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At least 199 records · Page 11Linked to original sources
PubMed2003

Dose-response effects of intrauminal infusion of propionate on feeding behavior of lactating cows in early or midlactation.

The objective of this experiment was to evaluate whether dose-response effects of intraruminal infusion of propionate on feeding behavior and dry matter intake (DMI) differ by stage of lactation. Six cows in early lactation (EL) and six cows in midlactation (ML) were assigned to blocks in a duplicated 6 x 6 Latin square design experiment. Treatments were mixtures of sodium propionate and sodium acetate containing sodium propionate at 0, 20, 40, 60, 80, and 100% of total volatile fatty acids (VFA), infused into the rumen continuously for 18 h starting 6 h before feeding at a rate of 21.7 mmol of sodium VFA/min. All cows were ruminally cannulated prior to the experiment. The diet was formulated to contain 30% NDF, and dry cracked corn was the major source of starch. We hypothesized that hypophagic effects of propionate infusion were greater for EL compared with ML because of greater plasma concentration of nonesterified fatty acids (275 vs. 76 microMeq/L) and expected greater basal oxidative metabolism in the liver for EL compared to ML. Propionate infusion decreased DMI for EL and ML, but a quadratic effect of propionate infusion was observed for ML but not EL. This indicated a greater marginal reduction in DMI at higher doses of propionate for ML compared to EL, contrary to our hypothesis. Propionate infusion decreased meal size similarly for both stages of lactation, but linearly increased intermeal interval for ML but not EL. We speculate that lower milk yield for ML compared with EL (30.8 vs. 42.0 kg/d) decreased glucose demand by the mammary gland and increased the proportion of infused propionate oxidized in the liver for ML compared to EL.

3-Hydroxybutyric Acid↗
PubMed1998

Survival of a Salmonella typhimurium poultry isolate in the presence of propionic acid under aerobic and anaerobic conditions.

Propionic acid is commonly found as a fermentation product in the gastrointestinal tracts of food animals and has also been used to limit the microbial contaminants in animal feeds. Because propionic acid is known to have antibacterial activity, the propionic acid encountered by foodborne pathogens during their life cycles may play an important role in inhibiting the survival of the pathogens. The survival patterns of Salmonella typhimurium poultry isolate were determined both in aerobic and anaerobic tryptic soy broth (TSB; pH 5.0 or 7.0) containing various concentrations of propionic acid (0-200 mM). The levels of recovered cells were consistently greater at pH 7.0 compared to those at pH 5.0. For the first 4 days, the levels were significantly decreased by incubation under anaerobic conditions as compared to aerobic condition at pH 7.0 (P<0.05). However, there were fluctuations of cell populations with different patterns depending on both concentrations and growth conditions. To characterize the nature of the capability which allowed the cell multiplication following decreases in cell population during incubation at pH 7.0, the cells isolated from the outgrowth cultures were tested for survival in aerobic or anaerobic TSB (pH 5.0 or pH 7.0) containing propionic acid (50 mM). The outgrowth isolates did not show significant differences in the level of recovered cells in the presence of propionic acid when compared to the wild type strain (P>0.05), suggesting that the cells in the outgrowth cultures did not harbour mutation(s) conferring increased resistance to propionic acid. In addition, the level of recovered cells of isogenic rpoS mutant strain of S. typhimurium was not significantly different from that of the wild type strain in the same assay conditions (P<0.05). The results of this study show that the bactericidal activity of propionic acid on S. typhimurium can be affected by environmental conditions such as acidic pH levels and anaerobiosis in food materials and gastrointestinal tracts. However, S. typhimurium is also able to multiply in the presence of sublethal concentrations of propionic acid at neutral pH during prolonged incubation under both aerobic and anaerobic conditions.

Journal Article↗
PubMed1998

Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease. International COPD Study Group.

