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.

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.

The effect of dietary guar gum (GG, 7.5%) on lipid metabolism and on bile acid secretion and reabsorption was investigated in rats adapted to cholesterol-free or 0.3% cholesterol diets. Compared with controls (fiber-free/cholesterol-free), rats fed cholesterol had significantly elevated plasma and liver cholesterol and triglyceride. In these rats, GG had a potent plasma cholesterol-lowering effect and also counteracted the liver accumulation of triglyceride and cholesterol esters. Fecal excretion of sterols, the major route of cholesterol elimination, was markedly enhanced by GG, especially in rats fed the cholesterol-containing diet (P < 0.001). The biliary bile acid flux into the small intestine was enhanced by dietary cholesterol (+30%) or GG (+52%) or both (P < 0.001). The fecal excretion of bile acids was significantly elevated by GG alone (+74%) and by dietary cholesterol (+190%). Small intestine reabsorption of bile acids appears to be significantly enhanced by GG, which also enhanced the transfer of bile acids into the large intestine, hence a greater fecal loss of steroids, although bile acid reabsorption was very effective in the cecum. GG feeding induced liver hydroxymethyl-glutaryl coenzyme A (HMG CoA) reductase, even in cholesterol-fed rats, as well as cholesterol 7 alpha-hydroxylase (P < 0.001). The cholesterol-lowering effect of GG thus appears to be mediated by an accelerated fecal excretion of steroids and a rise in the intestinal pool and biliary production of bile acids. Although liver HMG CoA reductase and cholesterol 7 alpha-hydroxylase are induced in parallel, this is not sufficient to compensate for fecal steroid losses.

The aim of the present study was to evaluate the effect of changes in dietary protein level on overall availability of amino acids for tissues. For this purpose, rats were adapted to diets containing various concentrations of casein (7.5, 15, 30, and 60%) and were sampled either during the postprandial or postabsorptive period. In rats fed the protein-deficient diet, glucogenic amino acids (except threonine) tended to accumulate in plasma, liver, and muscles. In rats fed high-protein diets, the hepatic balance of glucogenic amino acids was markedly enhanced and their liver concentrations were consistently depressed. This response was the result of a marked induction of amino acid catabolism (a 45-fold increase of liver threonine-serine dehydratase activity was observed with the 60% casein diet). The muscle concentrations of threonine, serine, and glycine underwent changes parallel to plasma and liver concentrations, and a significant reduction of glutamine was observed. During the postabsorptive period, adaptation to high-protein diets resulted in a sustained catabolism of most glucogenic amino acids, which accentuated the drop in their concentrations (especially threonine) in all the compartments studied. The time course of metabolic adaptation from a 60 to a 15% casein diet has also been investigated. Adaptation of alanine and glutamine metabolism was rapid, whereas that of threonine, serine, and glycine was delayed and required 7-11 days. This was paralleled by a relatively slow decay of liver threonine-serine dehydratase (T-SDH) activity in contrast to the rapid adaptation of pyruvate kinase activity after refeeding a high-carbohydrate diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Chicory inulin has been identified as an effective prebiotic to promote active fermentation and lactobacilli proliferation in the large intestine, and to enhance calcium (Ca) digestive absorption and deposition in bones. The aim of this study was to compare, in a growing rat model, the effects on digestive fermentations and mineral metabolism of diets containing 7.5% inulin, using either a purified native inulin ((NAT)Inulin) or a reformulated inulin ((REF)Inulin, based on a combination of short- and long chain fructans) or dehydrated chicory. All the inulin diets elicited a marked enlargement of the cecum and acidification of the cecal contents (P < 0.01) and these diets promoted succinic acid rich fermentation together with substantial amounts of short-chain fatty acids (SCFA), especially butyrate. After 1 month of adaptation, all the inulin diets strongly enhanced Ca absorption compared to controls (P < 0.01), but this effect was no more observed after 3 months of adaptation. Magnesium (Mg) absorption was stimulated by the inulin diets after 1 and 3 months experiment. Bone parameters were significantly affected by the chicory diet (enhanced distal bone mineral density and breaking load) whereas the purified inulin diets were less effective. In conclusion, with the present model, both (NAT)Inulin and (REF)Inulin exerted similar effects as to (1) cecal fermentation and profile of end-products of bacterial metabolism, (2) stimulation of Ca and Mg digestive absorption and (3) overall effects on bone parameters. The particular effects of the chicory crude fractions on digestive fermentation and bone parameters suggest possible synergisms between inulin-type fructans and other nutrients.