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- Reihner, E, et al.
(författare)
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Lithogenic diet and gallstone formation in mice: integrated response of activities of regulatory enzymes in hepatic cholesterol metabolism
- 1996
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Ingår i: The British journal of nutrition. - : Cambridge University Press (CUP). - 0007-1145 .- 1475-2662. ; 76:5, s. 765-772
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Tidskriftsartikel (refereegranskat)abstract
- Supersaturation of bile with cholesterol is a prerequisite of the development of gallstones. With the intention to study the integrated response of enzymes regulating hepatic cholesterol metabolism during gallstone formation we used an established model for the induction of cholesterol gallstone disease in mice. Ten mice were fed on a lithogenic diet containing 10 g cholesterol/kg and 5 g cholic acid/kg for 8 weeks and were compared with ten mice fed on a standard pellet diet. Cholesterol crystals or gallstones developed in 90% of gallbladders in treated mice. The lithogenic diet had an inhibitory effect on the rate-limiting enzyme of cholesterol biosynthesis, hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase (EC1.1.1.88) activity, 39·6 (SEM 2·8)v. 171·0 (SEM 47·3) pmol/min per mg protein. Cholesterol 7α-hydroxylase (EC1.14.13.17) activity, regulating bile acid synthesis, was decreased by 80%, and this was assumed to be due to cholic acid in the diet. The cholesterol-enriched diet also induced a tenfold increase in cholesterol esterification rate in the liver, i.e. acyl-CoA: cholesterol acyl transferase (ACAT;EC2.3.1.26) activity. The total, as well as esterified, cholesterol contents of liver homogenates were significantly higher in cholesterol- and cholic acid-treated mice and correlated well with the ACAT activity (rs0·72 (P < 0·005), and rs0·68 (P < 0·01) respectively). A significantly higher ACAT activity was obtained in mice given cholesterol and cholic acid even when the enzyme was saturated with exogenous cholesterol, thus indicating an increased amount of the enzyme. The formation of gallstones is dependent on a delicate balance between lithogenic factors (increased absorption of cholesterol and reduced secretion of bile acids) and defence mechanisms (decreased synthesis and increased esterification of cholesterol). In the specific animal model studied here the two defence mechanisms cannot compensate for the increased absorption of cholesterol and the reduced synthesis of bile acids.
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| 2. |
- Berggren, A M, et al.
(författare)
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Influence of orally and rectally administered propionate on cholesterol and glucose metabolism in obese rats
- 1996
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Ingår i: British Journal of Nutrition. - 0007-1145. ; 76:2, s. 94-287
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Tidskriftsartikel (refereegranskat)abstract
- It has increasingly been suggested that the short-chain fatty acids (SCFA) acetic, propionic and butyric acids, derived from colonic fermentation of dietary fibre and other indigestible carbohydrates, exert different physiological effects. Formation of propionic acid is discussed in terms of beneficial effects on glucose and cholesterol metabolism. The aim of the present study was to evaluate possible metabolic effects of propionic acid and to differentiate between effects mediated in the upper gastrointestinal tract and those mediated in the hind-gut. For this purpose, obese hyperinsulinaemic (fa/fa) rats were studied during a 19 d test period. Sodium propionate was either fed orally through the diet (1 g/d), or infused rectally (0.15 g/d) to animals given diets high in cholesterol (20 g/kg) and saturated fat (130 g/kg). At the end of the test period total liver cholesterol pools were 20% lower (P < 0.01) in rats given dietary or rectally infused propionate (481 and 484 mg respectively) compared with the control group (614 mg). This was due to lower liver weights (P < 0.05) in propionate-treated animals, 15.5 and 15.3 g, v. 18.2 g in the control group, and no differences were noted in hepatic cholesterol concentrations. The urinary glucose excretion was measured during days 15-19 and was found to be lower (P < 0.05) in rats fed with propionate (23 mg) compared with the control group or the group infused rectally (39 and 38 mg respectively). In addition, fasting plasma glucose concentrations decreased significantly (P < 0.05) over the test period. It is concluded that orally supplied propionate affects both glucose and cholesterol metabolism as judged from lowered urinary glucose excretion, fasting blood glucose and liver cholesterol pools. On the other hand, propionate administered to the hind-gut at a physiologically relevant level reduces the hepatic cholesterol pool.
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| 5. |
- Livesey, G, et al.
(författare)
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Determination of digestible energy values and fermentabilities of dietary fibre supplements : a European interlaboratory study in vivo
- 1995
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Ingår i: British Journal of Nutrition. - 0007-1145. ; 74:3, s. 289-302
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Tidskriftsartikel (refereegranskat)abstract
- The performance of methods to determine energy conversion factors for dietary fibre (DF) supplements and fermentability (D) values of their non-starch polysaccharides (NSP) was investigated. Heats of combustion, digestible energy (DE) and D values were determined on five DF supplements in five European laboratories on five separate occasions. In each instance the DF supplements were fed to juvenile male Wistar rats at two doses, 50 and 100 g/kg basal diet, for 3 weeks with food and faeces collected in the 3rd week. Among-laboratory variations in heats of combustion (delta Hc) were < 2%. DE values (kJ/g dry weight) at the upper and lower doses respectively were: 10.4 and 9.9 for a high-methoxyl apple pectin, 9.5 and 9.4 for a sugar-beet DF supplement, 12.2 and 12.7 for soyabean DF supplement, 3.8 and 4.0 for maize bran, and 0.3 and 0.3 for Solka-floc cellulose. Variations among laboratories, among occasions and among animals were < 1, < 2 and < 2.5 kJ/g respectively. The among-occasion: among-laboratory variance ratio for DE was 0.5, suggesting the method performed equally well in all laboratories. There was no evidence of learning of fatigue or fatigue in the performance of the method. D values were also independent of dose and at the high and lower doses were: pectin 0.92 and 0.95, sugar-beet NSP 0.68 and 0.68, soyabean NSP 0.86 and 0.88, maize bran 0.17 and 0.18, cellulose 0.07 and 0.06. Among-laboratory variance tended to increase with decreasing fermentability and ranged from 0.03 to 0.18. The DE and D data were not significantly different from a previously proposed relationship DE = 0.7 x delta Hc x D, where delta Hc is the heat of combustion of the supplement. We conclude that while the among-laboratory variation in the D of difficult-to-ferment NSP is too large for the reliable prediction of energy value the method for the direction determination of DE is both reproducible and repeatable, that DE is independent of dosage of DF supplement up to 100 g/kg diet, and that it is safe to discriminate between energy values with a precision of 3 kJ/g. The conversion of both DE and D to net metabolizable energy for the purpose of food labelling, tables and databases is described.
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