Cholesterol-lowering effects of guar gum: changes in bile acid pools and intestinal reabsorption.

Soluble fibers such as guar gum (GG) may exert cholesterol-lowering effects. It is generally accepted that bile acid (BA) reabsorption in portal blood is reduced, thus limiting the capacity of BA to down-regulate liver cholesterol 7alpha-hydroxylase, the rate-limiting enzyme of BA synthesis. In the present work, rats were adapted to fiber-free (FF) or 5% GG diets (supplemented or not with 0.25% cholesterol), to investigate various aspects of enterohepatic BA cycling. GG in the diet at a level of 5% elicited a significant lowering of plasma cholesterol during the absorptive period, in cholesterol-free (-13%) or 0.25% cholesterol (-20%) diet conditions. In rats adapted to the GG diets, the small intestinal and cecal BA pools and the ileal vein-artery difference for BA were markedly enhanced; reabsorption in the cecal vein was also enhanced in these rats. [14C]Taurocholate absorption, determined in perfused ileal segments, was not significantly different in rats adapted to the FF or GG diet, suggesting that a greater flux of BA in the ileum might support a greater ileal BA reabsorption in rats adapted to the GG diet. In contrast, capacities for [14C]cholate absorption from the cecum at pH 6.5 were higher in rats adapted to the GG diet than to the FF diet. Acidification of the bulk medium in isolated cecum (from pH 7.1 down to pH 6.5 or 5.8) or addition of 100 mM volatile fatty acids was also found to stimulate cecal [14C]cholate absorption. These factors could contribute to accelerated cecal BA absorption in rats fed the GG diet. The effects of GG on steroid fecal excretion thus appear to accompany a greater intestinal BA absorption and portal flux to the liver. These results suggest that some mechanisms invoked to explain cholesterol-lowering effect of fibers should be reconsidered.

Effects of soluble corn bran arabinoxylans on cecal digestion, lipid metabolism, and mineral balance (Ca, Mg) in rats.

The effects of soluble corn bran arabinoxylans on cecal digestion, lipid metabolism, and mineral utilization [calcium (Ca) and magnesium (Mg)] were investigated in rats adapted to semipurified diets. The diets provided either 710 g/kg wheat starch alone (control) or 610 g/kg wheat starch plus 100 g/kg corn soluble fiber (arabinoxylans) and either 0 or 2 g/kg cholesterol (control + cholesterol and arabinoxylans + cholesterol, respectively). Compared with rats fed the control diets, rats fed the arabinoxylan diets had significant cecal hypertrophy (+50% after 3 days of the fiber adaptation) and an accumulation of short-chain fatty acids, especially propionic acid (up to 45% in molar percentage). Arabinoxylans enhanced the cecal absorption of Ca and Mg (from 0.07 to 0.19 micromol/min for Ca and from 0.05 to 0.23 micromol/min for Mg). Mg balance was enhanced by arabinoxylans (+25%). The arabinoxylan diet markedly reduced the cholesterol absorption from 50% of ingested cholesterol in controls up to approximately 15% in rats adapted to the arabinoxylans diet. Arabinoxylans were effective in lowering plasma cholesterol (approximately -20%). There was practically no effect of the diets on cholesterol in d > 1.040 lipoproteins (high density lipoproteins) whereas arabinoxylans were very effective in depressing cholesterol in d < 1.040 lipoproteins (especially in triglyceride-rich lipoproteins). Corn fermentable fiber decreased the accumulation of cholesterol in the liver. In parallel, the arabinoxylan diet counteracted the downregulation of 3-hydroxy-3-methylglutaryl-CoA by cholesterol. These data suggest that arabinoxylans may have a great impact on intestinal fermentation, mineral utilization, and cholesterol metabolism.

Effectiveness of resistant starch, compared to guar gum, in depressing plasma cholesterol and enhancing fecal steroid excretion.

