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PubMed1997

Acarbose enhances human colonic butyrate production.

Earlier studies suggest that butyrate has colonic differentiating and nutritional effects and that acarbose increases butyrate production. To determine the effects of acarbose on colonic fermentation, subjects were given 50-200 mg acarbose or placebo (cornstarch), three times per day, with meals in a double-blind crossover study. Fecal concentrations of starch and starch-fermenting bacteria were measured and fecal fermentation products determined after incubation of fecal suspensions with and without added substrate for 6 and 24 h. Substrate additions were cornstarch, cornstarch plus acarbose and potato starch. Dietary starch consumption was similar during acarbose and placebo treatment periods, but fecal starch concentrations were found to be significantly greater with acarbose treatment. Ratios of starch-fermenting to total anaerobic bacteria were also significantly greater with acarbose treatment. Butyrate in feces, measured either as concentration or as percentage of total short-chain fatty acids, was significantly greater with acarbose treatment than with placebo treatment. Butyrate ranged from 22.3 to 27.5 mol/100 mol for the 50-200 mg, three times per day doses of acarbose compared with 18.3-19.3 mol/100 mol for the comparable placebo periods. The propionate in fecal total short-chain fatty acids was significantly less with acarbose treatment (10.7-12.1 mol/100 mol) than with placebo treatment (13.7-14.2 mol/100 mol). Butyrate production was significantly greater in fermentations in samples collected during acarbose treatment, whereas production of acetate and propionate was significantly less. Fermentation decreased when acarbose was added directly to cornstarch fermentations. Acarbose effectively augmented colonic butyrate production by several mechanisms; it reduced starch absorption, expanded concentrations of starch-fermenting and butyrate-producing bacteria and inhibited starch use by acetate- and propionate-producing bacteria.

Acarbose↗
PubMed1999

Secretion of phospholipid transfer protein by human hepatoma cell line, Hep G2, is enhanced by sodium butyrate.

Hep G2 cells were used to study the synthesis and secretion of phospholipid transfer protein (PLTP). Upon incubation of the cells at confluence with serum-free Dulbecco's modified Eagle's medium (DMEM), phosphatidylcholine (PC) transfer activity was found to accumulate in the culture media. The PC transfer activity in the media was effectively inhibited by rabbit anti-human PLTP immunoglobulin (Ig)G, thus indicating that the PC transfer activity was due to secreted PLTP. The molecular weight of Hep G2 PLTP was approximately 78 kDa by Western blot analysis, in agreement with the molecular weight obtained for purified human plasma PLTP. The PLTP secreted by Hep G2 also possessed an HDL conversion activity similar to that of human plasma PLTP. The addition of butyrate to the cell culture media resulted in a marked increase in the secretion of PLTP. After 24 h incubation with 4 mmol/L sodium butyrate, a more than twofold increase (P < 0.01) of PC transfer activity in the cell-conditioned media was obtained. The dose-dependent increase in the PC transfer activity in the media upon butyrate treatment was well correlated (r = 0.80, P < 0.01) with that of PLTP mass as determined by immuno-slot blot analysis of cell-conditioned media. The increased secretion of PLTP by Hep G2 treated with sodium butyrate was accompanied by a greater increase in the level of PLTP mRNA in the cells as determined by ribonuclease protection assay. In the presence of 4 mmol/L sodium butyrate, a fourfold increase (P < 0. 01) in mRNA level was obtained at 24 h. No stabilizing effect of butyrate on PLTP mRNA was apparent upon treatment of the cultured cells with the RNA synthesis inhibitor, actinomycin D. Thus, the up-regulatory effect of butyrate on PLTP gene expression seemed to have occurred at the transcriptional level.

Animals↗
PubMed1999

Psyllium shifts the fermentation site of high-amylose cornstarch toward the distal colon and increases fecal butyrate concentration in rats.