BACKGROUND: The efficacy of inhaled corticosteroids in the treatment of chronic obstructive pulmonary disease (COPD) remains controversial because of a lack of placebo-controlled studies. We compared the effect of inhaled fluticasone propionate with placebo in the treatment of patients with COPD. METHODS: We used a randomised, double-blind, placebo-controlled design. We enrolled from 13 European countries, New Zealand, and South Africa, 281 outpatient current or ex-smokers, aged between 50 and 75 years. They had a forced expiratory volume in 1 s (FEV1) of between 35% and 90% of predicted normal values, a ratio of FEV1 to forced vital capacity of 70% or less and bronchodilator reversibility of less than 15%, as well as a history of chronic bronchitis. Patients were randomly assigned fluticasone propionate 500 microg (n=142) or placebo (n=139) twice daily via a metered-dose inhaler for 6 months. The main outcome measures were the number of patients who had at least one exacerbation by the end of treatment, the number and severity of exacerbations, clinic lung function, diary card symptoms and peak expiratory flow and 6 min walking distance. FINDINGS: 51 (37%) patients in the placebo group compared with 45 (32%) in the fluticasone propionate group had had at least one exacerbation by the end of treatment (p=0.449). Significantly more patients had moderate or severe exacerbations in the placebo group than in the fluticasone propionate group (86% vs 60%, p<0.001). Diary-card and clinic morning peak expiratory flows improved significantly in the fluticasone propionate group (p<0.001, p=0.048, respectively), as did clinic FEV1 (p<0.001), forced vital capacity (p<0.001), and mid-expiratory flow (p=0.01). Symptom scores for median daily cough and sputum volume were significantly lower with fluticasone propionate treatment than with placebo (p=0.004 and p=0.016, respectively). At the end of treatment, patients on fluticasone propionate had increased their 6 min walking distance significantly more than those on placebo (p=0.032). Fluticasone propionate was tolerated as well as placebo, with few adverse effects and without a clinically important effect on mean serum cortisol concentration. INTERPRETATION: Fluticasone propionate may be of clinical benefit in patients with COPD over at least 6 months. Inhaled corticosteroids may have an important role in the long-term treatment of COPD.

Administration, Inhalation↗
PubMed1996

Fluticasone propionate improves quality of life in patients with asthma requiring oral corticosteroids.

BACKGROUND: Fluticasone propionate is a potent inhaled corticosteroid that is effective in improving pulmonary function and symptoms in patients with asthma. OBJECTIVE: To evaluate the effects of fluticasone propionate on quality of life in patients with severe asthma requiring oral corticosteroids. METHODS: A total of 96 patients with severe asthma participated in a randomized, double-blind, placebo-controlled, parallel-group, oral steroid-sparing study. Patients received fluticasone propionate aerosol, 750 or 1000 micrograms bid, or placebo for 16 weeks; 91 of these patients continued in a 1-year open-label study, in which everyone initially received fluticasone propionate, 1000 micrograms bid. At regular intervals, patients completed the Medical Outcomes Study Short Form-36 (SF-36), a general health status questionnaire measuring eight dimensions of quality of life, plus one question on change in health from the previous year. RESULTS: Compared with the US population, patients scored significantly lower at baseline for five of eight SF-36 dimensions (P < .01). After 16 weeks, patients receiving fluticasone propionate, 1000 micrograms, improved significantly (P < or = .02) in physical functioning, role-physical, general health, and change in health, compared with the placebo group. After 1 year of open-label treatment with fluticasone propionate, these improvements were maintained. SF-36 scores in the placebo group during the double-blind period either worsened or remained unchanged; however, when these patients were switched to fluticasone propionate during the open-label period, their SF-36 scores also improved. Forced expiratory volume in 1 second (FEV1) at the end of the double-blind period was positively correlated with mean quality of life scores on physical functioning, role-physical, vitality, social functioning, and change-in-health status. CONCLUSION: Health-related quality of life improved in patients with severe asthma following 16 weeks of treatment with fluticasone propionate, 1000 micrograms bid. These improvements were maintained during subsequent fluticasone propionate treatment over a 1-year period.

Administration, Oral↗
PubMed1994

Anaerobic degradation of propionate by a mesophilic acetogenic bacterium in coculture and triculture with different methanogens.

