Project description:The effects of birth weight (BiW; low BiW [LBW] vs. high BiW [HBW]) and estimated breeding value (EBV) for protein deposition (low EBV [LBV] vs. high EBV [HBV]) on N retention, N efficiency, and concentrations of metabolites in plasma and urine related to N efficiency in growing pigs were studied. At an age of 14 wk, 10 LBW-LBV (BiW: 1.07 ± 0.09 [SD] kg; EBV: -2.52 ± 3.97 g/d, compared with an average crossbred pig with a protein deposition of 165 g/d), 10 LBW-HBV (BiW: 1.02 ± 0.13 kg; EBV: 10.47 ± 4.26 g/d), 10 HBW-LBV (BiW: 1.80 ± 0.13 kg; EBV: -2.15 ± 2.28 g/d), and 10 HBW-HBV (BiW: 1.80 ± 0.15 kg; EBV: 11.18 ± 3.68 g/d) male growing pigs were allotted to the experiment. The pigs were individually housed in metabolism cages and were subjected to an N balance study in two sequential periods of 5 d, after an 11-d dietary adaptation period. Pigs were assigned to a protein adequate (A) or protein restricted (R, 70% of A) regime in a change-over design. Pigs were fed 2.8 times the energy requirements for maintenance. Nontargeted metabolomics analyses were performed in urine and blood plasma samples. The N retention (in g/d) was higher in the HBW than in the LBW pigs (P < 0.001). The N retention (in g/[kg metabolic body weight (BW0.75) · d]) and N efficiency, however, were not affected by the BiW of the pigs. The N retention (P = 0.04) and N efficiency (P = 0.04) were higher in HBV than in LVB pigs on the A regime but were not affected by EBV in pigs on the R regime. Restricting the dietary protein supply with 30% decreased the N retention (P < 0.001) but increased the N efficiency (P = 0.003). Nontargeted metabolomics showed that a hexose, free amino acids (AA), and lysophosphatidylcholines were the most important metabolites in plasma for the discrimination between HBV and LBV pigs, whereas metabolites of microbial origin contributed to the discrimination between HBV and LBV pigs in urine. This study shows that BiW does not affect N efficiency in the later life of pigs. Nitrogen efficiency and N retention were higher in HBV than in LBV pigs on the A regime but similar in HBV and LBV pigs on the R regime. In precision feeding concepts aiming to further optimize protein and AA efficiency in pigs, the variation in EBV for protein deposition of pigs should be considered as a factor determining N retention, growth performance, and N efficiency.
Project description:Background/aimsFetal metabolism may be changed by the exposure to maternal factors, and the route to obesity may already set in utero. Cord blood metabolites might predict growth patterns and later obesity. We aimed to characterize associations of cord blood with birth weight, postnatal weight gain, and BMI in adolescence.MethodsOver 700 cord blood samples were collected from infants participating in the German birth cohort study LISAplus. Glycerophospholipid fatty acids (GPL-FA), polar lipids, non-esterified fatty acids (NEFA), and amino acids were analyzed with a targeted, liquid chromatography-tandem mass spectrometry based metabolomics platform. Cord blood metabolites were related to growth factors by linear regression models adjusted for confounding variables.ResultsCord blood metabolites were highly associated with birth weight. Lysophosphatidylcholines C16:1, C18:1, C20:3, C18:2, C20:4, C14:0, C16:0, C18:3, GPL-FA C20:3n-9, and GPL-FA C22:5n-6 were positively related to birth weight, while higher cord blood concentrations of NEFA C22:6, NEFA C20:5, GPL-FA C18:3n-3, and PCe C38:0 were associated with lower birth weight. Postnatal weight gain and BMI z-scores in adolescents were not significantly associated with cord blood metabolites after adjustment for multiple testing.ConclusionPotential long-term programming effects of the intrauterine environment and metabolism on later health cannot be predicted with profiling of the cord blood metabolome.
Project description:Exposure to cigarette smoke during development is linked to neurodevelopmental delays and cognitive impairment including impulsivity, attention deficit disorder, and lower IQ. However, brain region specific biomolecular alterations induced by developmental cigarette smoke exposure (CSE) remain largely unexplored. In the current molecular phenotyping study, a mouse model of 'active' developmental CSE (serum cotinine > 50 ng/mL) spanning pre-implantation through third trimester-equivalent brain development (gestational day (GD) 1 through postnatal day (PD) 21) was utilized. Hippocampus tissue collected at the time of cessation of exposure was processed for gel-based proteomic and non-targeted metabolomic profiling with partial least squares-discriminant analysis (PLS-DA) for selection of features of interest. Ingenuity pathway analysis was utilized to identify candidate molecular and metabolic pathways impacted within the hippocampus. CSE impacted glycolysis, oxidative phosphorylation, fatty acid metabolism, and neurodevelopment pathways within the developing hippocampus.
