Corrigendum: Oleaginous yeast Rhodotorula toruloides biomass effect on the metabolism of Arctic char (Salvelinus alpinus).

[This corrects the article DOI: 10.3389/fmolb.2022.931946.].

Oleaginous yeast Rhodotorula toruloides biomass effect on the metabolism of Arctic char (Salvelinus alpinus).

Sustainability issues arise when using fish oil and vegetable oils in fish feed production for aquaculture purposes. Microbial production of single cell oil is a potential alternative as a lipid ingredient in the production of fish feed. In this study, we replaced the vegetable oils with the oleaginous yeast R. toruloides biomass in the diet of Arctic char (S. alpinus) and investigated the effects on health and composition. Measurement of fish growth parameters showed a higher liver weight and hepatosomatic index in the experimental group of fish fed partly with yeast biomass compared to a control group fed a diet with vegetable oils. No significant differences in the lipid content of muscle and liver tissues were found. The fatty acid profiles in the muscle of both fish groups were similar while the experimental fish group had a higher amount of monounsaturated fatty acids in the liver. Histology of livers showed no significant difference in the number of lipid droplets. The size of hepatic lipid droplets seemed to be related to liver fat content. Quantification of metabolites in the liver revealed no differences between the fish groups while plasma metabolites involved in energy pathways such as alanine, 3-hydroxybutyrate, creatinine, serine, betaine, and choline were significantly higher in the experimental fish group.

Identification of prediagnostic metabolites associated with prostate cancer risk by untargeted mass spectrometry-based metabolomics: A case-control study nested in the Northern Sweden Health and Disease Study.

Prostate cancer (PCa) is the most common cancer form in males in many European and American countries, but there are still open questions regarding its etiology. Untargeted metabolomics can produce an unbiased global metabolic profile, with the opportunity for uncovering new plasma metabolites prospectively associated with risk of PCa, providing insights into disease etiology. We conducted a prospective untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics analysis using prediagnostic fasting plasma samples from 752 PCa case-control pairs nested within the Northern Sweden Health and Disease Study (NSHDS). The pairs were matched by age, BMI, and sample storage time. Discriminating features were identified by a combination of orthogonal projection to latent structures-effect projections (OPLS-EP) and Wilcoxon signed-rank tests. Their prospective associations with PCa risk were investigated by conditional logistic regression. Subgroup analyses based on stratification by disease aggressiveness and baseline age were also conducted. Various free fatty acids and phospholipids were positively associated with overall risk of PCa and in various stratification subgroups. Aromatic amino acids were positively associated with overall risk of PCa. Uric acid was positively, and glucose negatively, associated with risk of PCa in the older subgroup. This is the largest untargeted LC-MS based metabolomics study to date on plasma metabolites prospectively associated with risk of developing PCa. Different subgroups of disease aggressiveness and baseline age showed different associations with metabolites. The findings suggest that shifts in plasma concentrations of metabolites in lipid, aromatic amino acid, and glucose metabolism are associated with risk of developing PCa during the following two decades.

Serum metabolomics analysis reveals increased lipid catabolism in mildly hyperbilirubinemic Gilbert's syndrome individuals.

BACKGROUND: The protective role of mildly elevated bilirubin against CVD and diabetes mellitus type 2 (DMT2) is associated with a favorable lipid phenotype. As the mechanistic understanding of this protection in humans remains elusive, we aimed to assess the metabolomics profile of mildly hyperbilirubinemic (Gilbert's syndrome; GS) individuals especially targeting lipid catabolism. METHODS AND RESULTS: Using NMR serum metabolomics of 56 GS individuals and 56 age and gender-matched healthy controls, GS individuals demonstrated significantly greater concentrations of acetylcarnitine (+20%, p < 0.001) and the ketone bodies, 3-hydroxybutyric acid (+132%, p < 0.001), acetoacetic acid (+95%, p < 0.001) and acetone (+46%, p < 0.001). Metabolites associated with an increased mitochondrial lipid metabolism such as citrate (+15%, p < 0.001), anaplerotic amino acid intermediates and creatinine were significantly greater and creatine significantly reduced in GS individuals. Stimulators of lipid catabolism including AMPK (+59%, p < 0.001), pPPARα (+24%, p < 0.001) and T3 (+9%, p = 0.009) supported the metabolomics data while concomitantly blood glucose and insulin (-33%, p = 0.002) levels were significantly reduced. We further showed that the increased lipid catabolism partially mediates the favorable lipid phenotype (lower triglycerides) of GS individuals. Increased trimethylamine (+35%, p < 0.001) indicated changes in trimethylamine metabolism, an emerging predictor of metabolic health. CONCLUSION: We showed an enhanced lipid catabolism in mildly hyperbilirubinemic individuals, novel evidence as to why these individuals are leaner and protected against chronic metabolic diseases emphasizing bilirubin to be a promising future target in obese and dyslipidemia patients.

