scholarly journals The hypocholesterolaemic effects of sitostanol in the guinea pig are in part related to changes in hepatic lipids and lipoprotein composition

2001 ◽  
Vol 85 (2) ◽  
pp. 165-172 ◽  
Author(s):  
Tripurasundari Ramjiganesh ◽  
Suheeta Roy ◽  
Jonathan C. McIntyre ◽  
Maria Luz Fernandez

To evaluate some of the mechanisms involved in the plasma cholesterol lowering of sitostanol (SI), male Hartley guinea pigs were fed diets containing cholesterol (0.25 g/100 g) and four doses of SI: either 0 (control), 0.75, 1.5 or 2.25 g/100 g. In addition a negative control (-C) group with dietary cholesterol (0.04 g/100 g) was included. Corn oil was used as the source of fat and the contribution of fat energy was 35 %. Plasma total cholesterol was 43, 49 and 53 % (P<0.0001) lower after SI intake compared to the control. Plasma LDL concentrations were 47, 53 and 61 % lower with increasing doses of SI. In addition, intake of SI resulted in 26–42 % lower hepatic total cholesterol. Hepatic esterified cholesterol and triacylglycerols were 32–60 % and 55–61 % lower after SI intake. SI intake resulted in favourable plasma and hepatic cholesterol concentrations similar to those in guinea pigs fed low levels of dietary cholesterol (-C). The LDL obtained from the control group had a higher number of molecules of free and esterified cholesterol than the SI groups. SI intake resulted in 69–71 % higher cholesterol excretion compared to the control. SI treatment enhanced the total faecal neutral sterol excretion by 54–58 % compared to control and by 70–76 % compared to the (-C) group. These results suggest that SI might have its hypocholesterolaemic effect by reducing cholesterol absorption, which results in lower concentration of cholesterol in liver. This reduction in hepatic cholesterol might possibly alter hepatic cholesterol metabolism and affect lipoprotein concentration and composition.

1985 ◽  
Vol 249 (3) ◽  
pp. E251-E256
Author(s):  
M. T. Subbiah ◽  
R. L. Yunker ◽  
A. Menkhaus ◽  
B. Poe

Premature weaning in animals causes higher serum cholesterol levels and a relative inability to handle cholesterol challenge in adult life. The mechanisms responsible for these delayed effects of premature weaning are not clear. The aims of this investigation were to 1) determine the effect of premature weaning on the activity of hepatic cholesterol 7 alpha-hydroxylase and plasma cholesterol changes and 2) determine whether addition of cholesterol to the diet will restore premature weaning-induced changes. Premature weaning did not prevent the phenomenon of neonatal hypercholesterolemia noted in day 5 of normally weaned guinea pigs. At day 10, prematurely weaned animals had lower serum cholesterol when compared with normally weaned animals. Premature weaning caused (without or with cholesterol in diet) a significant decrease in the hepatic activity of cholesterol 7 alpha-hydroxylase, and this difference persisted (after 1 mo) when fed the stock diet. These studies demonstrate 1) premature weaning on day 2 does not prevent neonatal hypercholesterolemia on day 5, 2) premature weaning causes a decrease in hepatic cholesterol 7 alpha-hydroxylase activity that persists into adult life, and 3) dietary cholesterol intake in early life is unable to negate premature weaning-induced changes.


2002 ◽  
Vol 132 (3) ◽  
pp. 335-340 ◽  
Author(s):  
Tripurasundari Ramjiganesh ◽  
Suheeta Roy ◽  
Hedley C. Freake ◽  
Jonathan C. McIntyre ◽  
Maria Luz Fernandez

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1272 ◽  
Author(s):  
Jung Kim ◽  
Wayne Campbell

Whole egg is a food source of dietary cholesterol and inconsistent research findings exist about the effect of dietary cholesterol from whole egg on blood cholesterol concentration. We assessed the effect of co-consuming cooked whole egg (CWE) on dietary cholesterol absorption from two randomized-crossover studies. For study 1, 16 men consumed raw vegetables with no egg, 75 g CWE, or 150 g CWE. For study 2, 17 women consumed cooked vegetables with no egg or 100 g CWE. Triacylglycerol-rich lipoprotein fractions (TRL) were isolated from collected blood. In study 1, total-cholesterol areas under the curve (AUC)0–10h in TRL were not different but triacylglycerol AUC0–10h in TRL was greater for 150 g CWE vs. 75 g CWE and no egg. Similarly, in study 2, total-cholesterol AUC0–10h in TRL was not different but triacylglycerol AUC0–10h in TRL was greater for 100 g CWE vs. no egg. In both studies, whole egg consumption did not affect plasma total-cholesterol AUC0–10h, while triacylglycerol AUC0–10h was increased. These results suggest that the dietary cholesterol in whole egg was not well absorbed, which may provide mechanistic insight for why it does not acutely influence plasma total-cholesterol concentration and is not associated with longer-term plasma cholesterol control.


2000 ◽  
Vol 11 (7-8) ◽  
pp. 358-366 ◽  
Author(s):  
Tripurasundari Ramjiganesh ◽  
Suheeta Roy ◽  
Robert J Nicolosi ◽  
Tracy L Young ◽  
Jonathan C McIntyre ◽  
...  

