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PubMed2004

Effect of increasing ruminal butyrate absorption on splanchnic metabolism of volatile fatty acids absorbed from the washed reticulorumen of steers.

Four steers fitted with a ruminal cannula and chronic indwelling catheters in the mesenteric artery, mesenteric vein, hepatic portal vein, hepatic vein, and the right ruminal vein were used to study the absorption and metabolism of VFA from bicarbonate buffers incubated in the temporarily emptied and washed reticulorumen. Portal and hepatic vein blood flows were determined by infusion of p-aminohippurate into the mesenteric vein, and portal VFA fluxes were calibrated by infusion of isovalerate into the ruminal vein. The steers were subjected to four experimental treatments in a Latin square design with four periods within 1 d. The treatments were Control (bicarbonate buffer) and VFA buffers containing 4, 12, or 36 mmol butyrate/kg of buffer, respectively. The acetate content of the buffers was decreased with increasing butyrate to balance the acidity. The butyrate absorption from the rumen was 39, 111, and 300 +/- 4 mmol/h for the three VFA buffers, respectively. The ruminal absorption rates of propionate (260 +/- 12 mmol/h), isobutyrate (11.4 +/- 0.7 mmol/h), and valerate (17.3 +/- 0.7 mmol/h) were not affected by VFA buffers. The portal recovery of butyrate and valerate absorbed from the rumen increased (P < 0.01) with increasing butyrate absorption and reached 52 to 54 +/- 4% with the greatest butyrate absorption. The liver responded to the increased butyrate absorption with a decreasing fractional extraction of propionate and butyrate, and with the greatest butyrate absorption, the splanchnic flux was 22 +/- 1% and 18 +/- 1% of the absorbed propionate and butyrate, respectively. The increased propionate and butyrate release to peripheral tissues was followed by increased (P < 0.05) arterial concentrations of propionate (0.08 +/- 0.01 mmol/kg) and butyrate (0.07 +/- 0.01 mmol/kg). Arterial insulin concentration increased (P = 0.01) with incubation of VFA buffers compared with Control and was numerically greatest with the greatest level of butyrate absorption. We conclude that the capacity to metabolize butyrate by the ruminal epithelium and liver is limited. If butyrate absorption exceeds the metabolic capacity, it affects rumen epithelial and hepatic nutrient metabolism and affects the nutrient supply of peripheral tissues.

Absorption↗
PubMed1984

Luteinizing hormone secretion after withdrawal of exogenous progestogen in heifers fed three levels of dietary energy.

As experiment was conducted with 15 Angus X Hereford heifers that were 16 mo of age at the time the experiment was initiated. The heifers were assigned randomly in equal numbers to be fed low (L), maintenance (M) or high (H) energy diets for 191 d. Overall average weight for heifers at the time the experiment was initiated was 294 +/- 6 kg. All heifers were exhibiting estrous cycles at regular intervals and estrus was synchronized using a progestogen implant (norgestomet) in combination with an injection of estradiol valerate and norgestomet before initiation of dietary treatments. Dietary treatments started at time of implant removal and this day was designated as d 0. Blood samples were collected every other day from d 150 to 160 and progesterone concentrations were quantified to evaluate estrous cycle activity. In order to resynchronize the reproductive state, all heifers were retreated with norgestomet implants and injected with the estradiol valerate and norgestomet combination on d 160. Implants were removed on d 170. Serial blood samples were collected for 4-h periods at 20-min intervals starting at 0, 10, 20 and 30 h after implant removal and luteinizing hormone (LH) concentrations were quantified. Progesterone was quantified in samples collected at daily intervals (170 to 191 d) to evaluate whether a normal estrous cycle occurred subsequent to removal of the implant. Four of five heifers in each of the L and M treatment groups were not cycling, whereas all heifers in the H treatment were cycling at the time of progestogen implantation on d 160.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Role of insulin and glucose on metabolite uptake by the hind half of beef steers.

