Influence of Bile Acids on the Activity of Rat Liver 3‐Hydroxy‐3‐methylglutaryl Coenzyme A Reductase

Hamprecht, Bernd; Roscher, Rudolph; Waltinger, Gudrun; Nüssler, Christa

doi:10.1111/j.1432-1033.1971.tb01208.x

Cited by 60 publications

(12 citation statements)

References 16 publications

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“…* Values that differ from the control values (group B) at the P c 0.05 level. (24). To obtain more definitive data in this critical group of animals, 24 more rats were prepared with intestinal lymphatic cannulae, and half of these were infused with taurocholate.…”

Section: Methodsmentioning

confidence: 99%

“…In earlier work we found no evidence that bile acids have a direct regulatory effect upon the rate-limiting enzyme, 8-hydroxy-,B-methylglutaryl-CoA reductase (HMG CoA reductase),' in the cholesterol bio-synthetic pathway and suggested that the principal effect of bile acid was to modulate the amount of cholesterol absorbed from the gastrointestinal tract (23). Subsequent work, however, has demonstrated that cholesterol synthesis in the liver is suppressed by bile acid feeding under circumstances where cholesterol absorption is partially, or perhaps completely, blocked by the administration of 8-sitosterol (20) or by intestinal lymphatic diversion (24). Alternatively, hepatic cholesterol synthesis has been found to be enhanced after resection of the terminal ileum under circumstances where cholesterol absorption apparently is unchanged (25).…”

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confidence: 99%

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The mechanisms of and the interrelationship between bile acid and chylomicron-mediated regulation of hepatic cholesterol synthesis in the liver of the rat.

Nervi¹

1978

J. Clin. Invest.

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A B S T R A C T Hepatic cholesterol synthesis is controlled both by the size of the bile acid pool in the enterohepatic circulation and by the amount of cholesterol reaching the liver carried in chylomicron remnants. These studies were undertaken to examine how these two control mechanisms are interrelated. When the size of the pool was systematically varied, the logarithm of the rate of hepatic cholesterol synthesis varied in an inverse linear fashion with the size of the taurocholate pool between the limits of 0 and 60 mg of bile acid per 100 g of body weight. The slope of this relationship gave the fractional inhibition of cholesterol synthesis associated with expansion of the taurocholate pool and was critically dependent upon the amount of cholesterol available for absorption from the gastrointestinal tract. Furthermore, the degree of inhibition of cholesterol synthesis in the liver seen with taurocholate feeding was reduced by partially blocking cholesterol absorption with ,3-sitosterol even though the bile acid pool was still markedly expanded. In rats with diversion of the intestinal lymph from the blood, a fivefold expansion of the taurocholate pool resulted in only slight suppression of the rate of hepatic cholesterol synthesis, and even this inhibition was shown to be attributable to small amounts of cholesterol absorbed through collateral lymphatic vessels and (or) to a fasting effect. Similarly, the infusion of either taurocholate or a combination of taurocholate and taurochenate into rats with no biliary or dietary cholesterol available for absorption caused no suppression of hepatic cholesterol synthesis. Finally, the effect of changes in the rate of bile acid synthesis on hepatic cholesterol synthesis

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

The mechanisms of and the interrelationship between bile acid and chylomicron-mediated regulation of hepatic cholesterol synthesis in the liver of the rat.

Nervi¹

1978

J. Clin. Invest.

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“…Hamprecht et al (28) diverted the lymph and hence any absorption of cholesterol, and fed bile salts to these rats. They found that cholic acid feeding under these circumstances was effective in reducing the level of hepatic H1MG CoA reductase.…”

Section: A D Coopermentioning

confidence: 99%

The regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the isolated perfused rat liver.

Cooper¹

1976

J. Clin. Invest.

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A B S T R A C T The effect of perfusion of an isolated rat liver on hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase was studied. In liver removed during the basal period of the diurnal cycle of enzyme activity, a 227±41% increase in enzyme activity occurred after 3 h of a l)lasna-free perfusion. This could be prevented by the addition of cycloheximide or pure cholesterol (dispersed with lecithin) to the perfusate. In contrast, the continuous addition of taurocholate or taurochenodeoxycholate, alone or in combination, at a variety of rates did not prevent the increase in enzyme activity. The added bile salts were efficiently extracted from the perfusate and excreted in the bile. The addition of these bile salts to a cholesterol-enriched perfusate did not alter the effect obtained with cholesterol alone.If the perfusate contained whole serum, the increase induced by perfusion in the basal period was smaller (88±27%) than with plasma-free perfusate. Again, the major bile salts of the rat failed to prevent the increase in enzyme activity induced by liver perfusion.If livers were removed and perfused at the height of the diurnal cycle of enzyme activity, the enzyme activity remained high (2+10% increase) rather than decreasing, as occurs in vivo. If cholesterol was added to these perfusions, a 52-+-4% decrease was induced. Bile salt addition induced no decrease. From these results it is concluded that the major bile salts are not direct regulators of hepatic cholesterol synthesis, but pure cholesterol, in the absence of bile salt or lipoprotein, is able to initiate the mechanism that represses hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase.

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“…Possibly other stimuli affecting liver 3-hydroxy-3-methylglutaryl-CoA reductase, such as starvation (Linn, 1967;Hamprecht et al, 1969), dietary bile acids (Hamprecht et al, 1971) and other dietary components (Craigetal., 1972), do so non-specifically. At any rate, a test, such as that described in the …”

Section: Resultsmentioning

confidence: 99%

Specificity of the effect of dietary cholesterol on rat liver microsomal 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity (Short Communication)

Gregory

Booth

1975

Biochemical Journal

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Influence of Bile Acids on the Activity of Rat Liver 3‐Hydroxy‐3‐methylglutaryl Coenzyme A Reductase

Cited by 60 publications

References 16 publications

The mechanisms of and the interrelationship between bile acid and chylomicron-mediated regulation of hepatic cholesterol synthesis in the liver of the rat.

The mechanisms of and the interrelationship between bile acid and chylomicron-mediated regulation of hepatic cholesterol synthesis in the liver of the rat.

The regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the isolated perfused rat liver.

Specificity of the effect of dietary cholesterol on rat liver microsomal 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity (Short Communication)

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