1993 ◽  
Vol 70 (3) ◽  
pp. 721-726 ◽  
Author(s):  
H. A. Van Lith ◽  
A. C. Beynen

The question addressed is whether an increased intake of cholesterol affects esterase-1 (EC3.1.1.1; ES-1) and butyrylcholinesterase (EC3.1.1.8) activity in plasma. Rats were fed on a purified diet either without or with cholesterol (10 g/kg) added at the expense of the carbohydrate source. Dietary cholesterol significantly decreased plasma butyrylcholinesterase activity, but raised plasma ES-1 activity. Evidence is discussed, suggesting that plasma butyrylcholinesterase is involved in plasma cholesterol metabolism, whereas esterase-1 is involved in intestinal cholesterol absorption.


1957 ◽  
Vol 106 (5) ◽  
pp. 727-742 ◽  
Author(s):  
Oscar W. Portman ◽  
Leonardo Sinisterra

A series of studies of cholesterol metabolism in the Cebus monkey were carried out in an attempt to understand the mechanisms responsible for the great differences in serum cholesterol levels when different dietary fats were used. Three groups of monkeys, one fed diets including 45 per cent of calories as corn oil, a second corn oil plus cholesterol (0.1 gm./100 calories), and a third lard plus cholesterol for 5 months (mean serum cholesterol values were 237, 268, and 601 mg. per cent, respectively) were injected with emulsions of cholesterol-4-C14. The mean biological half-lives for the disappearance of serum radiocholesterol were 8.8, 8.4, and 6.6 days respectively. Esterification of radiocholesterol as measured by equilibration of specific activities of serum-free cholesterol and total cholesterol was delayed in the monkeys fed lard plus cholesterol. When cholesterol-4-C-14-stearate was given intravenously to a series of monkeys, an erratic non-exponential biological decay curve resulted. Specific activity for free serum cholesterol was greater than that for total cholesterol within 1 hour after the injection. After 7 months on experimental diets including corn oil with added cholesterol and lard with added cholesterol the levels of lipides in most tissues were not different for the two dietary groups, nor were they appreciably elevated above previous control figures for monkeys not fed cholesterol. Total lipide levels in the adrenals of monkeys fed corn oil were twice those of monkeys fed lard. Monkeys were fasted before and after intragastric administration of cholesterol-4-C14 in small formula meals including various fats and fatty acids. The disappearance of total cholesterol from the serum consisted of a rapid followed by a slow exponential function. The type of fat and fatty acid appeared to influence the rate of disappearance of radiocholesterol. There was a broad range of apparent activity of the different fats and fatty acids in promoting cholesterol absorption.


2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Manya Warrier ◽  
Stepahie Marshall ◽  
Allison McDaniel ◽  
Martha Wilson ◽  
Amanda Brown ◽  
...  

Recent studies have revealed a novel route for cholesterol disposal through intestine known as transintestinal cholesterol efflux (TICE) that significantly contributes to fecal neutral sterol loss. This pathway is an integral part of reverse cholesterol transport (RCT), yet major mechanisms regulating TICE are not well understood. Using an unbiased transcriptional profiling approach in mouse models of augmented TICE, we found that hepatic expression of the enzyme Flavin monoxygenase 3 (FMO3) was dramatically repressed. At the same time we identified this enzyme through transcriptional profiling, it was reported that plasma levels of its product trimethylamineoxide (TMAO) are highly predictive of atheroslcerosis in humans, and TMAO is proatherogenic in mice. To further understand FMO3’s role as a regulator of cholesterol metabolism we used antisense oligonucleotides (ASO) to knockdown FMO3 expression in mouse liver in C57BL/6 mice fed either low (0.02%) or high (0.2%) levels of dietary cholesterol. As expected, FMO3 knockdown (>90% knockdown in the liver) increased the TMA/TMAO ratio in plasma more than 3-fold. Interestingly, knockdown of FMO biliary cholesterol levels were reduced by 60%, whereas fecal cholesterol loss was quite normal in FMO3 ASO treated mice fed a high cholesterol diet, which phenocopies a previously described mouse model where TICE predominates (NPC1L1-liver transgenic mice). ASO-mediated knockdown of FMO3 also unexpectedly reduced hepatic cholesteryl ester (CE) storage by 70% in mice fed 0.2% cholesterol. In parallel, knockdown of FMO3 reduces plasma VLDL cholesterol levels and the secretion rate of VLDL cholesteryl ester, but not triacylglycerol in cholesterol fed mice. FMO3 knockdown also reduced the hepatic expression of several liver X receptor (LXR) target genes, while increasing expression of genes involved in cholesterol synthesis. Collectively, these studies have identified FMO3 as a novel regulator of hepatic cholesterol metabolism and TICE. Given that plasma levels of FMO3’s product (TMAO) are strongly associated with atherosclerosis development in humans, and production of TMAO promotes atherosclerosis in mice, these studies have important implications for future cardiovascular drug discovery.


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