Arterial and venous concentrations, extraction ratios and uptake of glucose, L-lactate and volatile fatty acids were measured in the hind half of four beef steers (340 to 360 kg) fitted with indwelling catheters in the posterior aorta and vena cava. The steers were fed hourly a pelleted, 85% concentrate diet. Treatments were control, iv infusion of insulin (1.4 IU/min) and iv infusion of glucose (149.4 mmol/h). Arterial blood concentration of glucose decreased from 3.23 mM (control) to 1.51 mM (insulin), then increased to 4.29 mM (glucose). Extraction ratio of glucose increased about threefold from 2.6 and of L-lactate decreased about fourfold from 9.2 during insulin infusion, then returned toward control values during glucose infusion. Extraction ratios of acetate (39), propionate (45) and butyrate (28) were similar among treatments. Uptake (two steers) of glucose from blood (mmol/h) increased from 38 (control) to 76 (insulin) and 99 (glucose). Uptake of acetate, propionate and butyrate from plasma (mmol/h) was, respectively, 105, 6.5, .93 (control); 170, 11.9, 3.53 (insulin) and 134, 10.9, 3.12 (glucose). Rates of uptake of glucose and propionate during control were slower (P less than .05) than rates during insulin or glucose infusion; nonsignificant changes in uptake of butyrate followed a similar pattern. Uptake of L-lactate tended to be inversely related to uptake of glucose. Treatments did not affect uptake of acetate or valerate. Uptake of all metabolites except valerate was positive, indicating net use by the hind half.

Animals↗
PubMed1977

Experimental and clinical data on Cyclabil.

The effects of a 2-phase preparation on the parameters of cycle function were studied in 14 normally menstruating women. The preparation, Cyclabil, is administered in a series of 11 tablets with 2.0 mg oestradiol valerate and 10 tablets with 2.0 mg oestradiol valerate in combination with 0.5 mg D,L-norgestrel. The cervical function, the spinnbarkeit of the cervical mucus and its crystallisability and, by means of RIA, FSH, LH, 17beta-oestradiol and the progesterone serum levels were determined continuously in a control cycle before the treatment, in the first and third treatment cycles and in a subsequent control cycle. The results show that no impairment of the normal cycle function were found during cyclical administration of the 2-phase preparation in 13 women. Two pregnancies occurred during the therapy. The process of ovulation was inhibited in one subject during the medication. 20 other women with pronounced premenopausal deficiency symptoms and cycle irregularities were treated with the 2-phase preparation for 6 months. Apart from the good cycle regulation, the deficiency symptoms were eliminated completely in 19 women and almost completely in 1 woman. Checks of the FSH, LH, 17beta-oestradiol and oestrone serum levels conducted at random during a medication cycle showed only a slight influence on the gonadotropin level. During the medication, E2 can be demonstrated in comparison to E1 at a ratio of 1:10.

Adult↗
PubMed1979

Serum testosterone, FSH/LH and urinary excretion of estrogens and corticoids during treatment with an injectable, longacting estrogen-DHEA preparation.

Ten weeks after total hysterectomy and bilateral salpingo-oophorectomy, nine women were treated with injections of Gynodian, composed of 4 mg estradiol valerate and 200 mg dehydroepiandrosterone enanthate, followed by injections of Primodian, composed of 4 mg estradiol valerate and 90.27 mg testosterone enanthate. Before commencement of treatment estimation of serum FSH, LH and testosterone, and analyses for total estrogen, 17-ketogenic steroids and fractionated 17-ketosteroids in 24-hour urine samples were carried out in all patients. The same serum and urine analyses were made 2 weeks after the first Gynodian injection and the first Primodian injection respectively. Serum testosterone concentrations did not change during treatment with Gynodian, whereas they rose markedly after administration of Primodian. Two weeks after the first injection of Gynodian and also of Primodian, the total estrogen excretion was only slightly increased in comparison with the value measured before start of treatment, and the serum FSH/LH ratio was only slightly depressed. The daily urinary excretion of 17-ketogenic steroids and of fractionated 17-ketosteroids were unchanged during treatment.

17-Ketosteroids↗
PubMed1984

Oral progesterone and estrogen/progestogen therapy. Effects of natural and synthetic hormones on subfractions of HDL cholesterol and liver proteins.