We examined the combination effects of psyllium (PS) and resistant starch on large bowel short-chain fatty acids (SCFA). Rats were fed one of the following four diets: low amylose (LAS) or high amylose cornstarch diets (HAS, 50 g/kg diet) with or without 15 g PS/kg diet (LAS/PS and HAS/PS diets). HAS and/or PS were substituted for the same amounts of LAS in diets. Cecal butyrate concentrations were significantly higher in rats fed the HAS and HAS/PS diets than in those fed the LAS and LAS/PS diets. However, butyrate and total SCFA concentrations in rats fed the HAS diet decreased along the length of the colon and fecal butyrate concentration was reduced to one-third of that in the cecum. In contrast, the HAS/PS diet maintained higher butyrate concentrations throughout the large bowel. Fecal butyrate concentration in the HAS/PS diet-fed group significantly exceeded the sum of the concentrations in rats fed the LAS/PS and HAS diets. PS supplementation to the HAS diet significantly increased fecal starch excretion by 10 fold compared with that of rats fed the HAS diet. There was a positive correlation between fecal butyrate concentration and fecal starch excretion (r = 0.709, P < 0.0001). In a further experiment, ileorectostomized rats were fed the HAS and HAS/PS diets. From the difference in fecal starch excretion between normal and ileorectostomized rats, starch degradation by large bowel microflora in rats fed the HAS and HAS/PS diets was deduced to be 96% and 63%, respectively. These findings support the hypothesis that PS may delay the fermentation rate of HAS in the cecum and shift the fermentation site of HAS toward the distal colon, leading to the higher butyrate concentration in the distal colon and feces.

Amylose↗
PubMed1999

Oligo-L-methionine and resistant protein promote cecal butyrate production in rats fed resistant starch and fructooligosaccharide.

We examined the role of resistant protein and peptides in promoting cecal butyrate production in rats fed rapidly fermentable carbohydrates. Rats were fed diets containing raw potato starch (RPS, 200 g/kg diet) or fructooligosaccharide (FOS, 60 g/kg diet) with casein, soy or rice protein (250 g/kg diet) for 13 d. In rats fed RPS with casein, the major cecal organic acid was acetate (441 micromol), but lactate and succinate were also found in considerable amounts (324 micromol). Succinate was the major cecal organic acid (235 micromol) in rats fed FOS with casein. When rice protein was fed with RPS, the contribution of lactate was significantly lower and that of propionate tended to be higher (P < 0.1) than in rats fed casein. In rats fed rice protein with FOS, cecal butyrate and acetate were greater and cecal succinate was lower than in rats fed casein with FOS (P < 0.05). Despite the similar amounts of undigested protein in rice and soy proteins, soy protein did not similarly affect cecal butyrate in rats fed FOS or RPS. In another experiment, rats were fed diets containing high amylose cornstarch (HAS, 200 g/kg diet) with casein, casein + oligo-L-methionine (OM, 3 g/kg diet), soy protein, soy protein + OM (3 g/kg diet) or rice protein (250 g/kg diet) for 10 d. OM (digestibility, 31%) was substituted for the same amount of casein. Rats fed rice protein had greater cecal butyrate than rats fed casein (P < 0.05). OM supplementation to casein or soy protein increased cecal butyrate compared with rats fed casein or soy protein alone (P < 0.05). These data support our hypothesis that resistant protein and peptides promote cecal butyrate production and suggest that the differing potency of rice and soy proteins in promoting cecal butyrate production might be explained in part by the different amino acid composition of resistant protein.

Analysis of Variance↗
PubMed2001

Butyrate impairs energy metabolism in isolated perfused liver of fed rats.