A mesophilic acetogenic bacterium (MPOB) oxidized propionate to acetate and CO(2) in cocultures with the formate- and hydrogen-utilizing methanogens Methanospirillum hungatei and Methanobacterium formicicum. Propionate oxidation did not occur in cocultures with two Methanobrevibacter strains, which grew only with hydrogen. Tricultures consisting of MPOB, one of the Methanobrevibacter strains, and organisms which are able to convert formate into H(2) plus CO(2) (Desulfovibrio strain G11 or the homoacetogenic bacterium EE121) also degraded propionate. The MPOB, in the absence of methanogens, was able to couple propionate conversion to fumarate reduction. This propionate conversion was inhibited by hydrogen and by formate. Formate and hydrogen blocked the energetically unfavorable succinate oxidation to fumarate involved in propionate catabolism. Low formate and hydrogen concentrations are required for the syntrophic degradation of propionate by MPOB. In triculture with Methanospirillum hungatei and the aceticlastic Methanothrix soehngenii, propionate was degraded faster than in biculture with Methanospirillum hungatei, indicating that low acetate concentrations are favorable for propionate oxidation as well.

Journal Article↗
PubMed2003

Twice weekly fluticasone propionate added to emollient maintenance treatment to reduce risk of relapse in atopic dermatitis: randomised, double blind, parallel group study.

OBJECTIVE: To explore the efficacy and safety of fluticasone propionate, cream and ointment, applied twice weekly in addition to maintenance treatment with emollients, in reducing the risk of relapse of chronic recurrent atopic dermatitis. DESIGN: Randomised, double blind, parallel group study of 20 weeks' duration. SETTING: Dermatology outpatient clinics (6 countries, 39 centres). PARTICIPANTS: Adult (aged 12-65) patients with moderate to severe atopic dermatitis who were experiencing a flare. METHODS: Participants applied fluticasone propionate (0.05% cream or 0.005% ointment; once or twice daily) regularly for four weeks to stabilise their condition. The patients whose disease was brought under control then continued into a 16 week maintenance phase, applying emollient on a daily basis with a bath oil as needed and either the same formulation of fluticasone propionate or its placebo base (emollient alone) twice weekly to the areas that were usually affected. MAIN OUTCOME MEASURE: Time to relapse of atopic dermatitis during maintenance phase. RESULTS: 376 patients entered the stabilisation phase, and 295 continued into the maintenance phase. After 16 weeks in the maintenance phase, the disease remained under control in 133 patients (87 using fluticasone propionate twice weekly, 46 using emollient alone), 135 (40 fluticasone propionate, 95 emollient) had experienced a relapse, and 27 had discontinued. Median time to relapse was six weeks for emollient alone compared with more than 16 weeks for additional fluticasone propionate. Patients who applied fluticasone propionate cream twice weekly were 5.8 times less likely (95% confidence interval 3.1 to 10.8, P < 0.001) and patients using fluticasone propionate ointment 1.9 times less likely (1.2 to 3.2, P=0.010) to have a relapse than patients applying emollient alone. The groups showed no differences in adverse events. CONCLUSION: After atopic dermatitis had been stabilised the addition of fluticasone propionate twice weekly to maintenance treatment with emollients significantly reduced the risk of relapse.

Adolescent↗
PubMed1994

Effect of fluticasone propionate on neutrophil chemotaxis, superoxide generation, and extracellular proteolytic activity in vitro.

BACKGROUND: Corticosteroids are widely used in the treatment of many inflammatory conditions but the exact mode of action on neutrophil function is uncertain. Fluticasone propionate is a new topically active synthetic steroid which can be measured in body fluids and which undergoes first pass metabolism. METHODS: The effects of fluticasone propionate on the function of neutrophils isolated from normal, healthy control subjects and on the chemotactic activity of sputum sol phase were assessed. RESULTS: Preincubation of neutrophils with fluticasone propionate reduced the chemotactic response to 10(-8) mol/l F-Met-Leu-Phe (FMLP) and to a 1:5 dilution of sputum sol phase in a dose dependent manner. Furthermore, when fluticasone propionate was added to sputum from eight patients with stable chronic obstructive bronchitis the chemotactic activity of a 1:5 dilution of the sol phase fell from a mean (SE) value of 22.2 (1.21) cells/field to 19.6 (0.89), 17.1 (0.74), and 11.9 (0.6) cells field at 1 mumol/l, 10 mumol/l, and 100 mumol/l, respectively. In further experiments fluticasone propionate preincubated with neutrophils inhibited fibronectin degradation by resting cells and by cells stimulated by FMLP (15.2% inhibition of resting cells, 5.1% inhibition of stimulated cells with 1 mumol/l fluticasone propionate, 24% and 18.7% inhibition respectively at 100 mumol/l fluticasone propionate. Fluticasone propionate had no effect on generation of superoxide anion by resting or stimulated cells. CONCLUSIONS: These results indicate that fluticasone propionate has a direct suppressive effect on several aspects of neutrophil function and may suggest a role for this agent in the modulation of neutrophil mediated damage to connective tissue.