The pharmacokinetics of progesterone after oral administration were investigated. After a single dose of 100 mg, serum concentrations of progesterone around 50-60 nM and of 20 alpha-hydroxy-4-pregnene-3-one around 5-6 nM were recorded within 1-4 hours and elevated levels persisted for 8-12 hours. There were only minor changes in 17 alpha-hydroxyprogesterone concentrations and serum levels of androstenedione and cortisol were unaffected. A significant conversion of circulating progesterone into deoxy-corticosterone was demonstrated. During clinical treatment with oral progesterone the individual serum concentrations of this potent mineralocorticoid were closely correlated to the progesterone concentrations. This observation could be important as regards the etiology of certain clinical disorders characterized by fluid retention. According to competitive binding analyses there was no evidence that progesterone or medroxyprogesterone acetate could cause significant displacement of cortisol from corticosteroid-binding globulin during clinical treatment. The effects of natural and synthetic hormones upon subfractions of high density lipoprotein (HDL) cholesterol and liver proteins were followed in postmenopausal women during replacement therapy with various estrogen-progestogen combinations. The total serum cholesterol level was significantly reduced during treatment with all estrogen regimens. The concentrations of HDL cholesterol, HDL2 cholesterol, apolipoprotein A I and A II were increased in a dose-dependent pattern during unopposed estrogen therapy. The potency of 10 micrograms of ethinyl estradiol was estimated to be equivalent to 3-4 mg of estradiol valerate. Estrogen effects were significantly reversed by levonorgestrel 250 micrograms and also by medroxyprogesterone acetate 10 mg. During treatment with natural progesterone, no changes were recorded in HDL cholesterol or its subfractions. As compared with the lipoproteins, pregnancy zone protein and sex hormone binding globulin (SHBG) were found to be more sensitive to the alkylated than to the non-alkylated estrogen. Both levonorgestrel and medroxyprogesterone acetate clearly reduced SHBG levels after 3 months, whereas micronized progesterone had no such effect. While tamoxifen counteracted the therapeutic and metabolic effects of estrogen the sequential addition of estriol had no apparent influence. Unopposed estrogen treatment enhanced liver lecithin synthesis along pathway I, i.e. reduced the amount of stearic acid and increased the amount of palmitic acid. The effects were dose-dependent and no qualitative differences between ethinyl estradiol and estradiol valerate were recorded.

Administration, Oral↗
PubMed1991

Lipid metabolism in anaerobic ecosystems.

In anaerobic ecosystems, acyl lipids are initially hydrolyzed by microbial lipases with the release of free fatty acids. Glycerol, galactose, choline, and other non-fatty acid components released during hydrolysis are fermented to volatile fatty acids by the fermentative bacteria. Fatty acids are not degraded further in the rumen or other parts of the digestive tract but are subjected to extensive biohydrogenation especially in the rumen. However, in environments such as sediments and waste digestors, which have long retention times, both long and short chain fatty acids are beta-oxidized to acetate by a special group of bacteria, the H2-producing syntrophs. Long chain fatty acids can also be degraded by alpha-oxidation. Biotransformation of bile acids, cholesterol, and steroids by intestinal microorganisms is extensive. Many rumen bacteria have specific growth requirements for fatty acids such as n-valeric, iso-valeric, 2-methylbutyric, and iso-butyric acids. Some species have requirements for C13 to C18 straight-chain saturated or monoenoic fatty acids for growth.

Anaerobiosis↗
PubMed2000

Comparison of the efficacy and endometrial safety of two estradiol valerate/dienogest combinations and Kliogest for continuous combined hormone replacement therapy in postmenopausal women.