This study was designed to test the effects of short-chain fatty acids (SCFA) with an even number of carbon atoms on hepatic energy metabolism. The effect of the SCFA was evaluated by measuring liver ATP content and oxygen consumption. The ATP content was evaluated using (31)P nuclear magnetic resonance in isolated liver from fed rats. In addition, respiratory activity (VO(2)) was assessed using Clark electrodes. The livers were perfused with acetate, butyrate or a medium chain length fatty acid, octanoate, at a concentration of 0.05--5.0 mmol/L. The addition of each substrate enhanced the rate of the net ATP consumption (V(i)), establishing a new ATP steady state that required a perfusion time of > or = 20 min, dependent on the chain length and concentration of the fatty acid (FA). The initial V(i) was unchanged for acetate and the ATP level stabilized at 58% of the initial level. Both butyrate and octanoate induced a dose-dependent increase in V(i). This may reflect an ATP-consuming process for the intracellular pH regulation observed during the acidosis associated with the beta-oxidation pathway. At the new steady state, the ATP concentration was approximately 45% of the initial level for both FA. VO(2) was both rapidly and reversibly increased, and the change was a function of butyrate or octanoate concentration and of the chain length. K(m) values were similar for butyrate and octanoate. Because all of the effects were similar for butyrate and octanoate, in contrast to acetate, we suggest that the impairment of the energy metabolism by butyrate resulted from an increase in the FADH(2)/NADH ratio due to beta-oxidation. In conclusion, the difference in the hepatic oxidation pathways of two products of intestinal fermentation (acetate and butyrate) explains their different actions on energy metabolism.

Acetates↗
PubMed2004

Role of Ca2+ in induction of neurotransmitter-related gene expression by butyrate.

We examined the effect of butyrate on neurotransmitter-related gene expression and calcium homeostasis in PC12 cells. Pretreatment with Ca2+ chelators (EGTA or BAPTA-AM) attenuated the butyrate-triggered accumulation of TH and ppEnk mRNA indicating that Ca2+ plays a role in butyrate-induced regulation of neuronal genes. Butyrate alone did not alter intracellular Ca2+ levels as determined by Fura-PE3 fluorescence; however, pretreatment with butyrate (18-24 h) reduced the first Ca2+ peak and prevented the second sustained rise in [Ca2+]i as induced by nicotine or ryanodine. In contrast, butyrate had no effect on Ca2+ transients when added shortly before or during nicotine or ryanodine stimulation. These results suggest that chronic butyrate exposure can modulate cell responses by affecting intracellular Ca2+ signaling.

Animals↗
PubMed2002

Butyrate and aspirin in combination have an enhanced effect on apoptosis in human colorectal cancer cells.

Laboratory and epidemiological studies suggest that butyrate, a metabolic product of microbial fermentation of dietary fibre, and aspirin, a non-steroidal antiphlogistic drug, both reduce the risk of developing colon cancer. Notably, few data exist on potential interactions of these two substances. In this study, the effects of a butyrate-aspirin combination on human colon cancer cells were compared with treatment with aspirin or butyrate alone. Both substances decreased proliferation and induced differentiation and apoptosis. Butyrate reduced mutant p53 expression, whereas aspirin did not affect p53 expression. Butyrate-induced apoptosis correlated with an increase in Bak expression and a decrease in the expression of Bcl-XL. Aspirin had no effect on the investigated apoptosis-controlling factors. The antiproliferative and pro-apoptotic effects of the butyrate-aspirin combination were markedly enhanced. The combination resulted in a stronger decrease in the expression of PCNA and cdk2. Our data suggest that the anticarcinogenic effect of aspirin might effectively be augmented by combination with the short-chain fatty acid butyrate.

Apoptosis↗
PubMed2003

Increasing fecal butyrate in ulcerative colitis patients by diet: controlled pilot study.

Topical butyrate has been shown to be effective in the treatment of ulcerative colitis (UC). Butyrate is derived from colonic fermentation of dietary fiber, and our aim was to study whether UC patients could safely increase the fecal butyrate level by dietary means. We enrolled 22 patients with quiescent UC (mean age, 44 years; 45% women; median time from last relapse, 1 year) in a controlled pilot trial lasting 3 months. The patients were instructed to add 60 g oat bran (corresponding to 20 g dietary fiber) to the daily diet, mainly as bread slices. Fecal short-chain fatty acids (SCFAs) including butyrate, disease activity, and gastrointestinal symptoms were recorded every 4 weeks. During the oat bran intervention the fecal butyrate concentration increased by 36% at 4 weeks (from 11 +/- 2 (mean +/- SEM) to 15 +/- 2 micromol/g feces) (p < 0.01). The mean butyrate concentration over the entire test period was 14 +/- 1 micromol/g feces (p < 0.05). Remaining fecal SCFA levels were unchanged. No patient showed signs of colitis relapse. Unlike controls, the patients showed no increase in gastrointestinal complaints during the trial. Yet patients reporting abdominal pain and reflux complaints at entry showed significant improvement at 12 weeks that returned to baseline 3 months later. This pilot study shows that patients with quiescent UC can safely take a diet rich in oat bran specifically to increase the fecal butyrate level. This may have clinical implications and warrants studies of the long-term benefits of using oat bran in the maintenance therapy in UC.