Administration, Topical↗
PubMed2000

Inhaled fluticasone propionate. A pharmacoeconomic review of its use in the management of asthma.

UNLABELLED: Contemporary asthma management guidelines list inhaled corticosteroids as the preferred controller medication for patients with persistent asthma. Despite the availability of explicit guidelines, there is evidence that these agents are underused and that guidelines are not always adhered to. Fluticasone propionate is one of several inhaled corticosteroids used for the treatment of asthma. Like other agents of its class, its efficacy is backed by extensive clinical data. More recently, the quality of life of recipients of fluticasone propionate and its relative cost effectiveness have been investigated. A series of comparative analyses show that inhaled fluticasone propionate is more cost effective than oral zafirlukast and triamcinolone acetonide and slightly more cost effective than flunisolide in adult patients with asthma. Analyses used cost per symptom-free day and/or cost per successfully treated patient as outcome measures and were generally conducted from the perspective of the third-party payer. When administered at a microgram dose of half or less than budesonide (as is therapeutically appropriate), the cost effectiveness of fluticasone propionate was similar to or better than that of budesonide. In children, fluticasone propionate was more cost effective per treatment success compared with inhaled sodium cromoglycate. Quality-of-life assessments in patients with mild to moderate disease show that inhaled fluticasone propionate achieved improvements which were deemed to be clinically meaningful in patients with mild to moderate asthma; these changes were significantly greater than those achieved with oral zafirlukast, inhaled triamcinolone acetonide or placebo. Greater improvements were evident with inhaled fluticasone propionate in patients with severe disease. CONCLUSIONS: In addition to the considerable body of clinical evidence supporting the use of inhaled fluticasone propionate in patients with asthma, accumulating short term cost-effectiveness data also suggest that this agent can be administered for a similar or lower cost per outcome than other inhaled corticosteroids or oral zafirlukast. Importantly, the clinical benefits offered by fluticasone propionate in patients with persistent asthma are accompanied by clinically significant improvements in quality of life.

Administration, Inhalation↗
PubMed2004

Clobetasol propionate lotion in the treatment of moderate to severe plaque-type psoriasis.

Owing to its anti-inflammatory, antipruritic, vasoconstrictive, and immune-modulating properties, clobetasol propionate is used to treat psoriasis. This study was conducted to evaluate the efficacy, safety, and cosmetic acceptability of clobetasol propionate lotion compared with its vehicle and with clobetasol propionate cream in the treatment of moderate to severe plaque-type psoriasis. A total of 222 patients were treated. After 4 weeks of treatment, clobetasol propionate lotion was more efficient than vehicle lotion and of equivalent efficacy as clobetasol propionate cream. Cosmetic acceptability was significantly better with clobetasol propionate lotion than with clobetasol propionate cream. Clobetasol propionate lotion was efficient, safe, and well tolerated and offers a significantly higher cosmetic advantage in the treatment of moderate to severe plaque-type psoriasis compared with clobetasol propionate cream.

Administration, Topical↗
PubMed2005

Anaerobic metabolism of propionate by polyphosphate-accumulating organisms in enhanced biological phosphorus removal systems.

Propionate, a carbon substrate abundant in many prefermenters, has been shown in several previous studies to be a more favorable substrate than acetate for enhanced biological phosphorus removal (EBPR). The anaerobic metabolism of propionate by polyphosphate accumulating organisms (PAOs) is studied in this paper. A metabolic model is proposed to characterize the anaerobic biochemical transformations of propionate uptake by PAOs. The model is demonstrated to predict very well the experimental data from a PAO culture enriched in a laboratory-scale reactor with propionate as the sole carbon source. Quantitative fluorescence in-situ hybridization (FISH) analysis shows that Candidatus Accumulibacter phosphatis, the only identified PAO to date, constitute 63% of the bacterial population in this culture. Unlike the anaerobic metabolism of acetate by PAOs, which induces mainly poly-beta-hydroxybutyrate (PHB) production, the major fractions of poly-beta-hydroxyalkanoate (PHA) produced with propionate as the carbon source are poly-beta-hydroxyvalerate (PHV) and poly-beta-hydroxy-2-methylvalerate (PH2MV). PHA formation correlates very well with a selective (or nonrandom) condensation of acetyl-CoA and propionyl-CoA molecules. The maximum specific propionate uptake rate by PAOs found in this study is 0.18 C-mol/C-mol-biomass . h, which is very similar to the maximum specific acetate uptake rate reported in literature. The energy required for transporting 1 carbon-mole of propionate across the PAO cell membrane is also determined to be similar to the transportation of 1 carbon-mole of acetate. Furthermore, the experimental results suggest that PAOs possess a similar preference toward acetate and propionate uptake on a carbon-mole basis.

