Injection Of Butyrate Research Articles

Effects of butyrate on intestinal ischemia-reperfusion injury via the HMGB1-TLR4-MyD88 signaling pathway.

This study combined bioinformatics and experimental verification in a mouse model of intestinal ischemia-reperfusion injury (IRI) to explore the protection mechanism exerted by butyrate against IRI. GeneCards, Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine and GSE190581 were used to explore the relationship between butyrate and IRI and aging. Protein-protein interaction networks involving butyrate and IRI were constructed via the STRING database, with hub gene analysis performed through Cytoscape. Functional enrichment analysis was conducted on intersection genes. A mouse model of IRI was established, followed by direct arterial injection of butyrate. The experiment comprised five groups: normal, sham, model, vehicle, low-dose butyrate, and high-dose butyrate. Intestinal tissue observation was done via transmission electron microscopy (TEM), histological examination via hematoxylin and eosin (H&E) staining, tight junction proteins detection via immunohistochemistry, and Western blot analysis of hub genes. Drug-target interactions were evaluated through molecular docking. Butyrate protected against IRI by targeting 458 genes, including HMGB1 and TLR4. Toll-like receptor pathway was implicated. Butyrate improved intestinal IRI by reducing mucosal damage, increasing tight junction proteins, and lowering levels of HMGB1, TLR4, and MyD88. Molecular docking showed strong binding energies between butyrate and HMGB1 (-3.7 kcal/mol) and TLR4 (-3.8 kcal/mol). According to bioinformatics predictions, butyrate mitigates IRI via multiple-target and multiple-channel mechanisms. The extent of IRI can be reduced by butyrate through the inhibition of the HMGB1-TLR4-MyD88 signaling pathway, which is related to senescence.

Abstract P320: The Gut Microbial Metabolite Butyrate Suppresses Cardiac Hypertrophy Via An Epigenetic Mechanism

Introduction: Short-chain fatty acids (SCFA) are one of the gut microbial metabolites that can influence host health and disease. We previously reported that gut dysbiosis is associated with heart failure, and that the proportion of butyrate-producing bacteria is decreased in the gut of patients with heart failure. Purpose: We investigated the molecular mechanism of butyrate in the development of cardiac hypertrophy. Methods and Results: Single-cell transcriptome analysis and co-expression network analysis revealed that G protein-coupled receptors for short-chain fatty acid receptors were not expressed in cardiomyocytes and that Olfr78 was expressed in vascular smooth muscle cells in the heart. On the other hand, treatment with butyrate inhibited ET1-induced and isoproterenol (ISO)-induced hypertrophic growth in cultured neonatal rat cardiomyocytes. Moreover, butyrate increased the acetylation levels of histone H3, suggesting the inhibitory effect of butyrate on HDAC. In addition, butyrate caused the degradation of HDAC2 and up-regulation of Inpp5f, encoding inositol polyphosphate-5-phosphatase f, leading to a significant decrease in the phosphorylation levels of Akt and glycogen synthase kinase 3β (GSK3β). Finally, intraperitoneal injection of butyrate inhibited ISO-induced cardiac hypertrophy in mice. These results suggest that butyrate protects against hypertrophic responses via suppression of the Akt-GSK3β pathway through HDAC inhibition. Conclusion: In the heart, there were no known short-chain fatty acid receptors in cardiomyocytes. However, butyrate was shown to have an epigenetic mechanism in suppressing effect on cardiomyocyte hypertrophy via suppression of HDAC2-Akt-GSK3β axis. Our results uncover a potential link between dysbiosis of intestinal microbiota and the development of cardiac hypertrophy.