Adult↗
PubMed1999

Induction of human herpesvirus-8 DNA replication and transcription by butyrate and TPA in BCBL-1 cells.

Human herpesvirus-8 (HHV-8) is a gammaherpesvirus that is present primarily in a state of low level persistence in primary effusion lymphoma cell lines. Using BCBL-1 cells that harbour HHV-8 but lack Epstein-Barr virus, we demonstrate that sodium butyrate is much more effective than the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) at inducing high levels of class II and III virus transcription and viral DNA replication, but also initiates apoptosis. Apoptosis occurs prior to assembly of virions when high concentrations of butyrate (1-3 mM) are used, whereas reduction of butyrate concentration to 0.3 mM decreases the rate of apoptosis and results in production and secretion of enveloped virions that are visualized at high number by electron microscopy in approximately 20% of BCBL-1 cells. Butyrate induces much higher levels of multiple class II and class III transcripts than does TPA, including v-MIPI, v-IL-6, v-Bcl-2, vGPCR and ORF26. A decrease in concentration of butyrate from 3 to 0.3 mM delays the peak induction of these genes, but peak levels remain higher than peak levels in response to TPA. These studies indicate that the massive apoptosis induced by 3 mM butyrate could be diminished and delayed by reduction of butyrate concentration to 0.3 mM, thereby allowing expression of high levels of lytic-associated genes and production of high yields of HHV-8 virions.

Butyrates↗
PubMed2005

Anti-inflammatory properties of heat shock protein 70 and butyrate on Salmonella-induced interleukin-8 secretion in enterocyte-like Caco-2 cells.

Intestinal epithelial cells secrete the chemokine interleukin (IL)-8 in the course of inflammation. Because heat shock proteins (Hsps) and butyrate confer protection to enterocytes, we investigated whether they modulate Salmonella enterica serovar Enteritidis (S. serovar Enteritidis)-induced secretion of IL-8 in enterocyte-like Caco-2 cells. Caco-2 cells incubated with or without butyrate (0-20 m M, 48 h) were infected with S. serovar Enteritidis after (1 h at 42 degrees C, 6 h at 37 degrees C) or without prior heat shock (37 degrees C). Levels of Hsp70 production and IL-8 secretion were analysed using immunostaining of Western blots and enzyme-linked immunosorbent assay (ELISA), respectively. The cells secreted IL-8 in response to S. serovar Enteritidis and produced Hsp70 after heat shock or incubation with butyrate. The IL-8 secretion was inhibited by heat shock and butyrate concentrations as low as 0.2 m M for crypt-like and 1 m M for villous-like cells. In a dose-dependent manner, higher butyrate concentrations enhanced IL-8 secretion to maximal levels followed by a gradual but stable decline. This decline was associated with increasing production of Hsp70 and was more vivid in crypt-like cells. In addition, the higher concentrations abolished the heat shock inhibitory effect. Instead, they promoted the IL-8 production in heat-shocked cells even in the absence of S. serovar Enteritidis. We conclude that heat shock and low concentrations of butyrate inhibit IL-8 production by Caco-2 cells exposed to S. serovar Enteritidis. Higher butyrate concentrations stimulate the chemokine production and override the inhibitory effect of the heat shock. The IL-8 down-regulation could in part be mediated via production of Hsp70.

Butyrates↗
PubMed1981

Induction by butyrate of differentiated properties in cloned murine rhabdomyosarcoma cells.

