scholarly journals Limited Impact of Pivalate-Induced Secondary Carnitine Deficiency on Hepatic Transcriptome and Hepatic and Plasma Metabolome in Nursery Pigs

Metabolites ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 573
Author(s):  
Robert Ringseis ◽  
Sarah M. Grundmann ◽  
Sven Schuchardt ◽  
Erika Most ◽  
Klaus Eder
Keyword(s):  
Hepatic Metabolism ◽  
Carnitine Deficiency ◽  
Innate Immune ◽  
Metabolic Effects ◽  
Vehicle Group ◽  
Plasma Metabolites ◽  
P Value ◽  
Nursery Pigs ◽  
Plasma Metabolome ◽  
Hepatic Transcriptome

Administration of pivalate has been demonstrated to be suitable for the induction of secondary carnitine deficiency (CD) in pigs, as model objects for humans. In order to comprehensively characterize the metabolic effects of secondary CD in the liver of pigs, the present study aimed to carry out comparative analysis of the hepatic transcriptome and hepatic and plasma metabolome of a total of 12 male 5-week-old pigs administered either pivalate (group PIV, n = 6) or vehicle (group CON, n = 6) for 28 days. Pigs of group PIV had approximately 40–60% lower concentrations of free carnitine and acetylcarnitine in plasma, liver and different skeletal muscles than pigs of group CON (p < 0.05). Transcript profiling of the liver revealed 140 differentially expressed genes (DEGs) between group PIV and group CON (fold change > 1.2 or <−1.2, p-value < 0.05). Biological process terms dealing with the innate immune response were found to be enriched with the DEGs (p < 0.05). Using a targeted metabolomics approach for the simultaneous quantification of 630 metabolites, 9 liver metabolites and 18 plasma metabolites were identified to be different between group PIV and group CON (p < 0.05). Considering the limited alterations of the hepatic transcriptome and of the liver and plasma metabolome, it can be concluded that pivalate-induced secondary CD is not associated with significant hepatic metabolism changes in pigs.

scholarly journals 1143 METABOLIC EFFECTS OF TREATMENT OF SYSTEMIC CARNITINE DEFICIENCY

1981 ◽  
Vol 15 ◽  
pp. 633-633 ◽  
Author(s):  
Douglas Kerr ◽  
Susan Shurin ◽  
Kou-Yi Tserng ◽  
Charles Hoppel
Keyword(s):  
Carnitine Deficiency ◽  
Metabolic Effects ◽  
Systemic Carnitine Deficiency

scholarly journals Early Metabolic Benefits of Switching Hydrocortisone to Modified Release Hydrocortisone in Adult Adrenal Insufficiency

2021 ◽  
Vol 12 ◽  
Author(s):  
Christopher A. M. Bannon ◽  
Daniel Border ◽  
Petra Hanson ◽  
John Hattersley ◽  
Martin O. Weickert ◽  
...  
Keyword(s):  
Body Composition ◽  
Energy Expenditure ◽  
Adrenal Insufficiency ◽  
Fat Mass ◽  
Research Unit ◽  
Metabolic Effects ◽  
P Value ◽  
Modified Release ◽  
University Hospitals ◽  
Fat Percentage

