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.

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 The Interpretation of Cholesterol Balance Derived Synthesis Data and Surrogate Noncholesterol Plasma Markers for Cholesterol Synthesis under Lipid Lowering Therapies

Cholesterol ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Frans Stellaard ◽  
Dieter Lütjohann
Keyword(s):  
Cholesterol Synthesis ◽  
De Novo ◽  
Cholesterol Metabolism ◽  
Plasma Cholesterol ◽  
Cholesterol Concentration ◽  
Lipid Lowering ◽  
Fecal Excretion ◽  
Liver Cholesterol ◽  
Hepatic Cholesterol ◽  
Ezetimibe Treatment

The cholesterol balance procedure allows the calculation of cholesterol synthesis based on the assumption that loss of endogenous cholesterol via fecal excretion and bile acid synthesis is compensated by de novo synthesis. Under ezetimibe therapy hepatic cholesterol is diminished which can be compensated by hepatic de novo synthesis and hepatic extraction of plasma cholesterol. The plasma lathosterol concentration corrected for total cholesterol concentration (R_Lath) as a marker of de novo cholesterol synthesis is increased during ezetimibe treatment but unchanged under treatment with ezetimibe and simvastatin. Cholesterol balance derived synthesis data increase during both therapies. We hypothesize the following. (1) The cholesterol balance data must be applied to the hepatobiliary cholesterol pool. (2) The calculated cholesterol synthesis value is the sum of hepatic de novo synthesis and the net plasma—liver cholesterol exchange rate. (3) The reduced rate of biliary cholesterol absorption is the major trigger for the regulation of hepatic cholesterol metabolism under ezetimibe treatment. Supportive experimental and literature data are presented that describe changes of cholesterol fluxes under ezetimibe, statin, and combined treatments in omnivores and vegans, link plasma R_Lath to liver function, and define hepatic de novo synthesis as target for regulation of synthesis. An ezetimibe dependent direct hepatic drug effect cannot be excluded.

Effect of sterol biosynthesis inhibitor, SSF-109, on cholesterol synthesis in isolated rat hepatocytes

Steroids ◽  
1993 ◽  
Vol 58 (2) ◽  
pp. 74-78 ◽  
Author(s):  
Shujiro Seo ◽  
Kanya Tonda ◽  
Atsuko Uomori ◽  
Ken'ichi Takeda ◽  
Masaharu Hirata
Keyword(s):  
Cholesterol Synthesis ◽  
Rat Hepatocytes ◽  
Sterol Biosynthesis ◽  
Isolated Rat Hepatocytes ◽  
Biosynthesis Inhibitor ◽  
Sterol Biosynthesis Inhibitor ◽  
Isolated Rat

scholarly journals Impaired cholesterol metabolism in the mice model of cystic fibrosis. A vicious circle?

2019 ◽  
Author(s):  
Felice Amato ◽  
Alice Castaldo ◽  
Giuseppe Castaldo ◽  
Gustavo Cernera ◽  
Gaetano Corso ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Cholesterol Metabolism ◽  
Cholesterol Biosynthesis ◽  
Cholesterol Absorption ◽  
Vicious Circle ◽  
Liver Cholesterol ◽  
Mice Model ◽  
Hepatic Expression ◽  
Expression Of Genes ◽  
Low Cholesterol

AbstractPatients with cystic fibrosis (CF) have low cholesterol absorption and, despite enhanced endogenous biosynthesis, low serum cholesterol. Herein, we investigated cholesterol metabolism in a murine CF model in comparison to wild type (WT) testing serum and liver surrogate biomarkers together with the hepatic expression of genes involved in cholesterol metabolism. CF mice display lower sterols absorption and increased endogenous biosynthesis. Subsequently, we evaluated the effects of a cholesterol-supplemented diet on cholesterol metabolism in CF and WT mice. The supplementation in WT mice determines biochemical changes similar to humans. Instead, CF mice with supplementation did not show significant changes, except for serum phytosterols (−50%), liver cholesterol (+35%) and TNFα mRNA expression, that resulted 5-fold higher than in CF without supplementation. However, liver cholesterol in CF mice with supplementation resulted significantly lower compared to WT supplemented mice. This study shows that in CF mice there is a vicious circle in which the altered bile salts synthesis/secretion contribute to reduce cholesterol digestion/absorption. The consequence is the enhanced liver cholesterol biosynthesis that accumulates in the cell triggering inflammation.