OBJECTIVE: To compare the efficacy and endometrial safety of two estradiol valerate/dienogest combinations with Kliogest in the treatment of postmenopausal symptoms. DESIGN: This was a double-blind, randomized, multicenter study. METHODS: Patients were randomized to estradiol valerate 2.0 mg/dienogest 2.0 mg (Climodien), estradiol valerate 2.0 mg/dienogest 3.0 mg (E2Val 2/DNG 3); or estradiol 2.0 mg/estriol 1.0 mg/norethisterone acetate 1.0 mg (Kliogest) once daily for 1 year. The primary efficacy variable was the Kupperman index. Endometrial safety was determined primarily by biopsy. RESULTS AND CONCLUSIONS: Climodien and E2Val 2/DNG 3 were therapeutically equivalent to Kliogest (mean changes in Kupperman index -20.1, -19.0 and -18.3, respectively). No statistically significant differences existed between treatment groups in the severity of postmenopausal symptoms. The incidences of endometrial atrophy were similar in all groups. Climodien appeared to be superior to Kliogest in terms of vaginal bleeding pattern, whereas E2Val 2/DNG 3 was associated with a slightly higher incidence and greater intensity of vaginal bleeding. The incidences of adverse events were similar in all groups. A greater proportion of women in the Kliogest and E2Val 2/DNG 3 groups experienced vaginal bleeding, whereas breast problems were more common with Climodien. Climodien and E2Val 2/DNG 3 induced desirable changes in insulin-like growth factor I (decrease) and sex hormone binding globulin (increase) that were not seen with Kliogest.

Biopsy↗
PubMed2003

Comparison of grass and legume silages for milk production. 2. In vivo and in sacco evaluations of rumen function.

Two experiments were conducted to investigate the basis for higher voluntary intakes and increased alpha-linolenic acid content in milk from cows offered clover silages. Six cows with rumen and duodenal cannulae were used in a four-period changeover-design experiment. Cows received 8 kg/d of dairy concentrate and had ad libitum access to one of six silage treatments: grass, red clover, white clover, alfalfa, and 50/50 (dry matter basis) mixtures of grass with red clover or white clover. The rumen fermentability of grass, red clover, white clover, and grass/red clover silages was also evaluated in a nylon bag study. Legume silages led to increased dry matter intake and milk production in comparison with grass silage. There was no significant effect of legume silages on rumen pH and volatile fatty acid concentrations, but a significant increase in rumen ammonia concentration with the legume silages, reflecting their higher protein content. The inclusion of white clover or alfalfa silage, but not red clover silage, in diets led to an increase in molar proportions of isobutyric, iso-valeric, and n-valeric acids in comparison with diets based on grass silage. Rumen fill was significantly lower, and rumen passage rates were significantly higher for cows offered alfalfa or white clover silages. However, the markedly different particle size distribution of rumen contents with these feeds suggests very different mechanisms for the high intake characteristics: high rates of particle breakdown and passage with alfalfa, and high rates of fermentation and passage with white clover. Microbial energetic efficiency (grams microbial N per kilogram organic matter apparently digested in the rumen) was highest for cows offered alfalfa silage, intermediate for clover silage, and lowest for cows offered grass silage. These differences reflect the higher rumen outflow rates for legume silages in comparison with grass silage. However, the effect of these differences on N-use efficiency (feed to milk) was probably quite small in comparison with effects of N intake. Although the biohydrogenation of alpha-linolenic acid was still high for red clover silage (86.1% compared with 94.3% for grass silage), there was a 240% increase in the proportion of alpha-linolenic acid passing through the rumen. This explains the increased recovery of alpha-linolenic acid from feed into milk with diets based on red clover silage.

Animal Feed↗
PubMed1975

Metabolism of liquid whey fed to sheep.