PurposeTo compare metabolic effects of modified release hydrocortisone (MR-HC) with standard hydrocortisone (HC) therapies in adults with Adrenal Insufficiency (AI).MethodsAdult patients (n = 12) with AI, established on HC therapy, were recruited from Endocrinology clinics at University Hospitals Coventry and Warwickshire (UHCW), UK. Baseline (HC) metabolic assessments included fasting serum HbA1C, lipid and thyroid profiles, accurate measures of body composition (BodPod), and 24-h continuous measures of energy expenditure including Sleeping Metabolic Rate (SMR) using indirect calorimetry within the Human Metabolism Research Unit, UHCW. All participants then switched HC to MR-HC with repeat (MR-HC) metabolic assessments at 3 months. Paired-sample t-tests were used for data comparisons between HC and MR-HC assessments: P-value &lt;0.05 was considered significant.ResultsFollowing exclusion of 2 participants, analyses were based on 10 participants. Compared with baseline HC data, following 3 months of MR-HC therapy mean fat mass reduced significantly by −3.2 kg (95% CI: −6.0 to −0.4). Mean (SD) baseline HC fat mass vs repeat MR-HC fat mass: 31.9 kg (15.2) vs 28.7 kg (12.8) respectively, P = 0.03. Mean SMR increased significantly by +77 kcal/24 h (95% CI: 10–146). Mean (SD) baseline HC SMR vs repeat MR-HC SMR: 1,517 kcal/24 h (301) vs 1,594 kcal/24 h (344) respectively, P = 0.03. Mean body fat percentage reduced significantly by −3.4% (95% CI: −6.5 to −0.2). Other measures of body composition, energy expenditure, and biochemical analytes were equivalent between HC and MR-HC assessments.ConclusionsIn adults with AI, switching from standard HC to MR-HC associates with early metabolic benefits of reduced fat mass and increased SMR.

scholarly journals Microbiome and Metabolome Analyses Reveal Novel Interplay Between the Skin Microbiota and Plasma Metabolites in Psoriasis

2021 ◽  
Vol 12 ◽  
Author(s):  
Dongmei Chen ◽  
Jingquan He ◽  
Jinping Li ◽  
Qian Zou ◽  
Jiawei Si ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Metabolic Pathways ◽  
Pathogenic Bacteria ◽  
Plasma Metabolites ◽  
Skin Microbiome ◽  
Inflammatory Skin Disease ◽  
Skin Microbiota ◽  
Plasma Metabolome ◽  
Pathological Mechanism ◽  
New Evidence

Psoriasis is a chronic inflammatory skin disease that affects millions of people worldwide. There is still no effective approach for the clinical treatment of psoriasis. This is largely due to the lack of understanding of the pathological mechanism. Here, we comprehensively characterized the skin microbiome and plasma metabolome alterations of psoriasis patients. We observed that some pathogenic bacteria, including Vibrio, were significantly increased in psoriasis patients. The metabolomics results showed alterations in some metabolic pathways, especially pathways for lipid metabolism. In addition, microbiome-specific metabolites, including bile acids and kynurenine, were significantly changed. Correlation analysis revealed the interplay between the skin microbiota and plasma metabolites, especially between Vibrio and several lipids. Our results provide new evidence for the interplay between the skin microbiome and plasma metabolites, which is dramatically disrupted in psoriasis patients. This study also revealed the mechanism underlying the pathogenesis of psoriasis.

scholarly journals Effects of guar gum and cellulose on glucose absorption, hormonal release and hepatic metabolism in the pig

1992 ◽  
Vol 68 (3) ◽  
pp. 693-700 ◽  
Author(s):  
C. Simões Nunes ◽  
K. Malmlöf
Keyword(s):  
Portal Vein ◽  
Guar Gum ◽  
Latin Square ◽  
Glucagon Secretion ◽  
Hepatic Metabolism ◽  
Gastric Inhibitory Polypeptide ◽  
Hepatic Uptake ◽  
Metabolic Effects ◽  
Adaptation Period ◽  
Large White