Centrally administered butyrate improves gut barrier function, visceral sensation and septic lethality in rats

Short chain fatty acids readily crosses the gut-blood and blood–brain barrier and acts centrally to influence neuronal signaling. We hypothesized that butyrate, a short-chain fatty acid produced by bacterial fermentation, in the central nervous system may play a role in the regulation of intestinal functions. Colonic permeability and visceral sensation was evaluated in rats. Septic lethality was evaluated in a sepsis model induced by subcutaneous administration of both lipopolysaccharide and colchicine. Intracisternal butyrate dose-dependently improved colonic hyperpermeability and visceral nociception. In contrast, subcutaneous injection of butyrate failed to change it. Intracisternal orexin 1 receptor antagonist or surgical vagotomy blocked the central butyrate-induced improvement of colonic hyperpermeability. The improvement of intestinal hyperpermeability by central butyrate or intracisternal orexin-A was blocked by cannabinoid 1 or 2 receptor antagonist. Intracisternal butyrate significantly improved survival period in septic rats. These results suggest that butyrate acts in the central nervous system to improve gut permeability and visceral nociception through cannabinoid signaling. Endogenous orexin in the brain may mediate the reduction of intestinal hyperpermeability by central butyrate through the vagus nerve. We would suggest that improvement of leaky gut by central butyrate may induce visceral antinociception and protection from septic lethality.

Gut Microbiota Manipulation Promotes Bone Homeostasis in Obese Mice Through Regulatory T-Cell Differentiation

A better understanding of the role of the gut microbiome in regulating skeletal metabolism has recently been reported. Manipulation of the gut microbiome with probiotics can prevent pathologic bone loss. However, the effects of probiotics/gut microbiota on immunomodulatory effect and skeletal homeostasis in the high fat diet (HFD)-linked obesity remains to be explored. Here, we examined the impact of supplementation with probiotics (VSL#3) on immune function and bone homeostasis in HFD mice. µ-CT and mechanical testing revealed that probiotics induced a significant increase of trabecular bone volume and bone mechanical strength in obese mice. Butyrate produced in the gut following probiotics treatment, or butyrate injection directly to obese mice, prevented gut inflammation, improved gut-barrier integrity, and induced the expansion of bone marrow (BM) regulatory T (Treg) cells. Mechanistically, probiotics treatment promoted the Kdm6b/Jmjd3 histone demethylase dependent Tfam promoter demethylation by inhibiting the H3K27me3 epigenetic mark in Treg cells, which increases Tfam expression. Reduced Tfam expression in Treg cells, were found to secrete greater concentration of mtDNA and modulate paracrine signaling. BMMSCs expressed DEC205 that bound to mtDNA and contributed to BMMSCs inflammation. Further, Tfam-transgenic mice, fed with HFD, prevented the obesity-linked reduction in Treg cells and mtDNA-DEC205 dependent BMMSC inflammation. Moreover, fecal transplantation from healthy, probiotic-treated donor mice is sufficient to improve gut barrier permeability and bone loss, suggesting that the probiotics mediated changes in the gut microbiome and may be a novel agent to regulate bone anabolism via the gut-immune axis.

Butyrate, a metabolite of intestinal bacteria, enhances sleep

Emerging evidence suggests that the intestinal microbiota is a source of sleep-promoting signals. Bacterial metabolites and components of the bacterial cell wall are likely to provide important links between the intestinal commensal flora and sleep-generating mechanisms in the brain. Butyrate is a short-chain fatty acid produced by the intestinal bacteria by the fermentation of nondigestible polysaccharides. We tested the hypothesis that butyrate may serve as a bacterial-derived sleep-promoting signal. Oral gavage administration of tributyrin, a butyrate pro-drug, elicited an almost 50% increase in non-rapid-eye movement sleep (NREMS) in mice for 4 hours after the treatment. Similarly, intraportal injection of butyrate led to prompt and robust increases in NREMS in rats. In the first 6 hours after the butyrate injection, NREMS increased by 70%. Both the oral and intraportal administration of butyrate led to a significant drop in body temperature. Systemic subcutaneous or intraperitoneal injection of butyrate did not have any significant effect on sleep or body temperature. The results suggest that the sleep-inducing effects of butyrate are mediated by a sensory mechanism located in the liver and/or in the portal vein wall. Hepatoportal butyrate-sensitive mechanisms may play a role in sleep modulation by the intestinal microbiota.