Digestion was studied with three groups of four sheep each fed alfalfa hay. Treatments were whey only, whey plus water, and water only. Digestibilities of dry matter for the three rations were 71.3, 69.7, and 62.9%. Digestibilities of whey solids calculated by difference was 86.9% for whey only and 81.6% for whey plus water. Twelve sheep were in three trials to determine the intake of whey, water, and hay consumption. They were assigned to whey only, whey plus water, and water only. Hay, whey, and water consumption was 1.89, 8.73, and 0; 1.88, 7.62, and 1.21; and 2.05, 0, and 6.07 kg per animal daily. Three mature fistulated wether sheep were fed 6 liters of liquid whey daily. Three mature fistulated wether sheep uere fed 6 liters of liquid whey daily, and three similar sheep were fed water only. Rumen liquor samples were taken for analysis of volatile fatty acids at 0, 3, and 6 h after whey feeding on each of three alternate days. Alfalfa hay (1.2 kg/animal daily) was fed after the 6-h sampling. Molar percentage of acetic and valeric acids were lower and for butyric acid was higher for sheep fed whey. Propionic acid, acetate:propionate ratio, and total concentration were not affected significantly by whey feeding. Acetic acid decreased from 0 to 3 h, then partly returned to the prefeeding level at 6 h. The reverse was true for butyric acid. Valeric acid and total concentration of volatile fatty acids decreased from 0 to 6 h. Effects of day were unexplained.

Animal Feed↗
PubMed1984

Effect of carbon-4 and carbon-5 volatile fatty acids on growth of mixed rumen bacteria in vitro.

Mixed ruminal bacteria (400 mg cells/liter) were incubated in artificial media containing ammonia, sodium carbonate, macrominerals, vitamins, sulfide, microminerals, acetate, propionate, and butyrate. When mixed carbohydrates (equal parts glucose, maltose, sucrose, cellobiose, and soluble starch) were added at 155 mg/liter per h for 10 h, average bacterial growth rate was slow, and dry weight yield was greater than 23%. Additions of isobutyrate, valerate, isovalerate, and 2 methylbutyrate had little influence on synthesis of bacterial dry weight, deoxyribonucleic acid, ribonucleic acid, or carbohydrate. When a timothy hay inoculum was used, isovalerate and 2 methyl-butyrate increased protein synthesis by 11.2 and 16.4%, but isobutyrate and valerate alone were without effect. All four acids combined increased bacterial protein by 18.7%. Responses with an inoculum of 60% concentrate and mixed hay were smaller and not statistically different from control incubations. Low concentrations of Trypticase (less than 250 mg/liter) improved efficiency of microbial protein synthesis from organic matter, but more was associated with decreased efficiency and utilization of extracellular ammonia.

Ammonia↗
PubMed1987

Effects of feeding or infusing ammonium salts of volatile fatty acids on ruminal fermentation, plasma characteristics, and milk production of cows.

Eight rumen-fistulated Holstein cows, averaging 77 d postpartum, were used in a replicated 4 X 4 Latin square design with 28-d periods to investigate the effect of ammonium salts of isobutyrate, 2-methylbutyrate, isovalerate, and n-valerate on animal performance and their possible mechanism(s) and site(s) of action. Each cow was fed ad libitum a complete mixed diet of 55% corn silage and 45% concentrate on a dry basis that was supplemented with 1.8 kg of premix daily. Treatments were 1) control, 2) ammonium salts of volatile fatty acids in premix, 3) ammonium salts of volatile fatty acids ruminally infused, or 4) ammonium salts of volatile fatty acids abomasally infused. Mean ruminal fluid pH and concentrations of ammonia and volatile fatty acids for treatment comparisons were not different. Plasma concentrations of isobutyrate, 2-methylbutyrate, and valerate differed among treatments, but there was no significant effect on dry matter intake, milk production, milk composition, or efficiency of feed utilization. Apparent nutrient digestibility; disappearance of dry matter, cellulose, and nitrogen from polyester bags suspended in the rumen; and plasma concentrations of glucose, free fatty acids, and growth hormone also were not significantly affected by treatment.

Abomasum↗
PubMed1994

Effect of mesenteric vein infusion of propionate on splanchnic metabolism in primiparous Holstein cows.