Six Large White pigs (mean body-weight 59 (se 1.7) kg) were surgically fitted with permanent catheters in the portal vein, the brachiocephalic artery and the right hepatic vein, as well as with electromagnetic flow probes around the portal vein and the hepatic artery, and allowed to recover. The non-anaesthetized animals were given a basal non-fibre diet (diet A) alone or together with 60 g guar gum/kg (diet B) or 150 g purified cellulose/kg (diet C) by substitution for mica. The diets were given for weekly periods and according to a replicated 3x3 Latin square design. On the last day of each such adaptation period, test meals of 800 g were given before blood sampling. Sampling was continued for 8 h. Guar gum strongly reduced glucose apparent absorption without changing the absorption and the hepatic uptake profiles. Production rates of insulin, gastric inhibitory polypeptide and insulin-like growth factor-1 (IGF-1) were lowest after guar gum ingestion. However, the reductions in peripheral blood insulin levels caused by guar gum were not associated with a change in hepatic insulin extraction. IGF-1 appeared to be strongly secreted by the gut, whereas the liver had a net uptake of the peptide. Ingestion of guar gum increased the hepatic extraction coefficient of gut-produced IGF-1. Guar gum ingestion appeared also to decrease glucagon secretion.Cellulose at the level consumed had very few effects on the variables considered.It is suggested that the modulation of intestinal mechanisms by guar gum was sufficient to mediate the metabolic effects described

scholarly journals 208 Do prediction equations with high R-squared in low sample size studies have high predictive ability?

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 71-71
Author(s):  
Nick Serão ◽  
Amy Petry
Keyword(s):  
Rank Correlation ◽  
Predictive Ability ◽  
Prediction Equation ◽  
Small Sample ◽  
P Value ◽  
Prediction Equations ◽  
Nursery Pigs ◽  
Linear Effect ◽  
Randomized Design ◽  
Small Sample Sizes

Abstract The use of R-squared as a measurement of prediction in regression is a common practice in animal nutrition studies. Generally, studies use data used to estimate the prediction equation to calculate the R-squared of the equation, which does not represent prediction. The objective was to evaluate the predictive ability of prediction equations using independent datasets. Data were simulated in based on previously reported prediction equations for ADG in nursery pigs: 152 + 195(SID_Lysine%). A completely randomized design with SID_Lysine% levels of 1.2, 1.3, and 1.4% was used. Data were simulated for three CVs representing low, moderate, and high variation in ADG, for low number of replicates per treatment (RepTreat; 4 to 10, every 2). Data were simulated and analyses performed 300 times for each scenario. Prediction equations were estimated for each scenario when significant effect of SID_Lysine% was followed by a significant orthogonal contrast testing the linear effect of SID_Lysine% (P-value&lt; 0.05), and their R-squared were calculated (R2_training). The prediction equation was used to test the fit of the other datasets, and their R-squared were calculated and averaged for each prediction equation (R2_prediction). The relationship between R2_training and R2_prediction was assessed through Spearmen’s correlation and regression of R2_prediction on R2_training, across scenarios. The R2_training and R2_prediction averages were similar with 94.5% and 93.9%, 66.0% and 63.5%, and 46.1% and 42.7%, for low, moderate, and high CVs, respectively. The rank-correlation between R2_training and R2_prediction increased with CV: 0.23, 0.67, and 0.77, for low, moderate, and high CV, respectively. From regression analysis of R2_prediction on R2_training, as CV increased bias increased, with prediction equations with greater R2_training overestimating R2_prediction, and prediction equations with lower R2_training underestimating R2_prediction. These results indicate that in small sample sizes (≤10 per treatment), as CV increases, models with high R-squared are overestimated, and are not as predictable.

scholarly journals Plasma Metabolome Signature Indicative of BRCA1 Germline Status Independent of Cancer Incidence

2021 ◽  
Vol 11 ◽  
Author(s):  
Judith Penkert ◽  
Andre Märtens ◽  
Martin Seifert ◽  
Bernd Auber ◽  
Katja Derlin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Incidence ◽  
Cancer Predisposition ◽  
Metabolic Reprogramming ◽  
Metabolic Effects ◽  
Tissue Integrity ◽  
Breast Cancer Predisposition ◽  
Plasma Metabolome ◽  
Predisposition Genes ◽  
Unknown Structure