Effect of diabetes on cholesterol and fatty acid synthesis in the rat aorta

1960 ◽  
Vol 198 (1) ◽  
pp. 25-28 ◽  
Author(s):  
Daniel W. Foster ◽  
Marvin D. Siperstein
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
Cholesterol Synthesis ◽  
Acid Synthesis ◽  
Rat Aorta ◽  
Diabetic Rats ◽  
Liver Cholesterol ◽  
Hepatic Cholesterol ◽  
Hepatic Cholesterol Synthesis ◽  
Normal Controls

The synthesis of cholesterol and fatty acids from acetate-1-C14 was studied in the aortas and livers of 42 diabetic rats and their normal controls. Hepatic cholesterol synthesis was significantly increased in 13, decreased in 13, and unchanged in 16 of the 42 animals. Fatty acid synthesis was depressed in the liver in 39 of the 42 diabetic rats. Aortic cholesterogenesis was increased in only 2 of the 13 aortas from the same rats showing elevated hepatic cholesterol synthesis. Fatty acid synthesis was depressed in 21 of 42 aortas from the diabetic group. It is concluded, therefore, that the aorta is relatively resistant to stimulation of cholesterol synthesis by diabetes even when hepatic cholesterol synthesis in the same animal is elevated. Lipogenesis on the other hand is commonly depressed in the aorta as well as the liver. Cholesterol was purified through dibrominization and both normal and diabetic aortas were shown to be capable of carrying cholesterol synthesis to completion.

Cholesterol metabolism in regenerating liver of the rat

1985 ◽  
Vol 249 (6) ◽  
pp. G679-G684 ◽  
Author(s):  
F. J. Field ◽  
S. N. Mathur ◽  
D. R. LaBrecque
Keyword(s):  
Dna Synthesis ◽  
Partial Hepatectomy ◽  
Rat Liver ◽  
Cholesterol Synthesis ◽  
Cholesterol Metabolism ◽  
Reductase Activity ◽  
Plasma Cholesterol ◽  
Regenerating Liver ◽  
Acyltransferase Activity ◽  
Regenerating Rat Liver

The regenerating rat liver was used as a model to investigate the necessity for new cholesterol synthesis prior to the onset of cell division. Plasma cholesterol levels in partially hepatectomized rats were significantly decreased 24 and 48 h after surgery compared with levels in sham-operated animals. Hepatic cholesteryl ester content was also significantly increased in livers from partially hepatectomized animals, but the hepatic content of unesterified cholesterol was not affected. Hepatic triglyceride content was significantly increased within 6 h after surgery in the regenerating liver. The triglyceride levels reached a peak at 24 h, and by 72 h they had decreased back to levels that were no different from control. In the regenerating liver, microsomal 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase activity was increased 12 h after surgery. The activity of this enzyme remained significantly elevated throughout the 72-h period after surgery. In contrast, 12 h after partial hepatectomy the rate of hepatic cholesterol synthesis was significantly lower than that observed in livers from sham-operated rats. An increase in the rate of cholesterol synthesis was not observed until 48 h after partial hepatectomy, some 32 h after the start of DNA synthesis. Microsomal acyl-CoA:cholesterol acyltransferase activity was unchanged except for a 28% decrease at 72 h after partial hepatectomy. The data suggest that new cholesterol synthesis is not a requirement prior to the initiation of DNA synthesis in the regenerating rat liver.(ABSTRACT TRUNCATED AT 250 WORDS)

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