Our objective was to assess the effects of increased propionate supply on gut and liver function in lactating cows. Four multicatheterized, primiparous cows (30.4 +/- .5 kg/d of milk) were fed for ad libitum intake a diet of 50% alfalfa hay and 50% concentrate (20.6 +/- 1.9 kg/d of DM, 226 +/- 21 MJ/d of metabolizable energy, and 611 +/- 56 g/d of N). Each cow received intramesenteric infusions of NaCl (control) or Na-propionate (150 mmol/h of a 2.5 M solution) in a reversal design. After 72 h of infusion, blood flow (by indicator dilution) and net flux (venoarterial differences multiplied by blood flow) were measured across portal-drained viscera and the liver. Energy supply from feed consumed and from infusion was similar between treatments. Energy that was excreted as milk decreased with propionate infusion. Propionate infusion increased arterial concentration of propionate; decreased absorption of acetate, butyrate, and valerate; and decreased hepatic removal of L-lactate, butyrate, valerate, NEFA, and oxygen. Propionate infusion decreased splanchnic release of glucose and increased splanchnic release of acetate and alanine. Net flux of urea, BHBA, insulin, or glucagon was unaffected by treatments. Our data show a link between a greater proportion of energy supplied as propionate and decreased energy excreted as milk. This response was associated with decreased net removal of glucogenic and ketogenic substrates by the liver and increased supply of acetate for use by peripheral tissues.

Analysis of Variance↗
PubMed1998

Influence of maturity of grass silage and flaked corn starch on the production and metabolism of volatile fatty acids in dairy cows.

An experiment employing a Latin square design was used to quantify the effects of two stages of maturity of grass silage (early cut and late cut) and three concentrations of flaked corn starch (0, 2, and 4 kg) on the molar proportion of rumen volatile fatty acids (VFA), the production of rumen VFA, and the net fluxes of VFA in the splanchnic tissue of cows. The molar proportions of VFA in rumen fluid were similar for cows fed both silages. When the silage diets were supplemented with starch, the proportion of propionic acid increased for cows fed diets containing early cut grass silage, but no effects were found for cows fed diets containing late cut grass silage. Estimated gastrointestinal production of acetate, propionate, butyrate, and branched-chain fatty acids plus valerate was related to intake of metabolizable energy and organic matter fermented into VFA. The portal release of acetate was approximately 14% lower than the estimated production of acetate by cows fed diets containing early cut grass silage, but cows fed diets containing late cut grass silage showed a variable difference between estimated production and portal release (31, 24, and 15%, respectively) as starch supplementation increased. The portal release of butyrate plus beta-hydroxybutyrate and the release of branched-chain fatty acids plus valerate were approximately 70 and 25%, respectively, of the estimated gastrointestinal production. Propionate production was similar to the portal release of propionate. Net flux measurements in splanchnic tissue in combination with gastrointestinal digestion and kinetics provide information that increases the knowledge of pathways and metabolism and quantifies the availability of individual nutrients for milk production in dairy cows.

Animals↗
PubMed1984

Short-chain fatty acid fermentation products of plant fiber affect glucose metabolism of isolated rat hepatocytes.

Short-chain fatty acids (SCFA) produced during fermentation of plant fibers and absorbed from the colon may affect hepatic glucose metabolism. We examined the effects of different fatty acids on rates of glucose production and glycolysis in isolated rat hepatocytes. Acetate, butyrate, and long-chain fatty acids significantly increased glucose production from lactate. However, propionate and valerate significantly decreased glucose production from lactate. Whereas 5 mM butyrate increased the incorporation of [14C]lactate into [14C]glucose by 80%, 5 mM propionate produced a 67% decrease. Glycolysis was significantly decreased by acetate, butyrate, and long-chain fatty acids. However, propionate and valerate significantly increased glycolysis. Thus propionate, which inhibits hepatic acetate metabolism, acts to increase glucose use and decrease glucose production. Plant fibers may influence hepatic glucose metabolism via their SCFA metabolites.

Animals↗
PubMed1993

Evidence that estrogen binding sites are present in bone cells and mediate medullary bone formation in Japanese quail.

