were not affected by FM-VP4. CONCLUSIONS: In conclusion, FM-VP4 rapidly inhibits cholesterol accumulation within Caco-2 cell monolayers in a mode independent of pancreatic lipase activity, p-glycoprotein activity or cholesterol incorporation in micelles. |
| Influence of plasma triglyceride and plasma cholesterol levels on the clearance rate of fibrinogen Verschuur, M., M. Bekkers, et al. (2001), Ann N Y Acad Sci 936: 639-42. Abstract: Increased plasma levels of fibrinogen are associated with a higher risk of cardiovascular disease. It has been suggested that lipid levels may influence the fibrinogen levels by a mechanism other than the synthesis rate, for example a decreased clearance rate. We performed a pilot study to explore this possibility. Twelve male Wistar rats were fed for four weeks with a control low fat/low cholesterol diet, a high fat/high cholesterol diet, and a high fat/high cholesterol diet with an additional 0.5% cholic acid. Labeled 125I fibrinogen was injected, and blood was sampled repeatedly. From the plasma radioactivity of the samples, fibrinogen halflife time was calculated for each animal. Our results suggest that plasma lipids lengthen the fibrinogen halflife times, although the differences were not statistically significant in this small study. Our final conclusion from this study is that lipids may have an effect on the turnover rate of fibrinogen and possibly affect fibrinogen levels through this mechanism. |
| Influence of pravastatin on hepatic metabolism of cholesterol Hellerstein, M. (1991), N Engl J Med 324(2): 128. |