Short-chain fatty acids suppress food intake by activating vagal afferent neurons

Fermentable carbohydrates including dietary fibers and resistant starch produce short-chain fatty acids (SCFAs), including acetate, propionate and butyrate, through microbial fermentation in the intestine of rodents and humans. Consumption of fermentable carbohydrate and SCFAs suppress food intake, an effect involving the brain. However, their signaling pathway to the brain remains unclear. Vagal afferents serve to link intestinal information to the brain. In the present study, we explored possible role of vagal afferents in the anorexigenic effect of SCFAs. Intraperitoneal (ip) injection of three SCFA molecules (6 mmol/kg) suppressed food intake in fasted mice with the rank order of butyrate > propionate > acetate. The suppressions of feeding by butyrate, propionate and acetate were attenuated by vagotomy of hepatic branch and blunted by systemic treatment with capsaicin that denervates capsaicin-sensitive sensory nerves including vagal afferents. Ip injection of butyrate induced significant phosphorylation of extracellular-signal-regulated kinase 1/2, cellular activation markers, in nodose ganglia and their projection site, medial nucleus tractus solitaries. Moreover, butyrate directly interacted with single neurons isolated from nodose ganglia and induced intracellular Ca2+ signaling. The present results identify the vagal afferent as the novel pathway through which exogenous SCFAs execute the remote control of feeding behavior and possibly other brain functions. Vagal afferents might participate in suppression of feeding by intestine-born SCFAs.

Butyrate reduces appetite and activates brown adipose tissue via the gut-brain neural circuit

ObjectiveButyrate exerts metabolic benefits in mice and humans, the underlying mechanisms being still unclear. We aimed to investigate the effect of butyrate on appetite and energy expenditure, and to what...

Microbial Metabolite, Butyrate, Increases Blood Pressure in Rodent Models of Hypertension

IntroductionThe emerging link between gut dysbiosis and hypertension is characterized by a significant reduction in butyrate‐producing bacteria in the spontaneously hypertensive rat (SHR) compared with the Wistar Kyoto (WKY) control. Butyrate, a major end product of dietary fiber fermentation by gut microbiota, reportedly produces beneficial effects in multiple dysbiosis‐related diseases. However, butyrate has also been linked with activation of the sympathetic drive, elevated heart rate and release of norepinephrine. Considering the established link between sympathetic drive and hypertension, we investigated the role of butyrate in blood pressure (BP) control in hypertension.MethodsMale SHR (5 wo) were placed on either the fiber‐rich (butyrolytic) diet (SHR‐BD) or control diet (SHR‐CD) for 13 weeks ad libitum. Fecal/cecal butyrate levels were determined using high performance liquid chromatography (HPLC) throughout the study. Following this, fecal matter transplant (FMT) from both groups was performed separately to male WKY recipients (7 wo) with antibiotic‐depleted endogenous gut bacteria, to create two groups: WKY FMT‐BD and WKY FMT‐CD. Five weeks following FMT, both groups were infused with a subpressor dose of angiotensin II (Ang II; 50ng/kg/min) for three weeks. Separate male SHR (9 wo) were administered with daily injections of either saline or butyrate (500mg/kg/day I.P.) for four weeks. BPs were measured in all groups using tailcuff or telemetry throughout the study.ResultsElevated cecal butyrate in SHR‐BD (by 2 fold vs. SHR‐CD; P<0.001) was associated with significantly higher SBP (SHR‐CD: 183.3mmHg vs SHR‐BD: 206.6 mmHg; P<0.01). FMT from SHR‐CD and SHR‐BD caused a similar BP increase in the WKY recipients (ΔSBP=11.5 mmHg, P<0.001), However, a subsequent administration of subpressor Ang II further elevated SBP in the WKY FMT‐BD group only (by 7.7 mmHg vs. WKY FMT‐CD; P=0.06). Finally, chronic IP injection of butyrate in the SHR resulted in significant SBP increase compared to saline‐injected SHR (ΔSBP=14.5 mmHg, P<0.05).ConclusionSHR gut microbiota is pro‐hypertensive in the WKY. Moreover, subpressor Ang II exacerbates this hypertension in the presence of excess butyrate. Thus, elevated butyrate may interact with Ang II in the pathophysiology of hypertension, indicating the disadvantageous role of butyrate in the context of hypertension.Support or Funding Information1. American Heart Association 2. College of Veterinary Medicine, University of Florida