Amylase-resistant starch (RS) represents a substrate that can be administered in substantial amounts in the diet, in contrast to gel-forming polysaccharides, such as guar gum (GG). The aim of this work was thus to compare the effects of GG and RS on cholesterol metabolism in rats adapted to 0.4% cholesterol diets, using dietary GG or RS levels (8 or 20%, respectively) that led to a similar development of fermentations, as assessed by the degree of enlargement of the cecum. The RS diet elicited a marked rise in the cecal pool of short-chain fatty acids, especially acetic and butyric acid, whereas the GG diet favored high-propionic acid fermentations. Both polysaccharides markedly altered the cholesterol excretion, from 50% of ingested cholesterol in controls, up to about 70% in rats adapted to the RS or GG diets. With these diets, the fecal excretion of bile acids was enhanced (67 and 144% with the RS and GG diets, respectively). RS and GG diets were effective in lowering plasma cholesterol (about -40%) and triglycerides (-36%). There was practically no effect of the diets on cholesterol in d > 1.040 lipoproteins (high density lipoproteins), whereas RS (and to a larger extent, GG) were very effective to depress cholesterol in d < 1.040 lipoproteins (especially in triglyceride-rich lipoproteins). Fermentable polysaccharides counteracted the accumulation of cholesterol in the liver, especially cholesterol esters. In parallel, liver acyl CoA:cholesterol acyltransferase was depressed in rats fed the RS or GG diets, whereas only the GG diet counteracted the downregulation of 3-hydroxy-3-methylglutaryl-CoA by cholesterol. These data suggest that RS may be practically as effective as a gel-forming gum, such as GG, on steroid excretion and on cholesterol metabolism.

Methionine deficiency in rats fed soy protein induces hypercholesterolemia and potentiates lipoprotein susceptibility to peroxidation.

A number of studies have provided evidence that plant proteins, especially soy protein, have a cholesterol-lowering effect as compared with casein. However, dietary supply of sulfur amino acids may be deficient when soy protein is present in the diet at a suboptimal level, which could affect lipid metabolism. Accordingly, in rats fed 13% protein diets, soy protein feeding resulted in a cholesterol-increasing effect (+18%), which could be counteracted by methionine supplementation (0.4%). In contrast, soy protein was effective in decreasing plasma triglyceride, as compared with levels in rats fed casein; this triglyceride-lowering effect was entirely abolished by methionine supplementation. The hypercholesterolemic effect of soy protein was characterized by a higher cholesterol content in low-density lipoprotein (LDL) and high-density lipoprotein 1 (HDL1) fractions, together with a marked induction of hepatic hydroxymethyl glutaryl coenzyme A (HMG CoA) reductase activity and to a lesser extent cholesterol 7 alpha-hydroxylase. There was practically no induction of these enzymes, as compared with levels in rats fed casein diets, when the soy protein diet was supplemented with methionine. Very-low-density lipoprotein (VLDL) plus LDL susceptibility to peroxidation was higher in rats fed soy protein than in casein-fed rats, which could reflect in part the lack of sulfur amino acid availability, since methionine supplementation led to a partial recovery of lipoprotein resistance to peroxidation. These findings suggest that amino acid imbalance could be atherogenic by increasing circulating cholesterol and leading to a higher lipoprotein susceptibility to peroxidation.

Resistant starch is more effective than cholestyramine as a lipid-lowering agent in the rat.

Amylase-resistant starch (RS) represents a substrate for the bacterial flora of the colon, and the question arises as whether RS shares with soluble fibers common mechanisms for their lipid-lowering effects. It is uncertain whether a cholesterol-lowering effect depends basically on an enhanced rate of steroid excretion or whether colonic fermentations also play a role in this effect. In the present study, the effect of RS (25% raw potato starch), of a steroid sequestrant (0.8% cholestyramine), or both were compared on bile acid excretion and lipid metabolism in rats fed semipurified diets. RS diets led to a marked rise in cecal size and the cecal pool of short-chain fatty acids (SCFA), as well as SCFA absorption; cholestyramine did not noticeably affect cecal fermentation. Whereas cholestyramine was particularly effective at enhancing bile acid excretion, RS was more effective in lowering plasma cholesterol (-32%) and triglycerides (-29%). The activity of 3-hydroxy-3-methylglutaryl-CoA reductase was increased fivefold by cholestyramine and twofold by RS. This induction in rats fed RS diets was concomittant to a depressed fatty acid synthase activity. In rats fed the RS diet, there was a lower concentration of cholesterol in all lipoprotein fractions, especially the (d = 1.040-1.080) fraction high-density lipoprotein (HDL1), while those fed cholestyramine had only a significant reduction of HDL1 cholesterol. In contrast to cholestyramine, RS also depressed the concentration of triglycerides in the triglyceride-rich lipoprotein fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of propionate on fatty acid and cholesterol synthesis and on acetate metabolism in isolated rat hepatocytes.

