The cholesterol-lowering effect of guar gum in rats is not accompanied by an interruption of bile acid cycling.

A viscous hydrocolloid (guar gum, GG; 2.5% of the diet) or a steroid sequestrant (cholestyramine; 0.5% of the diet) was included in semipurified diets containing 0.2% cholesterol to compare the cholesterol-lowering effects of each agent in rats. In the present model, GG significantly lowered plasma cholesterol (-25%), especially in the density < 1.040 kg/L fraction, whereas cholestyramine was less potent. Bile acid fecal excretion significantly increased only in rats fed cholestyramine, similar to the cecal bile acid pool; the biliary bile acid secretion was accelerated by GG, but not their fecal excretion, whereas GG effectively enhanced neutral sterol excretion. As a result, the total steroid balance (+13 micromol/d in the control) was shifted toward negative values in rats fed the GG or cholestyramine diets (-27 or -50 micromol/d, respectively). Both agents induced liver 3-hydroxy-3-methylglutaryl-CoA reductase, but cholestyramine was more potent than GG in this respect. The present data suggest that, at a relative low dose in the diet, GG may be more effective than cholestyramine in lowering plasma cholesterol by impairing cholesterol absorption and by accelerating the small intestine/liver cycling of bile acids, which is interestingly, accompanied by reduction of bile acid concentration in the large intestine.

The cholesterol-lowering effect of guar gum is not the result of a simple diversion of bile acids toward fecal excretion.

The effects of partially hydrolyzed, nonviscous, guar gum (PHGG) on cholesterol metabolism and digestive balance have been compared with those of native guar gum (GUAR) in rats adapted to 0.4% cholesterol diets. Both types of guar gum elicited acidic fermentations in the large intestine, but only GUAR effectively lowered plasma cholesterol (P < 0.001), chiefly in the triglyceride-rich lipoprotein fraction. The biliary bile acid excretion was significantly enhanced in rats fed GUAR (P < 0.05), as well as the intestinal and cecal bile acid pool (P < 0.001). In rats fed GUAR and to a lesser extent in those fed PHGG, the fecal excretion of bile acids and neutral sterol was higher than in controls (P < 0.01). The digestive balance (cholesterol intake-steroid excretion) was positive in control rats (+47 mumol/d), whereas it was negative in rats fed GUAR (-20 mumol/d), which could involve a higher rate of endogenous cholesterol synthesis. In rats fed PHGG, the steroid balance remained slightly positive. Liver 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity was very low (22 pmol/min/mg protein), owing to cholesterol supplementation, in control rats or in rats fed PHGG, whereas it was markedly higher (+463%) in rats fed GUAR. In conclusion, even if PHGG does alter some parameters of the enterohepatic cycle of cholesterol and bile acids, its effects are not sufficient to elicit a significant cholesterol-lowering effect. The intestinal (ileal or cecal) reabsorption of bile acids was not reduced, but rather increased, by GUAR; nevertheless the intestinal capacities of reabsorption were overwhelmed by the enlargement of the digestive pool of bile acids. In the present model, induction of HMG-CoA reductase probably takes place in the presence of elevated portal bile acid concentrations.

Fermentable carbohydrates exert a more potent cholesterol-lowering effect than cholestyramine.

The purpose of this work was to assess the respective role of bile acid excretion and of the end-products of cecal fermentations in the cholesterol-lowering effect of complex carbohydrates. The effects of two different fermentable carbohydrates (guar gum, beta-cyclodextrin), and sequestrant resin (cholestyramine) have been investigated in male Wistar rats. Guar gum and beta-cyclodextrin are broken down in the large bowel, with fermentation rich in propionic acid (37% against 26% for control), whereas cholestyramine did not enhance cecal fermentation. beta-Cyclodextrin and guar gum were less potent than cholestyramine to enhance bile acids and sterol excretion. Nevertheless, fermentable carbohydrates exerted a more potent cholesterol-lowering effect than cholestyramine. beta-Cyclodextrin also depressed triacylglycerol-rich lipoprotein (TGRLP). Fermentable carbohydrates lowered cholesterol of LDL and HDL1 fractions. The induction of hepatic HMG-CoA reductase was practically proportional to rate of fecal steroid excretion. Moreover, with beta-cyclodextrin, hepatic HMG-CoA reductase induction was concomitant to a decrease in fatty acid synthase (FAS) activity. Thus, the cholesterol-lowering effect of fermentable carbohydrates could be related to a depressed lipogenesis, as well as to an accelerated removal of HDL1, in relation to an elevated hepatic demand of cholesterol. In conclusion, fermentable carbohydrates could favour cholesterol elimination and have a general lipid-lowering effect by exerting more complex physiological effects than cholestyramine.

Quercetin metabolites in plasma of rats fed diets containing rutin or quercetin.