Butyrate increases IL-23 production by stimulated dendritic cells

The gut microbiota is essential for the maintenance of intestinal immune homeostasis and is responsible for breaking down dietary fiber into short-chain fatty acids (SCFAs). Butyrate, the most abundant bioactive SCFA in the gut, is a histone deacetylase inhibitor (HDACi), a class of drug that has potent immunomodulatory properties. This characteristic of butyrate, along with our previous discovery that conventional dendritic cells (DCs) are required for the development of experimental colitis, led us to speculate that butyrate may modulate DC function to regulate gut mucosal homeostasis. We found that butyrate, in addition to suppressing LPS-induced bone marrow-derived DC maturation and inhibiting DC IL-12 production, significantly induced IL-23 expression. The upregulation of mRNA subunit IL-23p19 at the pretranslational level was consistent with the role of HDACi on the epigenetic modification of gene expression. Furthermore, the mechanism of IL-23p19 upregulation was independent of Stat3 and ZBP89. Coculture of splenocytes with LPS-stimulated DCs pretreated with or without butyrate was performed and showed a significant induction of IL-17 and IL-10. We demonstrated further the effect of butyrate in vivo using dextran sulfate sodium (DSS)-induced colitis and found that the addition of butyrate in the drinking water of mice worsened DSS-colitis. This is in contrast to the daily intraperitoneal butyrate injection of DSS-treated mice, which mildly improved disease severity. Our study highlights a novel effect of butyrate in upregulating IL-23 production of activated DCs and demonstrates a difference in the host response to the oral vs. systemic route of butyrate administration.

The Nuclear Kinase Mitogen- and Stress-Activated Protein Kinase 1 Regulates Hippocampal Chromatin Remodeling in Memory Formation

The extracellular signal-regulated kinase (ERK)/MAPK (mitogen-activated protein kinase) cascade has been established as a potent regulator of gene transcription in long-term memory formation, but the precise mechanisms of this regulation are poorly understood. ERK does not directly affect many of its nuclear targets, but rather must act through intermediary kinases. In this study, we investigated the role of mitogen- and stress-activated protein kinase 1 (MSK1), a nuclear kinase downstream of ERK, in chromatin remodeling during hippocampus-dependent memory formation. Mice lacking MSK1 show impaired Pavlovian fear conditioning and spatial learning, as well as a deficiency in histone phosphorylation and acetylation in the hippocampus after fear training. In addition, hippocampal slices from MSK1 knock-out mice exhibit a deficiency in both histone phosphorylation and acetylation after activation of the ERK pathway in vitro. In vivo injections of a histone deacetylase inhibitor, sodium butyrate, fail to alleviate the fear conditioning deficit in MSK1 knock-out mice. Finally, MSK1 knock-out mice demonstrate a deficiency in cAMP response element-binding protein (CREB) phosphorylation after fear training, which persists after sodium butyrate injection. This suggests that CREB phosphorylation and histone acetylation represent parallel targets of MSK1 function. Our study identifies MSK1 as an important regulator of chromatin remodeling in long-term memory.

Butyrate reduces liver metastasis of rat colon carcinoma cells in vivo and resistance to oxidative stress in vitro

Injection of the rat colon carcinoma cell line CC531 into spleen of syngeneic rats results in considerable amounts of liver metastases within 14 days. We investigated whether preincubation of the cells with butyrate reduced their metastatic ability in vivo and whether this was accompanied by reduction in related properties such as secretion of metalloproteinases and their ability to withstand oxidative stress. Butyrate incubation reduced cell growth rate and initiated apoptosis in a dose- and time-related manner, but proliferation was retrieved when cultivation was continued in medium without butyrate. Splenic injection of butyrate treated, proliferating cells resulted in significantly reduced amounts of tumor mass compared to untreated cells. The butyrate treated cells were more susceptible to oxidative stress than control cells, as demonstrated by increased number of apoptotic cells and reduced cell growth after exposure to menadione. A reduction in cellular glutathione was found after prolonged incubation with butyrate. Butyrate appeared not to alter the secretion of active metalloproteinases from the cells although an apparent increase in proforms was demonstrated. Neither did butyrate alter the synthesis of metalloproteinase inhibitors. Lastly, a reduced adhesion of the tumor cells to collagen coated matrix was found after butyrate treatment. Thus, the inhibitory effects of butyrate on tumor malignancy are caused by a diversity of mechanisms.