In the present study the actual role of propionic acid in the control of fatty acid and cholesterol synthesis was investigated in isolated liver cells from fed rats maintained in the presence of near-physiological concentrations of glucose, glutamine and acetate. Using 3H2O for lipid labelling, propionate appears as an effective inhibitor of fatty acid synthesis and to a lesser extent of cholesterol synthesis, even at the lowest concentration used (0.6 mmol/l). Butyrate is a potent activator of both synthetic pathways, and the activating effect was not counteracted by propionate. Using 1-[14C]acetate, it was observed that propionate at a moderate concentration, or 1 mmol oleate/l, are both very effective inhibitors of 14C incorporation into fatty acid and cholesterol. This incorporation was drastically inhibited when propionate and oleate were present together in the incubation medium. The net utilization of acetate by rat hepatocytes was impaired by propionate, in contrast to oleate. 1-[14C]butyrate was utilized at a high rate for fatty acid synthesis, but to a lesser extent for cholesterol synthesis; both processes were unaffected by propionate. Intracellular citrate concentration was not markedly depressed by propionate, whereas it was strongly elevated by butyrate. In conclusion, propionate may represent an effective inhibitor of lipid synthesis when acetate is a major source of acetyl-CoA, a situation which is encountered with diets rich in readily-fermentable fibres. The present findings also suggest that propionate may be effective at concentrations close to values measured in vivo in the portal vein.

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.

Cecal fermentations in rats fed oligosaccharides (inulin) are modulated by dietary calcium level.

The influence of Ca on the fermentation of dietary oligosaccharides in the large intestine has been investigated in four groups of rats fed different semipurified diets: 1) fiber free, 3 g Ca/kg; 2) fiber free, 8 g Ca/kg; 3) 15% inulin, 3 g Ca/kg; or 4) 15% inulin, 8 g Ca/kg. The cecal fermentations were very low in rats fed the fiber-free diets and were not affected by the dietary Ca level. Rats fed the inulin diets had enlarged cecum with acidic fermentations, relatively rich in propionic acid. In this diet group rats adapted to the 3 g Ca/kg level had very acidic fermentations and depressed volatile fatty acid concentrations together with an accumulation of lactic acid (L and D isomers). Inulin diets brought about a rise in the crypt column height and in the activity of ornithine decarboxylase in cecal mucosa, especially in the 3 g Ca/kg diet group. There was considerable accumulation of insoluble Ca and Pi in the cecum of rats fed high-Ca diets. Inulin feeding increased the percentage of soluble Ca and Pi; Ca absorption from the cecum was also markedly higher in rats fed inulin and was influenced by the dietary Ca level. The concentrations of soluble bile acids were depressed in rats fed inulin diets, which enhanced the fecal excretion of bile acids. These effects were poorly altered by changes in the dietary Ca level. In vitro it appears that CaPi is effective in decreasing the solubility of bile salts, chiefly in acidic conditions. In conclusion there is in the large intestine a system of control of luminal pH, which involves the presence of insoluble Ca and Pi.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between fermentations and calcium in the cecum of rats fed digestible or resistant starch.

The present studies were undertaken to investigate the effects of the dietary calcium (Ca) level on the Ca balance and on large intestine physiology in rats fed diets providing carbohydrate as digestible wheat starch (DS) or resistant starch (RS). Resistant starch was a high-amylose maize starch. The Ca level ranged from a marginally sufficient level (3 g/kg) to a level in excess of nutritional requirements (6 g/kg). The cecal fermentations were more developed in rats fed RS diets and they were affected by the dietary Ca level, compared to rats fed the DS diets. In rats fed a low Ca RS diet, the cecal fermentations were more acidic than with a high Ca level and there was an accumulation of lactic acid together with depressed concentrations of short-chain fatty acids. There was a considerable accumulation of Ca and phosphate (Pi) in the cecum of rats fed the 6 g/kg level; on the other hand, the concentrations of minerals (Ca, Pi) were very low in the cecum of rats fed the low Ca RS diet. The proportion of soluble Ca in the cecum was markedly enhanced by active fermentations, especially in rats fed the high Ca RS diet (16.3 mmol/l). In rats fed the RS diet, there was a substantial absorption of Ca from the cecum, which was relatively proportional to the dietary Ca level. The above data suggest that in these rats, Ca absorption in the large intestine made a substantial contribution to the digestive balance, probably at the expense of absorption in the upper part of the intestine.(ABSTRACT TRUNCATED AT 250 WORDS)

Replacement of digestible wheat starch by resistant cornstarch alters splanchnic metabolism in rats.

