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Abstract Background Butyrate is known as histone deacetylase inhibitor, inducing histone hyperacetylation in vitro and playing a predominant role in the epigenetic regulation of gene expression and cell function. We hypothesized that butyrate, endogenously produced by intestinal microbial fermentation or applied as a nutritional supplement, might cause similar in vivo modifications in the chromatin structure of the hepatocytes, influencing the expression of certain genes and therefore modifying the activity of hepatic microsomal drug-metabolizing cytochrome P450 (CYP) enzymes. Methods An animal study was carried out in chicken as a model to investigate the molecular mechanisms of butyrate’s epigenetic actions in the liver. Broiler chicks in the early post-hatch period were treated once daily with orally administered bolus of butyrate following overnight starvation with two different doses (0.25 or 1.25 g/kg body weight per day) for five days. After slaughtering, cell nucleus and microsomal fractions were separated by differential centrifugation from the livers. Histones were isolated from cell nuclei and acetylation of hepatic core histones was screened by western blotting. The activity of CYP2H and CYP3A37, enzymes involved in biotransformation in chicken, was detected by aminopyrine N-demethylation and aniline-hydroxylation assays from the microsomal suspensions. Results Orally added butyrate, applied in bolus, had a remarkable impact on nucleosome structure of hepatocytes: independently of the dose, butyrate caused hyperacetylation of histone H2A, but no changes were monitored in the acetylation state of H2B. Intensive hyperacetylation of H3 was induced by the higher administered dose, while the lower dose tended to increase acetylation ratio of H4. In spite of the observed modification in histone acetylation, no significant changes were observed in the hepatic microsomal CYP2H and CYP3A37 activity. Conclusion Orally added butyrate in bolus could cause in vivo hyperacetylation of the hepatic core histones, providing modifications in the epigenetic regulation of cell function. However, these changes did not result in alteration of drug-metabolizing hepatic CYP2H and CYP3A37 enzymes, so there might be no relevant pharmacoepigenetic influences of oral application of butyrate under physiological conditions.

Lipopolysaccharides (LPS) challenge the metabolic integrity of high-yielding dairy cows, activating the immune system and altering energy metabolism. Fatty acid oxidation, a major energy-gaining pathway, can be improved by supplementary carnitine, facilitating the transport of fatty acids into mitochondria. The metabolic response to the LPS challenge could alter both the plasma and the milk metabolome. Plasma and milk samples collected from cows treated with (n = 27) or without (n = 27) dietary carnitine, before and after intravenous administration of LPS, were subjected to a targeted metabolomics analysis. Multivariate statistical analyses revealed that both plasma and milk metabolome changed in response to the LPS challenge in both the carnitine-supplemented and the control cows. Short-chain acylcarnitines (carbon chain length C2, C3, C4, and C5) and longchain acylcarnitines (C14, C16, and C18) had the highest performance to indicate LPS response when testing the predictive power of single metabolites using receiver-operator characteristics (ROC) analysis. The maximum area under a ROC curve (AUC) was 0.93. Biogenic amines, including sarcosine, and amino acids such as glutamine and isoleucine had AUC>0.80 indicating metabolic changes due to the LPS challenge. In summary, the metabolites involved in the LPS response were acylcarnitines C2 and C5, sarcosine, glutamine, and isoleucine in plasma, and acylcarnitines C4 and C5 in milk. The interrelationship of plasma and milk metabolome included correlation of acylcarnitines C2, C4, and C5 between plasma and milk. [ABSTRACT FROM AUTHOR]

Abstract Background Increasing evidence suggests that diets high in polyunsaturated fatty acids (PUFA) confer health benefits by improving insulin sensitivity and lipid metabolism in liver, muscle and adipose tissue. Methods The present study investigates metabolic responses in two different lines of mice either selected for high body weight (DU6) leading to rapid obesity development, or selected for high treadmill performance (DUhTP) leading to a lean phenotype. At 29 days of age the mice were fed standard chow (7.2% fat, 25.7% protein), or a high-fat diet rich in n-3 PUFA (n-3 HFD, 27.7% fat, 19% protein) or a high-fat diet rich in n-6 PUFA (n-6 HFD, 27.7% fat, 18.6% protein) for 8 weeks. The aim of the study was to determine the effect of these PUFA-rich high-fat diets on the fatty acid profile and on the protein expression of key components of insulin signalling pathways. Results Plasma concentrations of leptin and insulin were higher in DU6 in comparison with DUhTP mice. The high-fat diets stimulated a strong increase in leptin levels and body fat only in DU6 mice. Muscle and liver fatty acid composition were clearly changed by dietary lipid composition. In both lines of mice n-3 HFD feeding significantly reduced the hepatic insulin receptor β protein concentration which may explain decreased insulin action in liver. In contrast, protein kinase C ζ expression increased strongly in abdominal fat of n-3 HFD fed DUhTP mice, indicating enhanced insulin sensitivity in adipose tissue. Conclusions A diet high in n-3 PUFA may facilitate a shift from fuel deposition in liver to fuel storage as fat in adipose tissue in mice. Tissue specific changes in insulin sensitivity may describe, at least in part, the health improving properties of dietary n-3 PUFA. However, important genotype-diet interactions may explain why such diets have little effect in some population groups.