Effects of Heat Exposure on Plasma Insulin, Glucagon and Metabolites in Response to Nutrient Injection in Heifers

Effects of heat exposure on plasma insulin, glucagon, and metabolite responses following injection of various nutrients were investigated in heifers. Four heifers, fed hay wafer and a commercial concentrate, were exposed to thermoneutral (20°C) and hot (30°C) environments. Glucose, arginine and butyrate (each injection at 0.625mmol/kg) and insulin (0.2U/kg) were injected intravenously, and then blood samples were collected at regular intervals through jugular vein catheters. Insulin secretion in response to glucose and arginine injection was not affected by heat exposure. However, the insulin response following butyrate injection was inhibited in heifers exposed to heat. In the hot environment, glucagon responses following the arginine and butyrate injections were augmented significantly, however glucagon levels were inhibited following the glucose injection. It is concluded that heat stress causes an inhibition of the insulin response to butyrate injection, and an increase in the glucagon response following arginine and butyrate injection. Plasma metabolite concentrations altered in accordance with the changes in the concentration of pancreatic hormones.

Effects of intravenous injection of butyrate, valerate and their isomers on endocrine pancreatic responses in conscious sheep ( Ovis aries)

1. 1. The effects of intravenous injection of n-butyrate, iso-butyrate, n-valerate and iso-valerate on insulin and glucagon secretion was examined in conscious sheep. 2. 2. Each sodium salt of the short chain fatty acids increased plasma insulin and glucagon concentrations in a dose-dependent manner (312–1250 μmol/kg body wt). 3. 3. Both butyrate and valerate isomers with branched carbon chains had larger insulin releasing activity than isomers with straight carbon chains. 4. 4. The glucagon responses to butyrate or valerate did not differ between the isomers with straight carbon chains and those with branched carbon chains. 5. 5. Our results suggest that the receptive mechanism to short chain fatty acids, which may involve the nervous system, differs between the A cell and the B cell in sheep in vivo.

Effects of intravenous injection of butyrate on the exocrine pancreatic secretion in guinea pigs

1. 1. The stimulus-secretion coupling in the pancreatic exocrine responses to i.v. injection of sodium butyrate was investigated in guinea pigs in vivo and in vitro. 2. 2. Intravenous single injection of sodium butyrate (12.5–100 μmol/100g body wt) caused an increase in fluid and amylase secretion in a dose-dependent manner. The responses evoked by sodium butyrate (100 μmol/100g body wt) were not affected by prior injection of atropine (0.14 μmol/100g body wt) or hexamethonium (4 μmol/100g body wt). 3. 3. The chloride concentration in secreted fluid increased slightly with an increase in flow rate in response to sodium butyrate, but decreased in response to secretin. 4. 4. The amylase release from the pancreatic segments evoked by sodium butyrate (10 −6–10 −2M) increased dose-dependently. The responses were potentiated in the presence of secretin (1 C.H.R.u./ml), but were suppressed in the presence of acetylcholine (10 −6 M) or in a Ca-free solution containing EGTA (10 −4 M). 5. 5. These results suggest that the secretory effects in response to i.v. injection of sodium butyrate probably arise from direct action on the acinar cells, and that an increase in cellular calcium concentration might be an important step in the secretion process, in guinea pig exocrine pancreas.

Effect of short-chain fatty acids on the secretory response of the ovine exocrine pancreas.