We studied the bioavailability and the plasma transport of flavonols in rats fed quercetin or rutin diets. Wistar rats were fed one of the following purified diets for 10 d: control; 16.4 or 8.2 mmol rutin/kg diet; or 16.4, 8.2 or 4.1 mmol quercetin/kg diet. Flavonol concentrations were determined in plasma, ileal and cecal contents, and feces. In rats fed diets containing 16.4 mmol quercetin or rutin/kg, the concentration of circulating flavonols was approximately 115 mumol/L. Quercetin or rutin administration resulted in similar concentrations of quercetin in cecal contents. By HPLC analysis and beta-glucuronidase/sulfatase treatment, plasma flavonols have been identified as conjugated quercetin itself, or a conjugated form (4.5-fold as abundant) of an aglycone less polar than quercetin. Rats fed quercetin or rutin diets had a green/yellow-colored plasma that exhibited a peak absorbance at 411 nm, vs. 363 or 375 nm for pure rutin or quercetin solutions, respectively. This shift of band I absorption was obtained when pure quercetin was in the presence of albumin or added to a plasma fraction. The bathochromic properties of flavonoids in the presence of albumin are highly dependent on the presence of the C-2/C-3 double bond on the C-ring and are influenced by the degree of B-ring hydroxylation. The existence of intermolecular bonds between albumin and quercetin is supported by in vitro absorbance and fluorescence studies. With human albumin, the fluorescence intensity and the shift of quercetin absorbance increased in parallel to the albumin/quercetin molar ratio. Conjugated diene formation, resulting from Cu(2+)-catalyzed oxidation of human LDL or rat VLDL+LDL was effectively inhibited in vitro by 0.5 mumol/L quercetin. These results show that dietary flavonols are recovered in rat plasma as conjugated metabolites in non-negligible concentrations, and that these flavonols may be interesting antioxidant micronutrients with a variety of biological effects.

Effect of cyclodextrin on plasma lipids and cholesterol metabolism in the rat.

beta-Cyclodextrin (beta-CD) is a bile acid and sterol sequestrant produced by enzymatic modification of starch; this product has the potential to decrease plasma cholesterol. In contrast to the sequestrants having resin- or saponin-like properties, beta-CD is rapidly broken down by the large intestine microflora. beta-CD effects on cecal fermentations and lipid metabolism were thus investigated in rats adapted to semipurified diets containing 0%, 2.5%, or 5% beta-CD. In rats fed beta-CD diets, there was an enlargement of the cecum together with a dramatic increase in the cecal concentration of propionic acid (even with the 2.5% level, in moderately acidic pH conditions). Propionic acid produced in the cecum was readily absorbed and entirely taken up by the liver, whereas there was no significant acetic acid uptake. Dietary beta-CD was highly effective in enhancing bile acid entry into to the cecum: the cecal bile acids pool was 2.2 and 3.6-fold enlarged in rats fed the 2.5% and 5% beta-CD diets, respectively. The solubility percentage of bile acids decreased to approximately 25% in rats fed the beta-CD diets (v 51% in controls); the cecal concentration of soluble bile acids was thus relatively low in these animals. The fecal excretion of steroids was strongly enhanced by beta-CD, and bile acids excretion was practically proportional to the dietary beta-CD level. There was a net lipid-lowering effect of beta-CD, even at the 2.5% level. The effect was more pronounced on triglycerides than on cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of dietary propionic acid and bile acid excretion in the hypocholesterolemic effects of oligosaccharides in rats.

The aim of this study was to evaluate the influence of dietary propionic acid and bile acid excretion on the hypocholesterolemic effect of fibers. For this purpose, rats were adapted to a diet containing 10 g inulin, 10 g beta-cyclodextrin, or 2.5 g calcium propionate per 100 g diet. Both the inulin and beta-cyclodextrin diets elicited high propionic acid fermentations in the cecum (approximately 45% of total short-chain fatty acids) with relatively low molar proportions of acetic and butyric acids. In rats fed the three experimental diets, 5-7 mumol/min of propionic acid was absorbed in the portal vein, and propionic acid was entirely metabolized by the liver. Plasma cholesterol was more effectively depressed by the beta-cyclodextrin diet than by the inulin diet; the propionic acid-supplemented diet was ineffective in this respect. The inulin diet slightly increased fecal bile acid excretion, compared with the control diet, whereas beta-cyclodextrin markedly enhanced (1.8-fold) bile acid excretion. Microsomal hydroxymethylglutaryl-CoA (HMG-CoA) reductase activity was slightly depressed in rats fed the propionic acid-supplemented diet, whereas it was enhanced by the beta-cyclodextrin diet in parallel to the activity of cholesterol 7 alpha-hydroxylase. The present data suggest that absorption and further hepatic metabolism of large amounts of propionic acid are not sufficient to counteract the induction of HMG-CoA reductase resulting from bile acid fecal losses. The rise of these losses plays a major role in the hypocholesterolemic effect of beta-cyclodextrin.