A cell line derived from the murine rhabdomyosarcoma BW10139 (Dexter, Cancer Res. 37: 3136, 1977) was subcloned and examined with respect to growth and myogenic characteristics in the presence and absence of 1 mM butyrate. Without butyrate, these cells behave as typical transformed cells: they grow rapidly and chaotically, do not form multinucleated muscle fibers and have little or no creatine kinase activity. In the presence of 1 mM sodium butyrate or butyric acid, growth slows, cells become arranged in whorl patterns, and creatine kinase activities increase to levels comparable to those found in normal chick myoblasts immediately prior to cell fusion. The increase in creatine kinase activity is detectable within 2 h exposure to butyrate, reaches a maximum by 24 h, and the elevated level can be maintained for at least six weeks. The induction is reversible upon sequential addition, deletion, and readdition of butyrate to the culture medium. Isoenzyme analyses demonstrated that only the BB form of creatine kinase is induced; MM creatine kinase was not detected. Although formation of multinucleated cells increases after exposure to butyrate, no typical myotubes form. The results suggest that this rhabdomyosarcoma cell line can, under appropriate conditions, re-express some properties characteristic of skeletal muscle, but not the complete muscle phenotype.

Animals↗
PubMed2006

Characterization of the effects of butyric acid on cell proliferation, cell cycle distribution and apoptosis.

We examined concentration-dependent changes in cell cycle distribution and cell cycle-related proteins induced by butyric acid. Butyric acid enhanced or suppressed the proliferation of Jurkat human T lymphocytes depending on concentration. A low concentration of butyric acid induced a massive increase in the number of cells in S and G2/M phases, whereas a high concentration significantly increased the accumulation of cells in G2/M phase, suppressed the accumulation of cells in G0/G1 and S phases, and induced apoptosis that cell cycle-related protein expression in Jurkat cells treated with high levels of butyric acid caused a marked decrease in cyclin A, cyclin E, cyclin-dependent kinase 2 (CDK2), CDK4 and CDK6 protein levels in G0/G1 and S phases, with apoptosis induction, and a decrease in cyclin B, Cdc25c and p27KIP1 protein levels, as well as an increase in p21CIP1/WAF1 protein level, in the G2/M phase. Taken together, our results indicate that butyric acid has bimodal effects on cell proliferation and survival. The inhibition of cell growth followed by the increase in apoptosis induced by high levels of butyric acid were related to an increase in cell death in G0/G1 and S phases, as well as G2/M arrest of cells. Finally, these results were further substantiated by the expression profile of butyric acid-treated Jurkat cells obtained by means of cDNA array.

Apoptosis↗
PubMed1999

Regulation of AA-NAT and HIOMT gene expression by butyrate and cyclic AMP in Y79 human retinoblastoma cells.

Two key enzymes involved in the synthesis of melatonin, hydroxyindole-O-methyltransferase (HIOMT) and arylalkylamine N-acetyltransferase (AA-NAT), are present in Y79 human retinoblastoma cells. Under certain conditions these cells produce melatonin and secrete it into the culture medium. In a previous study, it was observed that melatonin levels increase dramatically over control levels after the addition of dibutyryl cyclic AMP (dbcAMP), whereas after treatment with butyrate melatonin levels decreased. The changes in melatonin levels appeared to be the result of increases in AA-NAT activity or decreases in HIOMT activity, following dbcAMP or butyrate treatment. In this study, mechanisms by which these agents influence HIOMT and AA-NAT gene expression were examined. Levels of AA-NAT and HIOMT RNA expression in response to treatment of Y79 cultures with 4 mM dbcAMP or 2 mM butyrate were measured by semi-quantitative reverse-transcription/polymerase chain reaction. Butyrate and dbcAMP showed no effect on AA-NAT gene expression, whereas HIOMT gene expression was reduced by treatment with these agents. Levels of beta-actin RNA were increased following dbcAMP or butyrate treatment. This analysis suggests that the reduction in HIOMT activity caused by dbcAMP or butyrate treatment is the result of a decrease in HIOMT RNA synthesis or accumulation. Conversely, since AA-NAT RNA levels were unaffected by dbcAMP or butyrate treatment, the increase in AA-NAT activity previously observed may be the result of changes in the activational state of the AA-NAT protein.