Individuals carrying a pathogenic germline variant in the breast cancer predisposition gene BRCA1 (gBRCA1+) are prone to developing breast cancer. Apart from its well-known role in DNA repair, BRCA1 has been shown to powerfully impact cellular metabolism. While, in general, metabolic reprogramming was named a hallmark of cancer, disrupted metabolism has also been suggested to drive cancer cell evolution and malignant transformation by critically altering microenvironmental tissue integrity. Systemic metabolic effects induced by germline variants in cancer predisposition genes have been demonstrated before. Whether or not systemic metabolic alterations exist in gBRCA1+ individuals independent of cancer incidence has not been investigated yet. We therefore profiled the plasma metabolome of 72 gBRCA1+ women and 72 age-matched female controls, none of whom (carriers and non-carriers) had a prior cancer diagnosis and all of whom were cancer-free during the follow-up period. We detected one single metabolite, pyruvate, and two metabolite ratios involving pyruvate, lactate, and a metabolite of yet unknown structure, significantly altered between the two cohorts. A machine learning signature of metabolite ratios was able to correctly distinguish between gBRCA1+ and controls in ~82%. The results of this study point to innate systemic metabolic differences in gBRCA1+ women independent of cancer incidence and raise the question as to whether or not constitutional alterations in energy metabolism may be involved in the etiology of BRCA1-associated breast cancer.

scholarly journals Effect of Fecal Microbiota Transplantation Combined With Mediterranean Diet on Insulin Sensitivity in Subjects With Metabolic Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Annefleur M. Koopen ◽  
Eduardo L. Almeida ◽  
Ilias Attaye ◽  
Julia J. Witjes ◽  
Elena Rampanelli ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Mediterranean Diet ◽  
Fecal Microbiota Transplantation ◽  
Synergistic Effects ◽  
Bacterial Species ◽  
Fecal Microbiota ◽  
Metabolic Effects ◽  
Plasma Metabolites ◽  
Beneficial Effects

BackgroundRecent studies demonstrate that a Mediterranean diet has beneficial metabolic effects in metabolic syndrome subjects. Since we have shown that fecal microbiota transplantation (FMT) from lean donors exerts beneficial effects on insulin sensitivity, in the present trial, we investigated the potential synergistic effects on insulin sensitivity of combining a Mediterranean diet with donor FMT in subjects with metabolic syndrome.DesignTwenty-four male subjects with metabolic syndrome were put on a Mediterranean diet and after a 2-week run-in phase, the subjects were randomized to either lean donor (n = 12) or autologous (n = 12) FMT. Changes in the gut microbiota composition and bacterial strain engraftment after the 2-week dietary regimens and 6 weeks post-FMT were the primary endpoints. The secondary objectives were changes in glucose fluxes (both hepatic and peripheral insulin sensitivity), postprandial plasma incretin (GLP-1) levels, subcutaneous adipose tissue inflammation, and plasma metabolites.ResultsConsumption of the Mediterranean diet resulted in a reduction in body weight, HOMA-IR, and lipid levels. However, no large synergistic effects of combining the diet with lean donor FMT were seen on the gut microbiota diversity after 6 weeks. Although we did observe changes in specific bacterial species and plasma metabolites, no significant beneficial effects on glucose fluxes, postprandial incretins, or subcutaneous adipose tissue inflammation were detected.ConclusionsIn this small pilot randomized controlled trial, no synergistic beneficial metabolic effects of combining a Mediterranean diet with lean donor FMT on glucose metabolism were achieved. However, we observed engraftment of specific bacterial species. Future trials are warranted to test the combination of other microbial interventions and diets in metabolic syndrome.

scholarly journals Effect of Testosterone Enanthate Modeling of Polycystic Ovary on Liver Irs-2 mRNA Expression in Rats: A Brief Report

2021 ◽  
Vol 18 (3) ◽  
pp. 0480
Author(s):  
Seyyed Amir Yasin Ahmadi ◽  
Mandana Beigi Boroujeni ◽  
Naser Pajouhi ◽  
Amin Hasanvand ◽  
Afshin Hasanvand ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Animal Models ◽  
Mrna Expression ◽  
Polycystic Ovary ◽  
Vehicle Group ◽  
Control Group ◽  
P Value ◽  
Free Access ◽  
Testosterone Enanthate ◽  
Significant Difference