Background: Little is known about the implications of hyperinsulinemia on energy metabolism, and such knowledge might help understand the pathophysiology of insulin dysregulation. Objectives: Describe differences in the metabolic response to an oral glucose test, depending on the magnitude of the insulin response. Animals Twelve Icelandic horses in various metabolic states. Methods: Horses were subjected to 3 oral glucose tests (OGT; 0.5 g/kg body weight glucose). Basal, 120 and 180 minutes samples were analyzed using a combined liquid chromatography tandem mass spectrometry and flow injection analysis tandem mass spectrometry metabolomic assay. Insulin concentrations were measured using an ELISA. Analysis was performed using linear models and partial least‐squares regression. Results: The kynurenine : tryptophan ratio increased over time during the OGT (adjusted P‐value =.001). A high insulin response was associated with lower arginine (adjusted P‐value =.02) and carnitine (adjusted P‐value =.03) concentrations. A predictive model using only baseline samples performed well with as few as 7 distinct metabolites (sensitivity, 86%; 95% confidence interval [CI], 81%‐90%; specificity, 88%; 95% CI, 84%‐92%). Conclusions and Clinical Importance: Our results suggest induction of low‐grade inflammation during the OGT. Plasma arginine and carnitine concentrations were lower in horses with high insulin response and could constitute potential therapeutic targets. Development of screening tools to identify insulin‐dysregulated horses using only baseline blood sample appears promising. [ABSTRACT FROM AUTHOR]

Different diagnostic tests to determine the insulin sensitivity in horses are commonly used in veterinary practice. However, endocrine and metabolic responses provoked by physiological processes during the respective test procedures are not well described. In the present study, oral glucose tests (OGTs) and combined iv glucose insulin tests (CGITs) were employed under standardized conditions. The OGTs and CGITs were performed in twelve healthy warmblood horses of different sex, age (15±6.5 years), weight (567±81kg) and body condition score (4.8±1.6). Horses were tested under fasting conditions. The OGT was performed with 1g/kgBW glucose administered via nasogastric intubation and CGIT was performed by injection of 150mg/kg BW glucose solution and 0.1IU/kgBW porcine zinc-insulin. Blood samples were taken for three hours at intervals of 15 minutes and were analysed for insulin, glucose, triglyceride, non-esterified fatty acids (NEFA), fructosamine and cortisol concentrations. Glucose concentrations increased in the OGTs and CGITs directly after administration. Insulin concentrations increased significantly in OGTs within 30 minutes and stayed elevated for three hours. Peak concentrations of 493.98±86.84μIU/mL were measured in the CGITs, followed by a continuous decline. Baseline NEFA concentrations varied between individual horses and declined in a comparable manner to similar minimum concentrations of 93.82±53.22μmol/L in OGTs and 91.97±56.89μmol/L in CGITs. Regarding the stress response of the test procedure, cortisol concentrations remained unaffected during CGITs, while the OGT procedure was accompanied by a significant initial rise in cortisol concentrations. To conclude, OGT and CGIT mirror different facets of the metabolic response to a glycemic stimulus, highlighting different aspects of glucose homeostasis and insulin regulation. During the CGIT, insulin dynamics with porcine zinc-insulin differ from insulin dynamics described in reports published previously using short-acting insulins. Furthermore, the antilipolytic effects of insulin during OGTs and CGITs via endogenous secretion or exogenous injection resulted in similar reduction of NEFA concentrations and unaffected triglyceride concentrations. This indicates a saturation of the suppression of lipolysis by insulin with already low concentrations and no induction of re-esterification in liver tissue. [ABSTRACT FROM AUTHOR]

