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.

Agents affecting lipid metabolism. XXXI. Properties of an inhibitor of cholesterol synthesis present in rabbit liver mitochondria

1968 ◽  
Vol 46 (2) ◽  
pp. 179-187 ◽  
Author(s):  
M. N. Cayen ◽  
D. Dvornik
Keyword(s):  
Cholesterol Synthesis ◽  
Liver Mitochondria ◽  
Aqueous Extracts ◽  
Hepatic Cholesterol ◽  
Large Molecules ◽  
Hepatic Cholesterol Synthesis ◽  
Significant Enrichment ◽  
Liver Homogenates ◽  
Mitochondrial Extract

Aqueous extracts of mitochondria from livers of starved animals have been reported to inhibit hepatic cholesterol synthesis. Some properties of a mitochondrial extract prepared from starved rabbits have been studied. The extract depressed the incorporation of both 2-14C-acetate and 3H-mevalonate into cholesterol by rat liver homogenates, giving concentration–dependent responses. The active factor was unstable to heat, but stable under in vitro incubation conditions, to pH changes, and to storage in the dark and cold. It was cationic and associated with one or more large molecules (mol. wt. 50 000–150 000); it was not cleaved by trypsin digestion. Fractionation experiments did not result in any significant enrichment of inhibitory activity.

IN VIVO INHIBITION OF CHOLESTEROL BIOSYNTHESIS BY A MITOCHONDRIAL EXTRACT

1961 ◽  
Vol 39 (4) ◽  
pp. 747-755 ◽  
Author(s):  
B. B. Migicovsky
Keyword(s):  
Cholesterol Synthesis ◽  
Cholesterol Biosynthesis ◽  
Liver Mitochondria ◽  
Blood Cholesterol ◽  
Active Principle ◽  
Aqueous Extracts ◽  
Inhibitory Substance ◽  
Cholesterol Levels ◽  
Mitochondrial Extract

Aqueous extracts of liver mitochondria were administered to rats by intraperitoneal, subcutaneous, and oral routes, and C14-acetate or mevalonate was injected intraperitoneally 3 hours later. Cholesterol synthesis in vivo from C14-acetate was depressed by the inhibitory substance in the mitochondrial extracts. Synthesis from C14-mevalonate was not inhibited.Active extracts were prepared from livers of rat, rabbit, pig, and sheep. An inhibitory substance is present in blood serum and administration of active mitochondrial extracts depressed blood cholesterol levels. Pending its identification, the active principle has been provisionally termed I.C.S. (inhibitor of cholesterol synthesis).

Lactoferrin promotes bile acid metabolism and reduces hepatic cholesterol deposition by inhibiting the farnesoid X receptor (FXR)-mediated enterohepatic axis

2019 ◽  
Vol 10 (11) ◽  
pp. 7299-7307 ◽  
Author(s):  
Chen-Jie Ling ◽  
Jia-Ying Xu ◽  
Yun-Hong Li ◽  
Xing Tong ◽  
Huan-Huan Yang ◽  
...  
Keyword(s):  
Body Weight ◽  
Lipid Metabolism ◽  
Bile Acid ◽  
Acid Metabolism ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Hepatic Cholesterol ◽  
Reduce Body Weight ◽  
Regulate Lipid Metabolism

Lactoferrin (LF) is a multifunctional glycoprotein that can regulate lipid metabolism, lower cholesterol, reduce body weight, and prevent atherosclerosis.

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.

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.

Agents affecting lipid metabolism. XXXIX. Effect of combined administration of ethyl chlorophenoxyisobutyrate and cholestyramine on cholesterol biosynthesis in the rat

1970 ◽  
Vol 48 (9) ◽  
pp. 1022-1023 ◽  
Author(s):  
M. N. Cayen ◽  
D. Dvornik
Keyword(s):  
Lipid Metabolism ◽  
Cholesterol Synthesis ◽  
Cholesterol Biosynthesis ◽  
Combined Effect ◽  
Hepatic Cholesterol ◽  
Hepatic Cholesterol Synthesis ◽  
Combined Administration ◽  
Liver Homogenates

Rats were fed ethyl p-chlorophenoxyisobutyrate (CPIB) and cholestyramine, alone and in combination. Regarding levels of circulating cholesterol, cholestyramine had no effect, while a fall was observed with CPIB given alone or in combination with cholestyramine. Subsequently, the combined effect of both agents was elicited by measuring the incorporation of 2-14C-acetate into cholesterol by liver homogenates of treated rats; addition of CPIB decreased the cholestyramine-induced increase in the rate of hepatic cholesterol synthesis.

Effects of 3,5,3' -D-triiodothyronine on lipid metabolism in hypothyroidism

1962 ◽  
Vol 203 (3) ◽  
pp. 513-516 ◽  
Author(s):  
Joseph M. Merrill ◽  
Janet Lemley-Stone
Keyword(s):  
Fatty Acids ◽  
Oxygen Consumption ◽  
Lipid Metabolism ◽  
Cholesterol Synthesis ◽  
Thyroid Tissue ◽  
Liver Cholesterol ◽  
Radioactive Carbon ◽  
Fatty Acid Utilization ◽  
Weanling Rats ◽  
Total Body

To study the effects of 3,5,3'-d-triiodothyronine (d-T3) on oxygen consumption and lipid metabolism, thyroid deficiency was produced by administration of I131 to weanling rats. Hypothyroidism was evidenced by decreased growth and O2 consumption, with absence of functioning thyroid tissue at necropsy. Administration of d-T3 produced a transient fall in serum cholesterol and a more protracted fall in serum fatty acids. This was associated with a decrease in liver fatty acids and an increase in liver cholesterol. Simultaneously, incorporation of radioactive carbon into liver fatty acids and cholesterol of d-T3-treated animals was greatly increased. Total-body O2 consumption and Qo2 of myocardial homogenates were increased in animals treated with d-T3. From these data it is suggested that the hypolipemic and calorigenic effects of d-T3 are interdependent and administration at this dose level increases fatty acid utilization and cholesterol synthesis by the liver.

FURTHER STUDIES WITH THE MITOCHONDRIAL INHIBITOR OF CHOLESTEROL SYNTHESIS

1964 ◽  
Vol 42 (1) ◽  
pp. 105-110 ◽  
Author(s):  
B. B. Migicovsky
Keyword(s):  
Aqueous Extract ◽  
Inhibitory Activity ◽  
Protein Fraction ◽  
Cholesterol Synthesis ◽  
Liver Homogenate ◽  
Liver Mitochondria ◽  
Active Principle ◽  
Mitochondrial Extract ◽  
Mitochondrial Inhibitor

The inhibitory activity of an aqueous extract of liver mitochondria (I.C.S.) was observed with Triton-treated rats. Fractionation of I.C.S. on Sephadex indicated that the active principle comes off the Sephadex with the protein fraction. Inhibitory activity was shown to be present in the 100,000 × g supernate of the liver homogenate of a starved rat, indicating that the active principle moves from the mitochondrion to the surrounding cytoplasm.Electrodialysis of the mitochondrial extract revealed that the inhibitor is permeable and moves to the cathode. The electrodialyzed material was found to be active as an inhibitor of cholesterol synthesis in vitro and in vivo.It is concluded that the active principle is associated with protein and may be separated therefrom by electrodialysis.

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.

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