Bacteria, Anaerobic↗
PubMed1992

Propionate metabolism in cultured human cells after overexpression of recombinant methylmalonyl CoA mutase: implications for somatic gene therapy.

Strategies for somatic gene therapy must consider the metabolic consequences of expressing the recombinant gene product in addition to methods for gene transfer and expression. We describe studies of propionate metabolism in cultured cells transfected with methylmalonyl CoA mutase (MCM), the enzyme deficient in mut methylmalonic acidemia. Transfection of MCM into mut fibroblasts restores propionate metabolism to normal levels in a dose-dependent manner. Overexpression of MCM, or the addition of excess propionate, carnitine, or cobalamin, does not increase propionate metabolism in normal human fibroblasts, lymphoblasts, or hepatoma cells, although hepatic cells exhibit > 10-fold higher levels of propionate metabolism. Significantly, the restoration of propionate metabolism in mut fibroblasts is disproportionately greater than the efficiency of transfection, suggesting the presence of a cooperative phenomenon between cells. Intercellular participation in propionate metabolism is evident in cocultures of MCM-deficient and propionyl CoA carboxylase-deficient cells. We conclude that the liver is the preferred target for gene therapy of MCM deficiency because of its greater capacity for propionate metabolism and that cooperation between cells could enhance the biological effect of a subpopulation of cells transformed with recombinant MCM.

Amino Acid Metabolism, Inborn Errors↗
PubMed1989

Comparative aspects of propionate metabolism.

1. The catabolism of propionate has been studied extensively in vertebrates and the major pathway has been shown to be its derivatization to propionyl-CoA, carboxylation to D-methylmalonyl-CoA, isomerization to L-methylmalonyl-CoA and then conversion to succinyl-CoA via a vitamin B12 dependent methylmalonyl-CoA mutase. 2. By contrast, in all insect species studied to date, many of which do not contain detectable levels of vitamin B12, the major metabolic pathway of propionate is its conversion to 3-hydroxypropionate and then to acetate. Carbon-3 of propionate becomes the carboxyl carbon of acetate and carbon-2 of propionate becomes the methyl carbon of acetate. 3. A number of species of non-insect arthropods and other invertebrates contain relatively high levels of vitamin B12 and catabolize propionate by the same pathway as that of vertebrates. Under anoxic conditions, some invertebrates, including bivalves, convert succinate to propionate. 4. In plants, evidence has been presented for the metabolism of propionate to both acetate and succinate. Micro-organisms possess a myriad of pathways by which they produce and catabolize propionate.

Animals↗
PubMed1978

Factors determining the sequence of oxidative decarboxylation of the 2- and 4-propionate substituents of coproporphyrinogen III by coproporphyrinogen oxidase in rat liver.

