scholarly journals Effects of dietary polychlorinated biphenyls on cholesterol catabolism in rats

1990 ◽  
Vol 64 (1) ◽  
pp. 161-169 ◽  
Author(s):  
Satoshi Nagaoka ◽  
Hitoshi Miyazaki ◽  
Yoritaka Aoyama ◽  
Akira Yoshida
Keyword(s):  
Polychlorinated Biphenyls ◽  
Bile Acids ◽  
Cholesterol Synthesis ◽  
Control Group ◽  
Hepatic Cholesterol ◽  
Biliary Cholesterol ◽  
Faecal Excretion ◽  
Hepatic Cholesterol Synthesis ◽  
Total Bile Acids

Dietary polychlorinated biphenyls (PCBs) caused hypercholesterolaemia in rats. The concentration and output of biliary cholesterol was significantly lower than that of the control group. Biliary output of total bile acids was significantly decreased in rats given the PCB-supplemented diet. Faecal excretion of total steroids (sum of neutral steroids and acidic steroids) was not significantly changed in rats given the PCB-supplemented diet. The present results indicate that dietary PCBs cause hypercholesterolaemia without modifying the faecal total steroids excretion. These results suggest that PCBs produce hyper-cholesterolaemia accompanied by changes in biliary or faecal excretion of bile acids and neutral steroids in addition to an increase in hepatic cholesterol synthesis.

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.

Relationship between Hepatic Cholesterol Synthesis and Biliary Cholesterol Secretion in Man: Hepatic Cholesterol Synthesis is not a Major Regulator of Biliary Lipid Secretion

1982 ◽  
Vol 62 (5) ◽  
pp. 515-519 ◽  
Author(s):  
P. N. Maton ◽  
A. Reuben ◽  
R. H. Dowling
Keyword(s):  
Bile Acid ◽  
Cholesterol Synthesis ◽  
Acid Output ◽  
Hepatic Cholesterol ◽  
Biliary Cholesterol ◽  
Lipid Secretion ◽  
Hepatic Cholesterol Synthesis ◽  
Biliary Cholesterol Secretion ◽  
Cholesterol Secretion

1. To examine the role of newly synthesized cholesterol as a determinant of bile lipid secretion, both hepatic cholesterol synthesis (as judged by the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, EC 1.1.1.34; HMGCoAR) and steady state biliary cholesterol output were measured in nine patients. 2. HMGCoAR levels varied four fold (9–40 pmol min−1 mg−1) and biliary cholesterol secretion 2–5-fold (0.60−1.15 μUmol h−1 kg−1) but there was no correlation between these two variables (r = 0.18; P>0.05) nor between biliary bile acid output and HMGCoAR activity (r = 0.34; P>0.05). 3. There was, however, a linear relationship between bile acid and phospholipid secretion (r = 0.77; P<0.001) and between bile acid and cholesterol secretion (r = 0.69; P<0.05). 4. These results suggest that HMGCoAR activity is not a major determinant of cholesterol secretion nor at these secretion rates is HMGCoAR activity related to bile acid return to the liver.

Effect of stearic acid and cholesterol on biosynthesis of sterol by the chicken liver

1960 ◽  
Vol 198 (1) ◽  
pp. 29-32 ◽  
Author(s):  
T. M. Lin ◽  
Esko Karvinen ◽  
A. C. Ivy
Keyword(s):  
Stearic Acid ◽  
Cholesterol Synthesis ◽  
Chicken Liver ◽  
Control Group ◽  
Hepatic Cholesterol ◽  
Hepatic Cholesterol Synthesis ◽  
Hepatic Synthesis

The liver of the chicken synthesizes cholesterol from C14-1-acetate. Stearic acid fed to chickens at a 10% level by weight in the diet was associated with a significant increase in the rate of hepatic cholesterol synthesis above that of the control group. Neither our observations nor those in the literature on other species reveal whether the observed augmentation was due to the saturation of the stearic acid. The feeding of cholesterol at a level of 2.5% by weight of the diet decidedly inhibited the hepatic synthesis of cholesterol whether 10% stearic acid was present in (76% inhibition) or absent from the diet (78% inhibition). A relatively large (23%) hepatic synthesis of cholesterol occurred when the diet contained more cholesterol than could be absorbed under the conditions of this experiment.

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.

Increase in serum and bile cholesterol and HMG-CoA reductase by lovastatin in rats

1991 ◽  
Vol 260 (4) ◽  
pp. G625-G630 ◽  
Author(s):  
S. Yamauchi ◽  
W. G. Linscheer ◽  
D. H. Beach
Keyword(s):  
Cholesterol Synthesis ◽  
Reductase Activity ◽  
Blood Cholesterol ◽  
Biliary Lipid ◽  
Hepatic Cholesterol ◽  
Biliary Cholesterol ◽  
Hmg Coa Reductase ◽  
Hepatic Cholesterol Synthesis ◽  
Microsomal Membranes ◽  
Coa Reductase

Lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, is effective in the treatment of hypercholesterolemic patients and is currently being evaluated as a potential agent for dissolving gallstones. We therefore evaluated its effect on cholesterol metabolism in a rat model. A low-cholesterol diet containing 0.1% lovastatin was fed 15 h and 7 and 21 days. Microsomal HMG-CoA reductase activity, hepatic cholesterol synthesis, blood cholesterol, and biliary lipid output were determined and compared with control rats. Hepatic cholesterol synthesis increased ninefold after 7 days and levels of HMG-CoA reductase activity sevenfold. Biliary cholesterol excretion maximally increased fourfold. Biliary lipid output was still elevated after 21 days of treatment (cholesterol 3-fold and phospholipid 2-fold, P less than 0.01). Bile salt output did not change. Augmented responses to lovastatin were present but less on the high-cholesterol diet. The data are consistent with the hypothesis that lovastatin increases HMG-CoA reductase activity through a feedback mechanism that promoted increased cholesterol synthesis, biliary lipid secretion, and elevated blood cholesterol. There was an apparent coupling of biliary cholesterol output with phospholipids but not with bile salts. Although lovastatin also increased microsomal HMG-CoA reductase activity in humans, cholesterol synthesis is not stimulated but is inhibited. This may be explained by higher permeability of the microsomal membranes for lovastatin. Thus the effect of HMG-CoA reductase inhibitors on cholesterol synthesis in different species should then depend on the properties of microsomal membranes.

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