Acetylserotonin O-Methyltransferase↗
PubMed2003

Butyrate downregulates alpha2beta1 integrin: a possible role in the induction of apoptosis in colorectal cancer cell lines.

BACKGROUND: Integrins mediate cell matrix adhesion and regulate cell growth and survival. In colonic epithelial cells, alpha(2)beta(1) integrin controls glandular differentiation and proliferation. Butyrate stimulates differentiation and induces apoptosis in vitro. AIMS: We investigated whether butyrate induction of apoptosis was associated with perturbation of integrin mediated cell matrix adhesion. METHODS: Three colonic cancer cell lines (SW1222, SW620, LS174T) were studied. Adhesion to extracellular matrix proteins, expression of alpha(2)beta(1) integrin, and apoptosis were studied in adherent cells after treatment with 4 mM butyrate. RESULTS: Butyrate decreased the attachment to type I collagen in SW620 cells and type I and IV collagen in LS174T cells. The decreased cell attachment was associated with downregulation of alpha(2)beta(1) integrin and increased apoptosis in adherent cells. No changes in alpha(2)beta(1) expression or matrix adhesion were seen in SW1222 cells, which were also found to be less sensitive to butyrate induction of apoptosis. Downregulation of alpha(2)beta(1) integrin preceded the detection of apoptosis. CONCLUSION: Apoptosis induced by butyrate is associated with downregulation of expression and functional activity of alpha(2)beta(1) integrin. Perturbation of cell matrix adhesion may be a novel mechanism by which butyrate induces apoptosis in colorectal cancer cells.

Apoptosis↗
PubMed2003

Apical NHE isoforms differentially regulate butyrate-stimulated Na absorption in rat distal colon.

Bicarbonate and butyrate stimulate electroneutral Na absorption via apical membrane Na-H exchange (NHE) in rat distal colon. cAMP downregulates NHE-3 isoform and inhibits HCO3-dependent, but not butyrate-dependent, Na absorption. This study sought to determine whether 1) the apical membrane NHE-2 and NHE-3 isoforms differentially mediated HCO3- and butyrate-dependent Na absorption, and 2) cAMP had different effects on NHE-2 and NHE-3 isoforms. The effect of specific inhibitors of NHE-2 and NHE-3 isoforms (50 microM HOE 694 and 2 microM S3226, respectively) on unidirectional 22Na transepithelial fluxes performed across isolated mucosa from rat distal colon under voltage-clamp conditions was examined. HCO3 stimulation of Na absorption was inhibited by EIPA, a nonspecific inhibitor of all NHE isoforms, by S3226 and dibutyryl cAMP but not by HOE 694. In contrast, butyrate stimulation of Na absorption was not altered by dibutyryl cAMP and was not inhibited by HOE 694 in the absence of dibutyryl cAMP, but in the presence of dibutyryl cAMP was HOE694 sensitive. In contrast, S3226 inhibited butyrate-stimulated Na absorption in the absence of dibutyryl cAMP, but not in its presence. We conclude that 1) HCO3-stimulated Na absorption is mediated solely by NHE-3 isoform, whereas butyrate-stimulated Na absorption is mediated by either NHE-3 or NHE-2 isoform, and 2) dibutyryl cAMP selectively inhibits NHE-3 isoform but stimulates NHE-2 isoform. Dibutyryl cAMP does not inhibit butyrate-stimulated Na absorption as a result of its differential effects on NHE-2 and NHE-3 isoforms.

Animals↗
PubMed1999

Antagonism of CD95 signaling blocks butyrate induction of apoptosis in young adult mouse colonic cells.