Coproporphyrinogen oxidase (EC 1.3.3.3) catalyses the oxidative decarboxylation of the 2- and 4-propionate substituents of coproporphyrinogen III to form protoporphyrinogen IX. A 4-propionate-substituted porphyrinogen, harderoporphyrinogen, which is also a substrate for coproporphyrinogen oxidase, is formed during the reaction. Synthetic [(14)C]coproporphyrinogens III, specifically labelled in the carboxyl carbon atoms of either the 2- or 4-propionate substituents, were used to measure the rate of decarboxylation of each substituent by rat liver coproporphyrinogen oxidase. The experimental results, together with the recognition that in all known substrates of coproporphyrinogen oxidase only those propionate groups flanked by a specific arrangement of substituents are decarboxylated, indicate that the 4-propionate group of coproporphyrinogen III cannot be attacked until the 2-propionate group has been decarboxylated. Production of (14)CO(2) from the substrate labelled in the 2-propionate group therefore measures the formation of harderoporphyrinogen, whereas (14)CO(2) from the 4-propionate-labelled substrate measures protoporphyrinogen IX formation. The rate of harderoporphyrinogen formation is about twice that of protoporphyrinogen, and this ratio is unchanged by varying the concentration of coproporphyrinogen III or by competitive inhibition of the enzyme. When coproporphyrinogen III is present in an excess, two fractions of harderoporphyrinogen can be distinguished. One accumulates during the reaction, and the other, which is destined to become protoporphyrinogen IX, does not equilibrate with added harderoporphyrinogen. It is suggested that both decarboxylations take place at the same active centre, which becomes temporarily inaccessible to coproporphyrinogen III and added harderoporphyrinogen, and that the molecule rotates after the first decarboxylation to allow the second to take place.

Animals↗
PubMed1980

Net hepatic and splanchnic metabolism of lactate, pyruvate and propionate in dairy cows in vivo in relation to lactation and nutrient supply.

1. Circulating concentrations of glucose, propionate, lactate and pyruvate, and net exchange of these compounds across the liver and gut, were measured in lactating and non-lactating dairy cows (a) in the normal fed state, (b) before, during and after intravenous infusion of an aqueous solution of glucose, propionate or lactate (lactating cows only) in fed animals, and (c) before and during 6 days of food deprivation. 2. In the normal fed state, gut output of propionate, hepatic output of glucose and hepatic uptake of lactate were all higher in the lactating group. There was a net uptake of pyruvate across the liver in the lactating cows and a net output in the non-lactating cows. In the lactating cows there was a net uptake of lactate and pyruvate by the splanchnic bed (i.e. gut and liver combined). 3. In the lactating cows, the glucose and propionate infusions had the following effects: decrease in net hepatic uptake of lactate; a switch in pyruvate exchange across the liver from uptake to output; suppression of uptake of lactate and pyruvate by the splanchnic bed; increase in the magnitude of the liver (propionate uptake)/(glucose output) ratio. Lactate infusion did not affect hepatic propionate uptake. 4. Food deprivation increased hepatic extraction of lactate and pyruvate and decreased the liver (propionate uptake)/(glucose output) ratio in both groups. 5. It is concluded that mechanisms exist to ensure an inverse relationship between the availability to the cow of glucose or propionate and utilization by the splanchnic bed of endogenously derived lactate and pyruvate.

Animals↗
PubMed2000

Methylcitrate synthase from Aspergillus nidulans: implications for propionate as an antifungal agent.

Aspergillus nidulans was used as a model organism to investigate the fungal propionate metabolism and the mechanism of growth inhibition by propionate. The fungus is able to grow slowly on propionate as sole carbon and energy source. Propionate is oxidized to pyruvate via the methylcitrate cycle. The key enzyme methylcitrate synthase was purified and the corresponding gene mcsA, which contains two introns, was cloned, sequenced and overexpressed in A. nidulans. The derived amino acid sequence of the enzyme shows more than 50% identity to those of most eukaryotic citrate synthases, but only 14% identity to the sequence of the recently detected bacterial methylcitrate synthase from Escherichia coli. A mcsA deletion strain was unable to grow on propionate. The inhibitory growth effect of propionate on glucose medium was enhanced in this strain, which led to the assumption that trapping of the available CoA as propionyl-CoA and/or the accumulating propionyl-CoA itself interferes with other biosynthetic pathways such as fatty acid and polyketide syntheses. In the wild-type strain, however, the predominant inhibitor may be methylcitrate. Propionate (100 mM) not only impaired hyphal growth of A. nidulans but also synthesis of the green polyketide-derived pigment of the conidia, whereas in the mutant pigmentation was abolished with 20 mM propionate.

Amino Acid Sequence↗
PubMed1991

Interactions between propionate and amino acid metabolism in isolated sheep hepatocytes.

