ABILITY OF STARVATION AND OF DIETARY CHOLESTEROL TO SUPPRESS INCORPORATION OF LABELLED PRECURSORS INTO CHICK LIVER AND PLASMA CHOLESTEROL

1964 ◽  
Vol 42 (4) ◽  
pp. 443-449 ◽  
Author(s):  
P. J. Lupien ◽  
B. B. Migicovsky
Keyword(s):  
Cholesterol Synthesis ◽  
Plasma Cholesterol ◽  
Dietary Cholesterol ◽  
Liver Cholesterol ◽  
Acetate Incorporation ◽  
Cholesterol Feeding ◽  
Normal Rat ◽  
Do So

The effect of cholesterol feeding and of starvation on C14-acetate and mevalonate-2-C14 incorporation into serum and liver cholesterol of chicks, as well as the presence or absence of an inhibitor of cholesterol synthesis (I.C.S.) in cholesterol-fed rats, has been studied.Starvation significantly reduced C14-acetate incorporation into liver cholesterol of 15-day-old chicks, but did not affect mevalonate-2-C14 incorporation.The feeding of 1% dietary cholesterol significantly decreased both C14-acetate and mevalonate-2-C14 incorporation into liver cholesterol of the chick.Mitochondria from the livers of starved rats inhibited C14-acetate incorporation into liver cholesterol to a much greater extent than did "cholesterol-fed" or "normal" rat mitochondria.It is suggested that although starvation and cholesterol feeding both reduce the degree of acetate incorporation into cholesterol, they do so in different ways.

EFFECTS OF PYRIDOXINE DEFICIENCY AND DIETARY CHOLESTEROL SUPPLEMENTATION IN THE CHICK ON PLASMA PROTEIN-BOUND IODINE, GLUTAMIC–OXALACETIC TRANSAMINASE ACTIVITY, AND 14C-ACETATE INCORPORATION INTO CHOLESTEROL

1966 ◽  
Vol 44 (5) ◽  
pp. 625-633 ◽  
Author(s):  
P. J. Lupien
Keyword(s):  
Specific Activity ◽  
Plasma Cholesterol ◽  
Dietary Cholesterol ◽  
Experimental Period ◽  
Liver Cholesterol ◽  
Vitamin B ◽  
Acetate Incorporation ◽  
Glutamic Oxalacetic Transaminase ◽  
Pyridoxine Deficiency ◽  
Cholesterol Levels

The influence of B6 avitaminosis and the feeding of cholesterol on protein-bound iodine (PBI) of plasma and plasma glutamic–oxalacetic transaminase (PGOT) levels of chicks was studied, and the findings related to relative rates of 14C-acetate incorporation into plasma and liver cholesterol of chicks 3, 5, 11, and 15 days old.High plasma cholesterol levels were noted in the 11-day-old vitamin B6-deficient chicks. Liver cholesterol levels of this group were not significantly altered. Dietary cholesterol added at a level of 1% significantly increased liver and plasma cholesterol levels of the cholesterol-fed control and vitamin B6-deficient chicks; it also inhibited 14C-acetate incorporation into plasma and liver cholesterol to a much greater extent than did simple B6 avitaminosis or exogenous cholesterol per se. PBI parameters for control and vitamin B6-deficient chicks resembled those of plasma and liver cholesterol specific activity curves during the experimental period. Decreased PBI levels were noted 8 days after the beginning of the experiment in the vitamin B6-deficient birds. Dietary cholesterol significantly decreased PBI levels of 11-day-old control birds but increased it markedly 4 days later. PBI levels of the 11-day-old cholesterol-fed birds deficient in vitamin B6 were not changed, but were significantly increased 4 days later. PGOT levels were highest in 3-day-old control birds, and decreased rapidly thereafter. PGOT levels of the vitamin B6-deficient chicks were significantly decreased 3 to 4 days after the beginning of the experiment. The supplementary dietary cholesterol increased PGOT levels of 15-day-old cholesterol-fed control birds, but decreased PGOT levels of cholesterol-fed chicks deficient in vitamin B6. Although preliminary, these observations suggest an interrelationship between pyridoxine, thyroxine, and the mechanism responsible for the synthesis of cholesterol.