The secretory response of the exocrine pancreas to short-chain fatty acids has been studied in anesthetized sheep and in isolated lobules. Butyrate, propionate, and acetate stimulated pancreatic juice flow and protein and amylase output in the anesthetized sheep. The secretory response to butyrate was significantly greater than that of propionate or acetate. Rapid intravenous injection of butyrate (625 mumol/kg) caused a 13-fold rise in the juice flow, 26-fold in protein output, and 37-fold in amylase output above the basal levels within 5 min and declined to basal levels over a period of 30 min. Responses to butyrate (625 mumol/kg) were comparable with those obtained with 2 U/kg pancreozymin (Boots). Detectable responses were obtained with 15 mu/kg butyrate, 125 mumol/kg propionate, and 312.5 mumol/kg acetate. The secretory response to butyrate (625 mumol/kg) was not affected by pretreatment with atropine and hexamethonium. In the isolated lobule preparation, amylase release increased in response to butyrate in a concentration-dependent manner, reaching a maximal level at 1 mM and declining at 100 mM. It is concluded that short-chain fatty acids act directly on pancreatic acinar cells to stimulate secretion. The physiological implications of these findings are considered.

Effects of cold exposure on insulin and glucagon secretion in sheep.

The effectiveness of cold exposure on the secretion of insulin and glucagon were examined using five adult sheep. Endocrine responses were studied in a warm environment and after cold exposure (0 C) from 4-19 days. Compared to levels at room temperature, basal plasma glucose levels were elevated during cold exposure, but basal levels of plasma insulin and glucagon were unchanged. Cold exposure significantly decreased the early insulin response to a primed iv infusion of glucose. Plasma glucose and glucagon levels during glucose infusion were unaffected by cold exposure. The decrease in plasma glucose after iv insulin injection (0.2 U/kg BW) was greater during cold exposure than at room temperature. Butyrate injection (0.625 mmol/kg, iv) resulted in a significantly lower secretion of both insulin and glucagon in the cold than in the warm environment. The glucagon response to arginine infusion (0.5 g/kg over 30 min, iv) was elevated by cold exposure, whereas the insulin response to arginine tended to be reduced. Propranolol infusion (20 micrograms/kg . min, iv) caused a slight inhibition of insulin secretion in the cold environment, but did not affect glucagon levels in either the cold or warm environment. Phentolamine infusion (20 micrograms/kg . min, iv) inhibited glucagon secretion, particularly in the cold environment, and caused a markedly greater stimulation of insulin secretion in the cold. It is concluded that cold exposure insufficient to cause hypothermia decreases insulin secretion in response to a variety of stimuli. Effects of cold on glucagon secretion depend upon the stimulating agent used.

The development of ketogenesis at birth in the rat.

In the suckling newborn rat, blood ketone bodies begin to increase slowly 4h after birth and then rise sharply between 12 and 16h, whereas the major increase in plasma non-esterified fatty acids and liver carnitine occurs during the first 2h of life, parallel with the onset of suckling. In the starved newborn rat, which shows no increase in liver carnitine unless it is fed with a carnitine solution, the developmental pattern of the ketogenic capacity (tested by feeding a triacylglycerol emulsion, which increases plasma non-esterified fatty acids by 3-fold) is the same as in the suckling animal. This suggests that the increases in plasma non-esterified fatty acids and liver carnitine seen 2h after birth in the suckling animal are not the predominant factors inducing the switch-on of ketogenesis. Injection of butyrate to starved newborn pups resulted in a pattern of blood ketone bodies which was similar to that found after administration of triacylglycerols, but, at all time points studied, the hyperketonaemia was more pronounced with butyrate. It is suggested that, even if the entry of long-chain fatty acids into the mitochondria is a rate-limiting step, it is not the only factor controlling ketogenesis after birth in the rat. As in the adult rat, there is a reciprocal correlation between the liver glycogen content and the concentration of ketone bodies in the blood.

Fatty acid, epinephrine, and glucagon hyperglycemia in normal and depancreatized sheep.

