Effect of portacaval anastomosis on hepatic HMG‐CoA‐reductase activity in normal rats

Bützow, G H; Ossenberg, F. W.; Becker, Katja; Schudt, Chr.; Gaertner, U

doi:10.1016/0014-5793(77)80062-8

Cited by 6 publications

(6 citation statements)

References 17 publications

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“…These results are consistent with the sterol balance data indicating no difference in hepatic or whole-body cholesterol synthesis. However, our results are not inconsistent with the reports of other investigators that portacaval shunt lowers cholesterol synthesis in man and some experimental animals (8, 13,18,21). As shown in Table 111, less than 20% of the total cholesterol turnover of the animals of this study was due to endogenous cholesterol synthesis.…”

contrasting

confidence: 66%

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Portacaval Shunt and Whole-Body Cholesterol Metabolism in the Cholesterol-Fed African Green Monkey

Parks

Lehner

Clair

et al. 1979

Experimental Biology and Medicine

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contrasting

confidence: 66%

“…This is best exemplified by the studies done with rats in which portacaval shunt has been shown to increase (12), decrease (12)(13)(14)(15), or have no effect (16,17) on serum cholesterol concentrations. Studies with dogs and swine, how-…”

mentioning

confidence: 95%

Portacaval Shunt and Whole-Body Cholesterol Metabolism in the Cholesterol-Fed African Green Monkey

Parks

Lehner

Clair

et al. 1979

Experimental Biology and Medicine

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“…Decreased hepatic cholesterol synthesis has been reported to occur in dogs (3), pigs (4), and rats (5) after PCA. In contrast, studies in baboons (6), dogs (7), and rats (8,9) have shown hepatic cholesterol synthesis to be unchanged or possibly even increased after portal diversion.…”

mentioning

confidence: 99%

“…Normal body growth is essential to the proper interpretation of sterol balance data and of enzyme activities, a prerequisite that has not been met in most of the studies thus far reported (8,14,15 (5,8,9). This weight loss has also been observed in dogs, swine, monkeys, and baboons (26).…”

mentioning

confidence: 99%

Cholesterol homeostasis in the rat with a portacaval anastomosis.

Proia¹,

McNamara²,

Edwards³

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

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Studies were undertaken to determine the effect of portacaval anastomosis on cholesterol homeostasis in rats fed sucrose/lard under conditions of normal body growth. Four to 6 weeks after portacaval shunt surgery, we found decreases in plasma cholesterol and triglyceride concentrations, total liver weight, and hepatic microsomal protein concentration. Measurements of hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (EC 1.1.1.34) activity showed decreases in specific activity and total liver activity in portacaval shunt rats, but the enzyme diurnal rhythm remained. Decreased reductase activity in shunted rats was not due to an altered Km for D-HMG-CoA, nor was an enzyme inhibitor found in the livers of the portacaval shunt animals. Sterol balance measurements in rats with shunts showed a 22% decrease in whole body cholesterol synthesis rate compared to controls. These metabolic studies, coupled with postmortem data, showed diminished bile acid synthesis, unchanged fecal neutral steroid excretion, and decreased net tissue accumulation of cholesterol during growth. The decreased whole body cholesterol synthesis rate ultimately led to a diminished total carcass cholesterol concentration in the rats with shunts.The surgical procedure of portacaval anastomosis (PCA) has provided an effective therapeutic approach in homozygous familial hypercholesteremia in man, as judged by a decrease in plasma cholesterol level and clinical amelioration in the signs and symptoms of premature coronary artery disease. Since the original report in 1973 by Starzl and coworkers (1), more than 30 other patients with this lethal inborn error of metabolism have been subjected to PCA (2); medical procedures (diets or drugs) have usually been ineffective in controlling the rapid progression of atherosclerotic heart disease in this condition. In an attempt to resolve some of these uncertainties, we undertook studies of whole body cholesterol synthesis rates and hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (mevalonate:NADP oxidoreductase, EC 1.1.1.34) activity in PCA rats fed a purified high-carbohydrate diet that allows normal body growth to occur after institution of a PCA (11-13). Normal body growth is essential to the proper interpretation of sterol balance data and of enzyme activities, a prerequisite that has not been met in most of the studies thus far reported (8,14,15 t To whom reprint requests should be addressed.

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“…The mechanism of the cholesterol lowering effect has not been elucidated. In rats the same action ofportacaval anastomosis has been shown provided that a cholesterol free diet is maintained [3]. Thus, the rat with portacaval shunt seems t o be a suitable model for studying the underlying biochemical processes.…”

Section: Introductionmentioning

confidence: 85%

Effect of portacaval shunt on biliary cholesterol and bile salt secretion in normal rats

Bützow¹,

Dammann²,

Czok

1978

Eur J Clin Investigation

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In order to assess the role of bile secretion in the serum cholestrol lowering effect of a portacaval anastomosis in rats, bile flow rate, bile salt and cholesterol secretion in bile were determined. The study comprised five groups of animals: (1) rats with protacaval shunt cholesterol free food ad libitum. (2) sham-operated and pair-fed controls; (3) unoperated, pair-fed controls; (4) unoperated controls on cholesterol free diet ad libitum; and (5) unoperated controls on normal laboratory rat chow ad libitum. Bile flow rate showed no difference in any of the groups on cholesterol free diet. Bile salt secretion was significantly elevated in shunted animals (87.1 +/- 7.0 nmol/min) as compared with pair-fed sham-operated (64.7 +/- 20.0 nmol/min) and unoperated controls (56.0 +/- 22.3 nmol/min). Biliary cholesterol output tended to be higher in shunted animals but this was not statistically significant. The data indicate that the atrophied rat liver in shunted animals is able to maintain a normal bile flow and to increase bile salt secretion. Thus, the serum cholesterol lowering action of a portocaval anastomosis may be partly due to an increased cholesterol catabolism to bile salts.

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Effect of portacaval anastomosis on hepatic HMG‐CoA‐reductase activity in normal rats

Cited by 6 publications

References 17 publications

Portacaval Shunt and Whole-Body Cholesterol Metabolism in the Cholesterol-Fed African Green Monkey

Portacaval Shunt and Whole-Body Cholesterol Metabolism in the Cholesterol-Fed African Green Monkey

Cholesterol homeostasis in the rat with a portacaval anastomosis.

Effect of portacaval shunt on biliary cholesterol and bile salt secretion in normal rats

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