: NSAIDs are commonly used in colic therapy. Especially in the post-operative stage, dysmotility is a severe complication. Literature provides evidence of an effect on the contractility of the gastrointestinal tract through NSAIDs. Therefore, the aim of this study was to investigate the effects of NSAIDs on the equine small intestine and, in particular, to accurately examine the effects on the injured intestine. Included were horses with a healthy intestine which had been subject to a median laparotomy with two consecutive experimental ischemias and reperfusions. In the first experiment, an in vitro application of the NSAIDs flunixin and firocoxib was carried out. In the second experiment, the respective NSAID was administered to the probands in vivo and the samples were examined by means of a measurement of the contractility in vitro. The in vitro application of the non-selective COX inhibitor flunixin had significant inhibitory effects on the contractility of the equine jejunum in vitro. These inhibitory effects occurred in comparison to all other samples. In vitro application of firocoxib had no significant effects on the contractility in vitro but showed a slight insignificant increasing effect, especially on the frequency of contractions of the circular musculature. After intravenous in vivo application, subsequent sample taking and examination, the results of the measurements of contractility in vitro were clearly more heterogenous. This, for example, led to a significant increase in frequency of contractions of the longitudinal musculature of the samples, damaged by ischemia and reperfusion, after intravenous application of flunixin, and to a significantly higher amplitude of contractions of the longitudinal musculature of the samples, damaged by ischemia and reperfusion, after intravenous application of firocoxib. These inconsistent effects and the deviations to the effects after in vitro application probably indicate a toxicological effect after in vitro application of the agents and an altered initial situation in the second experiment due to a panenteric occurrence (resulting from previous damage through the first experiment). The explanation would be an overdosage and, therefore, an intoxication of the tissue after in vitro application of the agents because the inhibitory effects of flunixin only occurred in high concentrations. Based on the examinations of the current study, significant differences between the in vitro application of flunixin and firocoxib on the in vitro contractility of the equine jejunum could be determined. The inhibitory effects of flunixin were dependent on its concentration and only appeared in high concentrations (2.7×10-5M). Although the dosages applied in vitro, were oriented towards plasma concentrations of the agents after intravenous application or concentrations used in other studies, it was not clear whether these concentrations corresponded to the actually reached tissue concentrations after intravenous or oral application of the agents. Due to high plasma protein bindings, the actual tissue concentration after intravenous or oral application could be much lower. In the current study, also merely the in vitro contractility was examined and conclusions regarding in vivo motility could not be drawn absolutely. The clinical relevance of the inhibitory effect of flunixin on the contractility in vitro after in vitro application cannot be estimated due to the current study. Also it is not clear to which extent the type of application (in vitro application and intravenous in vivo application) actually had an influence on the results. In the future, studies have to follow that examine the effects of selective and non-selective NSAIDs on the contractility and motility of the equine intestine after intra [ABSTRACT FROM AUTHOR]

Studies on the yolk and albumen content in bird eggs, and the effects of variations in their relative loads in the phenotype of the birds, have revealed multiple consequences at different levels of biological organization, from biochemical traits to behavior. However, little is known about the effect of albumen variation on energetics performance during development and early ontogeny, despite the fact that variation in energy expenditure may have consequences in terms of fitness for both feral and domestic species. In this work, we evaluated experimentally whether variations in the content of albumen of Gallus gallus eggs could generate differences in metabolic rates during embryonic development. Additionally, we assessed changes in the activity of mitochondrial enzymes (cytochrome c oxidase and citrate synthase) in skeletal muscles and liver. Finally, we evaluated the success of hatching of these embryos and their metabolic rates (MR) post-hatching. The results revealed a significant reduction in MR in the last fifth of embryonic life, and reduced catabolic activities in the skeletal muscle of chicks hatched from albumen-removed eggs. However, the same group demonstrated an increase in catabolic activity in the liver, suggesting the existence of changes in energy allocation between tissues. Besides, we found a decrease in hatching success in the albumen-removed group, suggesting a negative effect of the lower albumen content on eggs, possibly due to lower catabolic activities in skeletal muscle. We also found a compensatory phenomenon in the first week after hatching, i.e., birds from albumen-removed eggs did not show a decrease in MR either at thermoneutral temperatures or at 10°C, compared to the control group. Collectively, our data suggest that a reduction in albumen may generate a trade-off between tissue metabolic activities, and may explain the differences in metabolic rates and hatching success, supporting the immediate adaptive response (IAR) hypothesis. [ABSTRACT FROM AUTHOR]

In ruminant feeding, the reduction of dietary protein is an effective approach for decreasing the excretion of N. In non-ruminant species, the intestinal absorption of Ca was affected when dietary protein was reduced. Therefore, it was the aim of the present study to characterise the intestinal absorption of Ca and inorganic phosphate (Pi) in goats fed different N and Ca diets. Intestinal flux rates of Ca and Pi were determined in goats fed a reduced N and Ca diet by Ussing chamber experiments. For a more mechanistic approach, the uptake of Ca and Pi in intestinal brush-border membrane vesicles (BBMV), the expression levels of the epithelial Ca channel transient receptor potential vanilloid channel type 6 (TRPV6), the sodium-dependent Pi transporter (NaPi) IIb and the vitamin D receptor (VDR) were measured. In goats fed a reduced N and Ca diet, the intestinal flux rates of Ca and Pi were elevated. However, the reduced N and Ca diet had no effect on the uptake of Ca and Pi in intestinal BBMV, while the expression of TRPV6 and NaPi IIb protein in the corresponding intestinal segments was even decreased. The mRNA expression of NaPi IIb and VDR was not affected. Therefore, a post-transcriptional regulation of TRPV6 and NaPi IIb protein was suggested in goats fed a reduced N and Ca diet. From these data, it can be concluded that the intestinal absorption of Ca and Pi in growing goats was affected by changes in dietary N and Ca intake like those in single-stomached animals but differently modulated. [ABSTRACT FROM AUTHOR]

Presents information on a study which examined the influence of dietary phosphorus depletion on central pathways of intermediary metabolism in rats. Methodology of the study; Results and discussion.