ARTICLESFatty acid, epinephrine, and glucagon hyperglycemia in normal and depancreatized sheepRW Phillips, WA House, RA Miller, JL Mott, and DL SoobyRW Phillips, WA House, RA Miller, JL Mott, and DL SoobyPublished Online:01 Nov 1969https://doi.org/10.1152/ajplegacy.1969.217.5.1265MoreSectionsPDF (897 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByThe effect of length of storage and sodium benzoate on the nutritive value of reconstituted sorghum grain silages for dairy cowsJournal of Dairy Science, Vol. 102, No. 10Effects of benzoic acid and its analogues on insulin and glucagon secretion in sheepEuropean Journal of Pharmacology, Vol. 280, No. 2Acute Metabolic and Hormonal Effects of Intravenously Administered Sodium n-Butyrate in Untreated and Alloxan-Diabetic SheepJournal of Veterinary Medicine Series A, Vol. 40, No. 1-10Effects of intravenous injection of butyrate, valerate and their isomers on endocrine pancreatic responses in conscious sheep (Ovis aries)Comparative Biochemistry and Physiology Part A: Physiology, Vol. 95, No. 3Hormonal regulation of metabolism in ruminants; a reviewLivestock Production Science, Vol. 14, No. 4Effect of adrenergic drugs on glucose and plasma glucagon and insulin responses to xylazine in sheepResearch in Veterinary Science, Vol. 33, No. 1The Depressional Influence of Ammonia on the Level of Blood Amino Acids in Wethers and Bulls13 May 2010 | Zentralblatt für Veterinärmedizin Reihe A, Vol. 22, No. 6Studies on the control of gluconeogenesis in sheep: effect of propionate, casein and butyrate infusions24 July 2007 | British Journal of Nutrition, Vol. 29, No. 2Vormagenstoffwechsel und Glucogenese beim Wiederkäuer19 October 2009 | Zeitschrift für Tierphysiologie Tierernährung und Futtermittelkunde, Vol. 28, No. 1-5 More from this issue > Volume 217Issue 5November 1969Pages 1265-1268 Copyright & PermissionsCopyright © 1969 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1969.217.5.1265PubMed5346289History Published online 1 November 1969 Published in print 1 November 1969 Metrics

Differential effects of sodium butyrate and physostigmine upon the activities of para-sleep in acute brain stem preparations

The differential effects of sodium butyrate and physostigmine sulfate in inducing the pontine (NRPC) spike bursts and REM characteristic of PS were studied in cats with transections or lesions at different levels of the pons. The preparations were made by: (1) transection at the midpontine pretrigeminal level (MPT cat); (2) prepontine decerebration and transection between the pons and the medulla (IP preparation); and (3) prepontine decelebration (prepontine cat). The pontine-lesioned preparations were also made by bilateral electrolytic destructions of the rostroventral portions (RPL cat) or the caudodorsal portions (CPL cat) of the pons. The bursts of NRPC spikes and REM were induced by intravenous injection of physostigmine (0.05 mg/kg) and continued for 10–150 min (mean= 67 min; N = 69) in the MPT cat, for 17–120 min (mean= 44 min; N = 25) in the RPL cat and for 40–170 min (mean= 80 Min; N = 23) in the IP preparation. A similar phase of NRPC spike bursts with a duration of 7–73 min (mean= 26 min; N = 22) was induced by injection of butyrate (1.5m M/kg) in the IP preparation but not in the MPT and RPL cats. This effect of butyrate of physostigmine in inducing NRPC spike burst and REM was suppressed by injection of atropine sulfate (0.1 mg/kg) in the IP preparation. The electrical stimulation to NRPO suppressed the NRPC spikes during PS which appeared spontaneously or were induced by injection of physostigmine or butyrate in the prepontine cat. The mechanisms of induction of the activities characteristic of PS are discussed.

Pyruvate and Propionate Metabolism in Lactating Cows: EFFECT OF BUTYRATE ON PYRUVATE METABOLISM

The glucogenic behavior of butyrate in ruminants has been reported frequently, but the metabolic nature of this anomalous relationship has remained obscure. To test the possibility that the metabolism of butyrate affects gluconeogenesis, lactating cows were given intravenous injections of tracer amounts of pyruvate-2-14C and, in parallel experiments, of pyruvate-2-14C plus substrate amounts of sodium butyrate (0.7 mm per kg of body weight). When butyrate was injected, less 14C appeared in respired CO2 and more 14C in plasma glucose. The intramolecular labeling pattern in glutamate also changed with butyrate injection, with the result that more of the 14C was located in carbon derived from oxalacetate compared to carbon derived from acetyl-CoA. These results indicate that butyrate metabolism affects gluconeogenesis by sparing pyruvate oxidation, thereby conserving a glucogenic precursor, and, in addition, by enhancing the conversion of pyruvate to oxalacetate.