High plasma cholesterol in drug-induced cholestasis is associated with enhanced hepatic cholesterol synthesis

1999 ◽  
Vol 276 (5) ◽  
pp. G1165-G1173 ◽  
Author(s):  
Jeffrey W. Chisholm ◽  
Patrick Nation ◽  
Peter J. Dolphin ◽  
Luis B. Agellon
Keyword(s):  
Bile Acids ◽  
Cholesterol Synthesis ◽  
Cell Membranes ◽  
Reductase Activity ◽  
Plasma Cholesterol ◽  
Hepatic Cell ◽  
Plasma Lipoproteins ◽  
Liver Cholesterol ◽  
Hepatic Cholesterol ◽  
Hepatic Cholesterol Synthesis

In α-naphthylisothiocyanate-treated mice, plasma phospholipid (PL) levels were elevated 10- and 13-fold at 48 and 168 h, respectively, whereas free cholesterol (FC) levels increased between 48 h (17-fold) and 168 h (39-fold). Nearly all of these lipids were localized to lipoprotein X-like particles in the low-density lipoprotein density range. The PL fatty acyl composition was indicative of biliary origin. Liver cholesterol and PL content were near normal at all time points. Hepatic hydroxymethylglutaryl CoA reductase activity was increased sixfold at 48 h, and cholesterol 7α-hydroxylase activity was decreased by ∼70% between 24 and 72 h. These findings suggest a metabolic basis for the appearance of abnormal plasma lipoproteins during cholestasis. Initially, PL and bile acids appear in plasma where they serve to promote the efflux of cholesterol from hepatic cell membranes. Hepatic cholesterol synthesis is then likely stimulated in the response to the depletion of hepatic cell membranes of cholesterol. We speculate that the enhanced synthesis of cholesterol and impaired conversion to bile acids, particularly during the early phase of drug response, contribute to the accumulation of FC in the plasma.

scholarly journals Effect of dietary methionine on plasma and liver cholesterol concentrations in rats and expression of hepatic genes involved in cholesterol metabolism

2006 ◽  
Vol 95 (5) ◽  
pp. 879-888 ◽  
Author(s):  
F. Hirche ◽  
A. Schröder ◽  
B. Knoth ◽  
G. I. Stangl ◽  
K. Eder
Keyword(s):  
Cholesterol Synthesis ◽  
Cholesterol Metabolism ◽  
Plasma Cholesterol ◽  
Rat Hepatocytes ◽  
Liver Cholesterol ◽  
Isolated Rat Hepatocytes ◽  
Hepatic Expression ◽  
Hepatic Cholesterol Synthesis ◽  
Methionine Concentration ◽  
Ldl Uptake

Methionine has been shown to increase plasma cholesterol in animals. In the present study, mechanisms were investigated by which methionine could alter cholesterol metabolism. In the first experiment, forty growing rats were fed four casein-based diets differing in methionine content (2·6, 3·5, 4·5 or 6·0 g/kg) for 14 d. In the second experiment, isolated rat hepatocytes were incubated in media supplemented with 50, 100 or 200 μmol/l methionine. Dietary methionine tended to increase plasma homocysteine concentrations in the rats (P=0·058). A weak positive correlation between circulating homocysteine and plasma cholesterol was observed (R20·27, P<0·01). Rats fed 3·5 g/kg or more of methionine had higher concentrations of cholesterol in their plasma, in lipoprotein fractions of density (ρ kg/l) 1·006 < ρ<, 1·063 and ρ>. 1·063, and in liver than rats fed 2·6 g/kg methionine. Rats fed 6 g/kg methionine had a higher hepatic expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol-7α-hydroxylase than rats fed less methionine. The phosphatidylcholine:phosphatidylethanolamine ratio in rat liver increased with rising dietary methionine concentration; the relative mRNA concentrations of phosphatidylethanolamine N-methyltransferase and cystathionine β-synthase remained unaffected. Hepatocytes incubated in media supplemented with 100 or 200 μmol/l methionine had a higher cholesterol synthesis than hepatocytes incubated in a medium supplemented with 50μmol/l methionine; the LDL uptake in hepatocytes was independent of the methionine concentration of the medium. In conclusion, the present study suggests that dietary methionine induces hypercholesterolaemia at least in part via an enhanced hepatic cholesterol synthesis.