The purpose of the present study was to evaluate the contribution of various substrates to glucose synthesis in isolated sheep hepatocytes, and more specifically to quantify the contribution of propionate to gluconeogenesis. Liver cells from fed sheep have a very high capacity for propionate utilization and conversion into glucose. The gluogenicity of lactate or amino acids was very low in hepatocytes from fed sheep, but was significantly increased in hepatocytes from starved animals. Amino acids such as alanine or glutamine were characterized by a substantial utilization towards ureogenesis; whereas their conversion to glucose was very low. Propionate utilization and conversion into glucose was inhibited by butyrate, ammonia and especially ethanol (by up to 80%). Ethanol promoted a striking accumulation of intracellular malate in hepatocytes incubated with propionate (reaching 14.9 mumol/g cell) and led to a depletion of phosphoenolpyruvate; ethanol inhibition could be counteracted by pyruvate. Propionate and butyrate enhanced ureogenesis from ammonia in ruminant liver cells but their effects were not additive. Propionate also elicited a marked increase in cellular concentrations of phosphoserine and serine, particularly in the presence of ammonia; such effects could influence phospholipid metabolism in the liver. These findings emphasize the contribution of propionate, compared with the other glucogenic substrates, to glucose synthesis in ruminants and point to the possibilities of modulation of the glucogenicity of propionate by various substrates which may be present in portal blood.

Amino Acids↗
PubMed1993

The voluntary intake of hay and silage by lactating cows in response to ruminal infusion of acetate or propionate, or both, with or without distension of the rumen by a balloon.

In order to test the hypothesis that negative feedback signals from abdominal receptors are integrated in an additive manner in the control of voluntary food intake, cows with rumen fistulas were given intraruminal infusions of sodium acetate or sodium propionate, or both, with or without distension of the rumen by balloon. Intakes were monitored during the 3 h experimental period and for 2 h after and samples of rumen fluid were taken for estimation of short-chain fatty acid concentrations and osmolality. Six cows in mid-lactation were fed on hay and concentrates and given, into the rumen, 5.5 mol sodium acetate, 5.2 mol sodium propionate and 7.5 l of distension. Compared with the control (water infusion), neither acetate, propionate nor distension significantly depressed hay intake when given separately. When given in combination, however, the following significantly depressed intake during the 3 h treatment period: propionate + distension, acetate + distension, acetate + propionate + distension. Seven cows in early lactation were fed on silage and concentrates and given, into the rumen, 9.0 mol sodium acetate, 4.0 mol sodium propionate and 10.0 litres of distension. Again, none of the three given alone depressed silage intake to a significant extent during the 3 h treatment period, whereas the following combinations had a significant effect: propionate + distension, acetate + distension, acetate + propionate + distension. Basal rumen osmolalities were similar for the two types of feed but infusion of the sodium salts caused a very much greater increase with silage than with hay.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed1995

Differences in propionate-induced inhibition of cholesterol and triacylglycerol synthesis between human and rat hepatocytes in primary culture.

Propionate is a short-chain fatty acid formed in the colon and supposedly involved in the cholesterol-lowering effect of soluble fibre. To explore the underlying mechanism(s) of this fibre action, we have used human hepatocytes in primary culture to study the effects of propionate on hepatic lipid synthesis. Initial experiments with mevalonate and mevinolin, a competitive inhibitor of hydroxymethylglutaryl (HMG)-CoA reductase (EC 1.1.1.88) were performed to evaluate basic regulatory mechanisms in these cells; results were compared with those obtained with rat hepatocytes. Incubation for 24 h with mevalonate caused a similar, concentration-dependent inhibition of [14C]acetate incorporation into cholesterol in human and rat hepatocytes. Likewise, mevinolin (100 mumol/l) inhibited the formation of cholesterol from radiolabelled acetate by about 80% in cells from both species. Propionate inhibited cholesterol as well as triacylglycerol synthesis from [14C]acetate with a similar concentration-dependency in rat hepatocytes. Fifty percent inhibition was obtained at a propionate concentration of only 0.1 mmol/l. This propionate-induced inhibition was not affected by a 100-fold excess of unlabelled acetate. Human hepatocytes were much less susceptible in this respect: propionate concentrations of 10-20 mmol/l were required to obtain similar inhibitory effects in these cells, i.e. values greatly exceeding reported portal propionate concentrations in humans. The results suggest the existence of differences in the regulation of hepatic cholesterol (and triacylglycerol) synthesis between human and rat liver cells. These results do not support the hypothesis that the fibre-induced decrease in plasma cholesterol concentration in man is mediated by a direct effect of propionate on hepatic cholesterol synthesis.

Acetates↗