Studies were carried out in Japanese quail to characterize the binding of estrogen to bone cells and to determine whether induction of medullary bone by estrogen is mediated by estrogen receptors. First, attempts were made to identify specific, high affinity nuclear binding sites for estrogen with a nuclear exchange assay in oviduct and femora from laying female quail and in liver, kidney, and femora from adult male quail treated with estradiol valerate (2 mg per bird). High-affinity nuclear estrogen binding sites were detected in each of the tissues except femora. Second, estrogen binding sites in femora from male quail were localized by radioautography after treatment with 100 microCi of [3H]-17 beta-estradiol ([3H]-E). Estrogen binding sites were present at 1 and 3 h after administration of [3H]-E, and binding of the radiolabeled hormone was prevented by the simultaneous administration of an excess of radioinert estrogen. Third, estradiol valerate (.4 mg) was given as a bolus to adult male Japanese quail. Five days later, the quail had hypercalcemia due to accumulation of phosvitin in serum, had an extensive network of medullary bone at the femur midshaft, and had reduced cortical bone area. The nonsteroidal, anti-estrogen tamoxifen (2 mg/day) prevented estrogen-induced hypercalcemia, medullary bone formation, and reduction of cortical bone area. Fourth, the estrogen target cells in femora from adult male quail that were induced to differentiate to osteoblasts by estrogen treatment were located by [3H]-proline radioautography as early as 12 h following administration of the hormone. These results are interpreted as evidence that induction of medullary bone is a process mediated by estrogen receptor.

Animals↗
PubMed1975

Studies on lankacidin-group (T-2636) antibiotics. X. Microbial conversion of lankacidin-group antibiotics.

Lankacidin C, a component of lankacidin-group (T-2636) antibiotics, was esterified to lankacidin C 8-butyrate in the presence of methyl butyrate by culture broth and by cell-free extract of Bacillus megaterium IFO 12108. In addition, methyl isobutyrate, methyl valerate and methyl isovalerate served as acyl donors for the esterification, and lankacidin C 8-isobutyrate, lankacidin C 8-valerate and lankacidin C 8-isovalerate were formed respectively. Lankacidin C 8, 14-dibutyrate was hydrolyzed to lankacidin C 14-butyrate by the same organism.

Anti-Bacterial Agents↗
PubMed1999

Short-chain fatty acids and thyroid hormone interact in regulating enterocyte gene transcription.

BACKGROUND: Enterocyte differentiation is known to be regulated by a variety of extracellular compounds, among which are triiodothyronine (T3) and the short-chain fatty acids (SCFAs). Because several SCFAs are known to induce histone hyperacetylation, and T3 action has been recently linked to chromatin structure, we sought to investigate the interplay between SCFAs and T3 in regard to the enterocyte differentiation marker, intestinal alkaline phosphatase (IAP). METHODS: Caco-2 cells were transiently transfected with a reporter construct containing 2.4 kb of the human IAP gene 5' flanking region (IAP2.4CAT). Cotransfections were carried out with and without thyroid hormone receptor-1 (TR beta-1) or histone deacetylase-1 (HDAC-1) expression plasmids. Cells were treated with 5 mmol/L SCFAs (propionic, butyric, valeric, or caproic acids as propionate, butyrate, valerate, or caproate, respectively), with and without 10 nmol/L T3. Reporter gene activity was measured and the level of histone acetylation assessed by means of acid-urea-triton (AUT) gel assays. RESULTS: TR beta-1 cotransfection caused a marked decrease in IAP reporter gene activity, which is consistent with the well-known phenomenon of ligand independent repression (LIR), whereas T3 treatment reversed the LIR and caused further reporter gene activation. Treatment with SCFAs similarly resulted in a complete blockage of LIR, and, in fact, turned the TR beta-1 into a transcriptional activator, even in the absence of T3. Concomitant treatment with T3 and butyric acid produced an additive effect on IAP transactivation. In contrast, cotransfection with HDAC-1 attenuated the effects of SCFAs on IAP gene activation. AUT gel studies demonstrated histone hyperacetylation in response to SCFA treatment. CONCLUSION: One or more DNA cis-elements in the human IAP gene mediate ligand independent repression by the TR beta-1, an effect that can be entirely reversed by those SCFAs that induce histone hyperacetylation. In addition T3 and SCFAs can act in concert to induce IAP gene transcription, demonstrating an important link between triiodothyronine and histone hyperacetylation in regard to enterocyte-specific gene expression.

Alkaline Phosphatase↗