Localization of cholesterol synthesis in the small intestine of diabetic rats

1984 ◽  
Vol 247 (5) ◽  
pp. G494-G501
Author(s):  
K. R. Feingold ◽  
A. H. Moser
Keyword(s):  
Diabetes Mellitus ◽  
Small Intestine ◽  
Food Intake ◽  
Cholesterol Synthesis ◽  
Diabetic Rats ◽  
Cholesterol Feeding ◽  
Small Intestinal ◽  
Stimulation Of ◽  
Do So

Previous studies have demonstrated that cholesterol synthesis is increased twofold in the small intestine of diabetic animals. The present study demonstrates that the stimulation of small intestinal cholesterol synthesis by diabetes is a generalized phenomenon occurring in all segments of the small intestine. Quantitatively, in control animals the proximal two segments of the small intestine account for the majority of the total small intestinal cholesterol synthesis, whereas in the diabetic animals, because of the generalized stimulation in cholesterogenesis, the contribution of the terminal segments to total small intestinal cholesterol synthesis is of increased importance. The various manipulations that regulate cholesterol synthesis in the small intestine of diabetic animals also affect cholesterol synthesis in all portions of the small intestine. In diabetic animals cholesterol feeding and the limitation of food intake decrease cholesterol synthesis in the total small intestine and in all segments of the small intestine. Conversely, colestipol feeding increases cholesterol synthesis in all segments of the small intestine. These results demonstrate that, despite the obvious structural, functional, and environmental differences among the various segments of the small intestine, the stimulation of cholesterol synthesis that occurs secondary to diabetes mellitus is a generalized phenomenon. Similarly, the factors that regulate small intestinal cholesterol synthesis do so in a generalized manner.

Agents affecting lipid metabolism. XXXII. Effect of a liver mitochondrial extract on cholesterol synthesis in the rat

1968 ◽  
Vol 46 (2) ◽  
pp. 189-191
Author(s):  
M. N. Cayen ◽  
P. Hill ◽  
D. Dvornik
Keyword(s):  
Body Weight ◽  
Lipid Metabolism ◽  
Crude Extract ◽  
Cholesterol Synthesis ◽  
Liver Mitochondria ◽  
Liver Cholesterol ◽  
Acetate Incorporation ◽  
Hepatic Cholesterol ◽  
Experimental Conditions ◽  
Mitochondrial Extract

A lyophilized extract was prepared from liver mitochondria of rabbits starved for 24 h. Rats were fed single oral (1–4 g/kg body weight) and intraperitoneal (1.5 g/kg) doses of the crude extract. After 3 h, the livers of one group were removed and 2-14C-acetate incorporation into cholesterol was measured. In the second group, rats received an interperitoneal dose of 2-14C-acetate 1 h after administration of the mitochondrial extract; animals were sacrificed 2 h later and the incorporation into hepatic cholesterol was measured. Under these experimental conditions, administration of the mitochondrial extract did not decrease the incorporation of 2-14C-acetate into liver cholesterol.

Dietary Cholesterol Feeding Suppresses Human Cholesterol Synthesis Measured by Deuterium Incorporation and Urinary Mevalonic Acid Levels

1996 ◽  
Vol 16 (10) ◽  
pp. 1222-1228 ◽  
Author(s):  
Peter J.H. Jones ◽  
Anuradha S. Pappu ◽  
Lauren Hatcher ◽  
Zi-Chi Li ◽  
D. Roger Illingworth ◽  
...  
Keyword(s):  
Cholesterol Synthesis ◽  
Dietary Cholesterol ◽  
Mevalonic Acid ◽  
Cholesterol Feeding ◽  
Deuterium Incorporation

scholarly journals Hypercholesterolemia in the Rabbit Induced by Feeding Graded Amounts of Low-Level Cholesterol

1996 ◽  
Vol 16 (12) ◽  
pp. 1454-1464 ◽  
Author(s):  
Frank D. Kolodgie ◽  
Andrew S. Katocs ◽  
Elwood E. Largis ◽  
Simeon M. Wrenn ◽  
J. Fredrick Cornhill ◽  
...  
Keyword(s):  
Plasma Cholesterol ◽  
Dietary Cholesterol ◽  
Target Lesion ◽  
Individual Variability ◽  
Critical Parameters ◽  
Cholesterol Feeding ◽  
Time Curve ◽  
Coronary Artery Atherosclerosis ◽  
Atheromatous Plaques ◽  
Cholesterol Intake