Project description:ObjectivesAdverse pregnancy outcomes are more common in women with SLE compared with healthy women, but we lack prognostic biomarkers. Plasma IFN-α protein levels are elevated in a subgroup of pregnant women with SLE, but whether this is associated with pregnancy outcomes is unknown. We investigated the relationship between IFN-α, adverse pregnancy outcomes and the presence of autoantibodies in SLE pregnancy.MethodsWe followed 76 women with SLE prospectively. Protein levels of IFN-α were quantified in plasma collected in the second and third trimester with single-molecule array. Positivity for ANA and aPL antibodies was assessed during late pregnancy with multiplexed bead assay. Clinical outcomes included the adverse pregnancy outcomes small for gestational age (SGA), preterm birth and preeclampsia.ResultsDuring SLE pregnancy, women with SGA infants compared with those without had higher levels of plasma IFN-α protein, and IFN-α positivity was associated with lower birth weight of the infant. Preterm birth was associated with autoantibodies against chromatin. IFN-α protein levels associated positively with autoantibodies against chromatin, Smith/RNP (SmRNP) and RNP, but negatively with aPL antibodies.ConclusionElevated IFN-α protein in plasma of women with SLE is a potential risk factor for lower birth weight of their infants. The association between IFN-α and lower birth weight warrants further investigation regarding the pathophysiological role of IFN-α during SLE pregnancy.
Project description:This study examined the effects of recurrent sleep restriction on the plasma metabolome of adults with familial risk of type 2 diabetes. Eleven healthy adults (6M/5F; mean [SD] age: 26 [3]years; BMI 23.5 [2.3]kg/m(2)) with parental history of type 2 diabetes participated in a two-condition, two-period randomized crossover study at the Clinical Resource Center at an academic hospital. Each participant completed two 8-night inpatient sessions with restricted (5.5-h time-in-bed) vs. adequate (8.5-h time-in-bed) sleep opportunity while daily food intake and physical activity were carefully controlled. A combination of two UHPLC/MS/MS platforms and one GC/MS platform was used to measure 362 biochemicals in fasting plasma samples collected from study participants the morning after each 8-night sleep treatment. Relative concentrations of 12 amino acids and related metabolites were increased when sleep was curtailed. Sleep restriction also induced elevations in several fatty acid, bile acid, steroid hormone, and tricarboxylic acid cycle intermediates. In contrast, circulating levels of glucose, some monosaccharides, gluconate, and five-carbon sugar alcohols tended to decline when sleep was reduced. Recurrent sleep curtailment affected multiple pathways of intermediary metabolism in adults at risk for type 2 diabetes. An elevation in plasma amino acids and related biochemicals was the most pronounced metabolic signature seen in response to 8 nights of sleep restriction.
Project description:Administration of pivalate has been demonstrated to be suitable for induction of secondary car-nitine deficiency (CD) in pigs, as model objects for humans. In order to comprehensively charac-terize the metabolic effects of secondary CD in the liver of pigs, the present study aimed to carry out comparative analysis of hepatic transcriptome and plasma metabolome of a total of 12, male 5-weeks-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, 13 me-tabolites were identified to be lower and 5 metabolites to be higher in group PIV than in group CON (p < 0.05). Despite pivalate-induced CD caused only weak alterations of the hepatic tran-scriptome and the plasma metabolome, the changes observed indicate that secondary CD modu-lates the innate immune response of pigs.
Project description:Low birth weight puppies present an increased risk of neonatal mortality, morbidity, and some long-term health issues. Yet it has not been investigated if those alterations could be linked to the gut microbiota composition and evolution. 57 puppies were weighed at birth and rectal swabs were performed at 5 time points from birth to 28 days of age. Puppies were grouped into three groups based on their birth weight: low birth weight (LBW), normal birth weight (NBW) and high birth weight (HBW). 16S rRNA gene sequencing was used to highlight differences in the fecal microbiota. During the first three weeks, the relative abundance of facultative anaerobic bacteria such as E. coli, C. perfringens and Tyzzerella was higher in LBW feces, but they catch back with the other groups afterwards. HBW puppies showed higher abundances of Faecalibacterium and Bacteroides during the neonatal period, suggesting an earlier maturation of their microbiota. The results of this study suggest that birth weight impact the initial establishment of the gut microbiota in puppies. Innovative strategies would be desired to deal with altered gut microbiota in low birth weight puppies aiming to improve their survival and long term health.
Project description:Feline obesity elicits a plethora of metabolic responses leading to comorbidities, with potential reversal during weight loss. The specific metabolic alterations and biomarkers of organ dysfunction are not entirely understood. Untargeted, high-throughput metabolomic technologies may allow the identification of biological components that change with weight status in cats, increasing our understanding of feline metabolism. The objective of this study was to utilize untargeted metabolomic techniques to identify biomarkers and gain mechanistic insight into the serum metabolite changes associated with reduced food intake and weight loss in overweight cats. During a four-wk baseline period, cats were fed to maintain body weight. For 18 wk following baseline, cats were fed to lose weight at a rate of ~1.5% body weight/wk. Blood serum metabolites were measured at wk 0, 1, 2, 4, 8, 12, and 16. A total of 535 named metabolites were identified, with up to 269 of them being altered (p- and q-values < 0.05) at any time point. A principal component analysis showed a continual shift in metabolite profile as weight loss progressed, with early changes being distinct from those over the long term. The majority of lipid metabolites decreased with weight loss; however, ketone bodies and small lipid particles increased with weight loss. The majority of carbohydrate metabolites decreased with weight loss. Protein metabolites had a variable result, with some increasing, but others decreasing with weight loss. Metabolic mediators of inflammation, oxidative stress, xenobiotics, and insulin resistance decreased with weight loss. In conclusion, global metabolomics identified biomarkers of reduced food intake and weight loss in cats, including decreased markers of inflammation and/or altered macronutrient metabolism.