Splanchnic metabolism was investigated in rats fed either a diet containing highly digestible wheat starch (DS diet) or amylase-resistant cornstarch (RS diet). In rats fed the latter diet, there was a considerable enlargement of the cecum and an increase in the production and absorption of volatile fatty acids (VFA), chiefly acetic and propionic acids. As a result, the major substrates absorbed from the digestive tract were glucose in rats fed the DS diet and both glucose and VFA in rats fed the RS diet. The liver removed about one-third of the absorbed glucose in rats fed the DS diet, whereas there was a slight release of glucose by the liver in rats fed the RS diet. Plasma insulin was higher in rats fed the DS diet, and there were smaller fluctuations of plasma insulin and liver glycogen between the fed and postabsorptive periods in rats adapted to the RS diet. In these animals, propionate was the major VFA taken up by the liver and approximately 50% of absorbed acetate was also removed by the liver. During the postabsorptive period, there was still a substantial contribution of VFA, especially propionate, to liver metabolism. A depressive effect of the RS diet on plasma triglycerides, cholesterol and free fatty acids was observed only during the postabsorptive period. Replacement of a large part of absorbed glucose by VFA apparently allows time for absorption of energy fuels to be extended and dampens the fluctuations of glucose metabolism during the light: dark cycle.

High propionic acid fermentations and mineral accumulation in the cecum of rats adapted to different levels of inulin.

The digestive and metabolic effects of inulin (from chicory) were studied in rats adapted to semipurified diets containing 0, 5, 10 or 20% inulin (wt/wt). Moderate levels of inulin (5-10%) did not significantly affect food intake or body weight gain. Dietary inulin resulted in considerably greater cecal fermentation and a significantly greater intraluminal concentration of propionate (peaking at 58.4 mmol/L). A lower concentration of acetate (42.6 mmol/L) was observed in rats fed 20% inulin. Lactic fermentations were observed in rats fed the 10 or 20% inulin diets. The cecal pool of volatile fatty acids tended to reach a plateau in rats fed diets containing more than 10% inulin (up to 600-700 mumol), but volatile fatty acid absorption was a slightly hyperbolic function of the dietary inulin level. Butyrate absorption was proportionally lower than that of propionate. Inulin-containing diets induced an enlargement of the cecal pool of calcium, phosphate and (to a lesser extent) magnesium. There was also an enhanced absorption of these divalent cations. The cecal pool of bile acids was greater in rats fed inulin, and this oligosaccharide displayed a slight hypocholesterolemic effect, even in rats fed the 5% inulin diet. However, plasma triglycerides were depressed only in rats fed the 20% inulin diet. In conclusion, inulin seems very effective in promoting propionic fermentation and in enhancing the calcium content of the large intestine. However, high levels of inulin (greater than 10%) may affect growth in rats and lead to acidic (pH 5.65) cecal fermentation.

Effects of soybean fiber on cecal digestion in rats previously adapted to a fiber-free diet.

This study was conducted to study digestion in rats of a diet containing soybean fiber (chiefly hemicellulose). The animals were first fed a fiber-free high starch diet for 7 d before receiving a 30% soybean fiber diet. There was a progressive change in the cecal pool of volatile fatty acids (VFA), up to approximately 1000 mumol, due to the enlargement of the cecum in conjunction with the rise of the VFA concentration, and the decrease in the cecal pH to 6. In rats fed the soybean fiber diet, the cecal concentrations of acetate and propionate increased with propionate reaching a very high value (approximately 50 mmol/L) after 22 d of dietary treatment. Butyrate concentrations first increased, then declined to about 10 mmol/L. Absorption of VFA was enhanced fivefold between d 2 and d 21 and was then 10-fold higher than in rats fed the fiber-free diet. The transfer of blood urea to the cecum increased in parallel with the enlargement of the cecum and there was a large rise of ammonia absorption after 8 d. There was a rapid increase in the cecal pool of phosphorus, whereas the cecal pools of calcium and magnesium significantly increased only after 8 d. The cecal absorption of calcium and magnesium increased very early, even when the cecal pool of these cations was not enhanced. The soybean fiber diet also elicited a strong induction of ornithine decarboxylase (ODC) in cecal mucosa, which was attenuated after 21 d of dietary treatment. Thymidine kinase was smaller than for ODC.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of diets rich in fermentable carbohydrates on plasma lipoprotein levels and on lipoprotein catabolism in rats.