While a number of studies have presented detailed examinations of lesion development in the cholesterol-fed rabbit, individual variability in response to cholesterol feeding and type of lesion produced relative to the degree of cholesterol exposure is not well defined. This study analyzed such critical parameters in an attempt to further characterize the model and establish a baseline for future testing of treatments targeted at limiting atherosclerosis. For these experiments, male New Zealand White rabbits were fed atherogenic diets consisting of 0.05%, 0.10%, 0.15%, 0.20%, or 0.25% cholesterol dissolved in 6% peanut oil for 31 to 32 weeks. Raising dietary cholesterol from 0.05% to 0.15% resulted in a less than twofold stepwise increase in total plasma cholesterol (TPC) exposure (area under plasma cholesterol versus time curve), whereas further increases in cholesterol intake resulted in an exponential four- to fivefold increase in TPC exposure. Regression analysis of TPC exposure with aortic sudanophilia demonstrated a threshold of ≈5000 cholesterol weeks; below this limit lesions were minimal, and above this value, the degree of plaque correlated with TPC exposure. Furthermore, a wide biological variability occurred among rabbits with respect to individual responsiveness to dietary cholesterol. In the aorta, various types of plaques, from fatty streaks to atheromatous lesions, were observed, depending on the degree of cholesterol intake. Diets consisting of <0.15% cholesterol resulted in the development of fatty streak lesions, while transitional lesions and atheromatous plaques were mostly found with higher cholesterol feeding. Coronary artery atherosclerosis was present in >50% of animals fed diets ≥0.15% cholesterol. Despite the level of TPC exposure, coronary lesions in epicardial vessels were generally the fibrous type, whereas intramyocardial arteries demonstrated predominantly intimal foam cells. In conclusion, by adjusting dietary cholesterol intake and selecting rabbits with a similar responsiveness to cholesterol, the overall cholesterol exposure can be more closely controlled to minimize the inherent individual variability among animals in this model. The nature of the target lesion must also be carefully considered, because the efficacy of some treatments may depend on the type of atherosclerotic plaque.

scholarly journals Biodynamics of cholesterol and bile acids in the lithiasic hamster

1991 ◽  
Vol 66 (3) ◽  
pp. 479-492 ◽  
Author(s):  
J. Khallou ◽  
M. Riottot ◽  
M. Parquet ◽  
C. Verneau ◽  
C. Lutton
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Cholesterol Synthesis ◽  
Specific Activity ◽  
Plasma Cholesterol ◽  
Dietary Cholesterol ◽  
Young Male ◽  
Cholesterol Absorption ◽  
Biliary Cholesterol ◽  
Faecal Excretion

By using the isotopic equilibrium method in the young male Syrian hamster, the rates of cholesterol turnover processes, i.e. dietary cholesterol absorption, cholesterol synthesis, cholesterol excretion in the faeces and urine and cholesterol transformation into bile acids, were determined in the hamster receiving a control (C) or a lithogenic diet (L) for 7 weeks. At the end of this period the gall bladder of all animals in group L contained cholesterol gallstones. The coefficient of dietary cholesterol absorption was reduced by 26 %, cholesterol synthesis and cholesterol faecal excretion were twofold higher in group L than in group C. Bile acid content in the small intestine was diminished in group L, but bile acid composition was similar in the two groups. The increase in cholesterogenesis in lithiasic animals essentially took place in the liver. Bile acid biosynthesis did not significantly differ in the two groups, but represented only 35 % of total cholesterol input (dietary absorption + internal secretion) in group L ν. 52% in group C. Thus, in the lithiasic hamster, hepatic synthesis of cholesterol and bile acids are not coupled. The molar percentage of cholesterol in bile was twofold higher in group L than in group C but those of bile acids and of phospholipids were not modified. In the lithiasic hamster the specific activity of biliary cholesterol was similar to that in plasma and liver. Consequently, biliary cholesterol does not derive directly from cholesterol newly synthesized in the liver but from hepatic cholesterol rapidly exchangeable with plasma cholesterol.

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