There are many animal models for polycystic ovary (PCO); using exogenous testosterone enanthate is one of the methods of induction of these models. However, induction of insulin resistance should also be studied in the modeling technics. Therefore, the present study aims to investigate the expression of insulin receptor substrate (Irs)-2 mRNA in the liver tissue of rat PCO model. Nineteen Wistar rats were divided into three groups; (1) PCO modeling group (N =7) received daily 1.0 mg/100g testosterone enanthate solved in olive oil along with free access dextrose water 5%, (2) vehicle group (N =6), which handled like the PCO group, but did not receive testosterone enanthate, (3) control group (N =6) with standard care. All the animals were administered via intra-peritoneal injection for 14 days. Expression of Irs-2 mRNA was studied with real-time PCR and fold changes (FC) were reported. The average of expression in the control group was considered as the calibrator. About 13.4% expression reduction was found in the PCO group (FC =0.874, P-value =0.043). No significant reduction was found in the vehicle group (FC =0.951, P-value =0.076). However, analysis of variance did not show a significant difference between all the groups of study (P-value =0.085). The present model of PCO might induce insulin resistance at liver level with a low effect size via reduction in the mRNA expression of Irs-2. Study of the involved genes and molecules in other tissues of PCO animal models is suggested.

scholarly journals An integrated metagenomics and metabolomics approach implicates the microbiome-gut-brain-axis in the pathogenesis of Huntington’s disease transgenic mice

2020 ◽  
Author(s):  
Geraldine Kong ◽  
Susan Ellul ◽  
Vinod Narayana ◽  
Komal Kanojia ◽  
Harvey Tran Thai Ha ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Short Chain Fatty Acid ◽  
Neurodegenerative Disorder ◽  
Chain Fatty Acid ◽  
Short Chain ◽  
Plasma Metabolites ◽  
Gut Dysbiosis ◽  
Plasma Metabolome

Abstract Background: Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder with onset and severity of symptoms influenced by various environmental factors. Recent discoveries have highlighted the importance of the gastrointestinal microbiome in mediating the bidirectional communication between the central and enteric nervous system via circulating factors. Using shotgun sequencing, we investigated the gut microbiome composition in the R6/1 transgenic mouse model of HD from 4 to 12 weeks of age (early adolescent through to adult stages). Targeted metabolomics was also performed on the blood plasma of these mice (n=9 per group) at 12 weeks of age to investigate potential effects of gut dysbiosis on the plasma metabolome profile. The short-chain fatty acid (SCFA) concentrations in the plasma were validated using LCMS. Results: Beta diversity differed between HD mice compared to their WT littermates at 12 weeks of age, suggesting that gut dysbiosis occurs prior to overt motor symptoms. Modelled time profiles of each species, KEGG Orthologs and bacterial genes, revealed heightened volatility in the HD mice, indicating potential early effects of HD mutation in the gut prior to significant cognitive and motor dysfunction. In addition to gut dysbiosis at 12 weeks of age, we also found functional differences between the WT and HD mice. The butanoate metabolism pathway, which leads to the production of the protective short-chain fatty acid, butyrate, was increased in the gut. However, the plasma concentration of butyrate and propionate were both decreased in the HD mice, as determined by the SCFA validation. The concentrations of ATP were increased by over 4-fold in the HD plasma, which was contrary to expectations. The statistical integration of the metagenomics and metabolomics unraveled several Bacteroides species that were positively correlated with butyrate levels, and negatively correlated with ATP and pipecolic acid in the plasma. Blautia producta and Prevotella scopos were found to be negatively correlated with the butyrate and ATP respectively. Conclusions: Our study has revealed a previously unknown relationship between the gut bacteria and plasma metabolome, suggesting the potential role of gut in modulating the pathogenesis of HD via specific altered plasma metabolites which mediate gut-brain signalling.

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