This study was conducted to examine the effects of a combination of several dietary fibers (5% guar gum, 5% apple pectin, 15% wheat bran, 22% soybean fiber) and crude potato starch (23%) on plasma lipids and lipoproteins and on liver lipid concentration in rats fed a diet containing either 15% lard or 5% oil with or without dietary cholesterol/cholic acid. Male Wistar rats ate the test diets for 3 wk. The incorporation of fiber and crude potato starch into the diet resulted in a significant enlargement of the cecum; it also increased the concentration of volatile fatty acids and the pool of acetate, propionate and butyrate. Feeding this fermentable carbohydrate decreased plasma cholesterol and triglyceride levels in rats given a low fat diet and prevented the expected rise in plasma cholesterol and triglycerides in rats fed cholesterol/cholic acid or lard. Further studies of high density lipoprotein (HDL) composition, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoA reductase) activity and 125I-labeled human low density lipoprotein (LDL) turnover were done in the group fed the low fat diet without added cholesterol/cholic acid. The study of the HDL fraction in rats fed a diet rich in fermentable carbohydrates demonstrated a decrease in the HDL1 subpopulation and in the proportion of apolipoprotein E. Plasma clearance of intravenously injected 125I-labeled LDL was faster in rats fed this diet than in rats fed the fiber-free diet. In the liver, cholesterol and triglyceride levels were depressed whereas the activity of HMG-CoA reductase was increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of feeding fermentable carbohydrates on the cecal concentrations of minerals and their fluxes between the cecum and blood plasma in the rat.

This study was conducted to determine in rats to what extent fermentable carbohydrates alter the mineral composition of cecal contents and the absorption of the major cations. The carbohydrates studied were as follows: an oligosaccharide (lactulose, 10%); a soluble fiber (pectin, 10%); and an amylose-rich starch, incompletely broken down in the small intestine (amylomaize starch, 25 or 50%). All of these carbohydrates elicited a marked enlargement of the cecum, a drop of cecal pH and an increase in the volatile fatty acids (VFA) pool. With the lactulose diet, the VFA concentration was the lowest, whereas VFA absorption was similar to that observed with the 10% pectin or 25% amylomaize diets. From comparisons between germfree and conventional rats adapted to a fiber-free diet, it appears that VFA are required as counter anions to maintain high concentrations of cations, especially sodium. In conventional rats fed fermentable carbohydrates, sodium concentration in the cecal fluid was approximately 80 mM, except with the lactulose diet (49.5 mM), due to osmotic effects of lactulose. There was, compared to the fiber-free diet, an increase in the cecal concentrations of potassium, calcium and phosphate, but not of magnesium; nevertheless, the cecal pool of all of these minerals was considerably increased. Potassium absorption was increased by fermentable carbohydrates in the cecum, which also appears to be a major site of magnesium and calcium absorption. Thus, fermentable carbohydrates shift aborally the absorption of the major cations, and this point is especially interesting in regard to calcium, since an enhanced supply of calcium in the large bowel has been invoked for fiber effects on colonic carcinogenesis.

[Crossed aphasia in right-handed patients. II. Neuropsychological and neurolinguistic study of a case. Evolution over a 2 year period]. / Aphasie croisée chez les droitiers. II. Etude neurolinguistique et neuropsychologique d'un cas. Evolution sur deux ans.

We present an unusual case of crossed aphasia in a doctor who is totally right handed, following an infarction which almost completely destroyed his right hemisphere. The observations--linguistic and extra linguistic--during a study over two years are presented. The aphasia evolved in three stages, taking semiological and evolutive aspects not commonly met with. In speech and writing there were: 1. an oral agrammatism and a written dyssyntaxia in the initial stage; 2. the evolution of a non-fluent speech typically agrammatic leading to a jargonaphasia; 3. a dissociation between oral and written language, characterised by phonemic paraphasias in speech and dyssyntaxia in writing. Comprehension was good except for a verbal class called "empty signs" of language, in which the lexic which refers to the notion of space and time has a primary role. On an extra linguistic level some of the usual signs of right hemisphere lesions were present indicating disturbances of a spatial type. The patient could no longer grasp the concept of numerical value and showed severe difficulties in relation to time. On a linguistic level, the discussion is first considered from a typological point of view; this allows to compare our patient's disorders with a Broca's then with a conduction aphasia, Secondly, the discussion is considered from a semiological point of view, taking into consideration the 10 selected cases in the literature and adding our own; a semiological formula of crossed aphasia is given: agrammatism and/or dyssyntaxia + phonemic paraphasia and/or dysorthographia. A suggestion concerning the role of each hemisphere in the language of our patient is proposed: the possible role played by a congenital deafness in the right ear (discovered in the patient at the age of 8) to explain this abnormal hemispherical functional specialisation is discussed. Original comprehension difficulties concerning the time-space lexic are replaced by a perspective of a cognitive type. We conclude that in our patient, there was a "breakdown" of time and space which comes close to the "indifferenciation" of spatial order and time which Piaget has described in children.