There is great interest in utilizing butyrate as a chemopreventive agent for colon tumorigenesis because of its ability to promote apoptosis in colon tumor cell lines. Because CD95 (APO-1/Fas) transduces signals resulting in apoptosis, we tested the hypothesis that butyrate-dependent colonocyte apoptosis is mediated by this death receptor. Butyrate (1 mM) exposure for 24 h upregulated expression of Fas and its ligand in young adult mouse colon (YAMC) cells. To delineate the proapoptotic effect of butyrate and to avoid the confounding effects of detachment from the extracellular matrix, adherent cell apoptosis was monitored as loss of plasma membrane asymmetry and dissipation of mitochondrial membrane potential (DeltaPsi(mt)) by laser cytometry. Soluble Fas receptor protein (Fas:Fc chimera) and caspase inhibitors (z-VAD-fmk and z-IETD-fmk) blocked butyrate induction of apoptosis. Treatment with Fas agonistic antibody (clone Jo-2) significantly induced cell death, indicating that Fas in colonocytes is functional. In addition, butyrate promoted apoptosis by inducing loss of DeltaPsi(mt) and phospholipid asymmetry of the plasma membrane after 12 and 24 h of exposure, respectively, before cell detachment. Therefore, Fas receptor-dependent signal transduction is involved in butyrate induction of apoptosis in colonocytes.

Animals↗
PubMed2003

Amelioration of dextran sulfate colitis by butyrate: role of heat shock protein 70 and NF-kappaB.

Butyrate enemas have been demonstrated to ameliorate inflammation in ulcerative colitis. The mechanism of this protective effect of butyrate is not known, and this study examines the effect of butyrate on epithelial function, inducible heat shock protein 70 (HSP70) expression, and NF-kappaB activation in experimental colitis. Colitis was induced in rats by oral dextran sulfate sodium (DSS) and by butyrate or saline enemas. Mucosal barrier function was assessed by electrical resistance and [14C]mannitol permeability. HSP70 production was determined by [35S]methionine labeling, Western blot analysis, and immunohistochemistry. Activation of heat shock factors (HSFs) and NF-kappaB was evaluated by EMSA. Butyrate showed a significant protection against the decrease in cell viability, increase in mucosal permeability, and polymorphonuclear neutrophil infiltration seen in DSS colitis. Butyrate inhibited HSP70 expression in DSS colitis and also inhibited the activation of HSF and NF-kappaB. Thus butyrate enema was found to be cytoprotective in DSS colitis, an effect partly mediated by suppressing activation of HSP70 and NF-kappaB.

Animals↗
PubMed2002

Modulation of lipid synthesis, apolipoprotein biogenesis, and lipoprotein assembly by butyrate.

Short-chain fatty acids (SCFAs) are potent modulators of the growth, function, and differentiation of intestinal epithelia. In addition, high-fiber diets may protect against the development of atherosclerosis because of their cholesterol-lowering effects due, in large part, to SCFA production, liver sterol metabolism, and bile acid excretion. Although the small gut plays a major role in dietary fat transport and contributes substantially to plasma cholesterol and lipoprotein homeostasis, the impact of SCFAs on intestinal lipid handling remains unknown. In the present study, the modulation of lipid synthesis, apolipoprotein biogenesis, and lipoprotein secretion by butyrate was investigated in Caco-2 cells plated on permeable polycarbonate filters, which permit separate access to the upper and lower compartments of the monolayers. Highly differentiated and polarized cells (20 days of culture) were incubated for 20 h with 20 mM butyrate in the apical medium. In the presence of [14C]oleic acid, butyrate led to a significant reduction of secreted, labeled triglycerides (27%; P < 0.01) and phospholipids (25%; P < 0.05). Similarly, butyrate significantly decreased the incorporation of [14C]acetate into exported cholesteryl ester (49%; P < 0.005). As expected from these results, with [14C]oleic acid as a precursor, butyrate significantly (P < 0.05) diminished the delivery of radiolabeled chylomicrons and very low-density lipoproteins. In parallel, [35S]methionine pulse labeling of Caco-2 cells revealed the concomitant inhibitory effect of butyrate on the synthesis of apolipoproteins B-48 (28%; P < 0.05) and A-I (32%; P < 0.01). Collectively, our data indicate that butyrate may influence lipid metabolism in Caco-2 cells, thus suggesting a potential regulation of intestinal fat absorption and circulating lipoprotein concentrations.

Apolipoproteins↗