Improved Automated Quantification Algorithm (AQuA) and Its Application to NMR-Based Metabolomics of EDTA-Containing Plasma.

We have recently presented an Automated Quantification Algorithm (AQuA) and demonstrated its utility for rapid and accurate absolute metabolite quantification in 1H NMR spectra in which positions and line widths of signals were predicted from a constant metabolite spectral library. The AQuA quantifies based on one preselected signal per metabolite and employs library spectra to model interferences from other metabolite signals. However, for some types of spectra, the interspectral deviations of signal positions and line widths can be pronounced; hence, interferences cannot be modeled using a constant spectral library. We here address this issue and present an improved AQuA that handles interspectral deviations. The improved AQuA monitors and characterizes the appearance of specific signals in each spectrum and automatically adjusts the spectral library to model interferences accordingly. The performance of the improved AQuA was tested on a large data set from plasma samples collected using ethylenediaminetetraacetic acid (EDTA) as an anticoagulant (n = 772). These spectra provided a suitable test system for the improved AQuA since EDTA signals (i) vary in intensity, position, and line width between spectra and (ii) interfere with many signals from plasma metabolites targeted for quantification (n = 54). Without the improvement, ca. 20 out of the 54 metabolites would have been overestimated. This included acetylcarnitine and ornithine, which are considered particularly difficult to quantify with 1H NMR in EDTA-containing plasma. Furthermore, the improved AQuA performed rapidly (<10 s for all spectra). We believe that the improved AQuA provides a basis for automated quantification in other data sets where specific signals show interspectral deviations.

Metabolomics analysis reveals altered metabolites in lean compared with obese adolescents and additional metabolic shifts associated with hyperinsulinaemia and insulin resistance in obese adolescents: a cross-sectional study.

INTRODUCTION: Hyperinsulinaemia and insulin resistance (IR) are strongly associated with obesity and are forerunners of type 2 diabetes. Little is known about metabolic alterations separately associated with obesity, hyperinsulinaemia/IR and impaired glucose tolerance (IGT) in adolescents. OBJECTIVES: To identify metabolic alterations associated with obesity, hyperinsulinaemia/IR and hyperinsulinaemia/IR combined with IGT in obese adolescents. METHODS: 81 adolescents were stratified into four groups based on body mass index (lean vs. obese), insulin responses (normal insulin (NI) vs. high insulin (HI)) and glucose responses (normal glucose tolerance (NGT) vs. IGT) after an oral glucose tolerance test (OGTT). The groups comprised: (1) healthy lean with NI and NGT, (2) obese with NI and NGT, (3) obese with HI and NGT, and (4) obese with HI and IGT. Targeted nuclear magnetic resonance-based metabolomics analysis was performed on fasting and seven post-OGTT plasma samples, followed by univariate and multivariate statistical analyses. RESULTS: Two groups of metabolites were identified: (1) Metabolites associated with insulin response level: adolescents with HI (groups 3-4) had higher concentrations of branched-chain amino acids and tyrosine, and lower concentrations of serine, glycine, myo-inositol and dimethylsulfone, than adolescents with NI (groups 1-2). (2) Metabolites associated with obesity status: obese adolescents (groups 2-4) had higher concentrations of acetylcarnitine, alanine, pyruvate and glutamate, and lower concentrations of acetate, than lean adolescents (group 1). CONCLUSIONS: Obesity is associated with shifts in fat and energy metabolism. Hyperinsulinaemia/IR in obese adolescents is also associated with increased branched-chain and aromatic amino acids.

Thyroid and androgen receptor signaling are antagonized by µ-Crystallin in prostate cancer.

Androgen deprivation therapy (ADT) remains a key approach in the treatment of prostate cancer (PCa). However, PCa inevitably relapses and becomes ADT resistant. Besides androgens, there is evidence that thyroid hormone thyroxine (T4) and its active form 3,5,3'-triiodo-L-thyronine (T3) are involved in the progression of PCa. Epidemiologic evidences show a higher incidence of PCa in men with elevated thyroid hormone levels. The thyroid hormone binding protein µ-Crystallin (CRYM) mediates intracellular thyroid hormone action by sequestering T3 and blocks its binding to cognate receptors (TRα/TRß) in target tissues. We show in our study that low CRYM expression levels in PCa patients are associated with early biochemical recurrence and poor prognosis. Moreover, we found a disease stage-specific expression of CRYM in PCa. CRYM counteracted thyroid and androgen signaling and blocked intracellular choline uptake. CRYM inversely correlated with [18F]fluoromethylcholine (FMC) levels in positron emission tomography/magnetic resonance imaging of PCa patients. Our data suggest CRYM as a novel antagonist of T3- and androgen-mediated signaling in PCa. The role of CRYM could therefore be an essential control mechanism for the prevention of aggressive PCa growth.

Identification of metabolites associated with prostate cancer risk: a nested case-control study with long follow-up in the Northern Sweden Health and Disease Study.

BACKGROUND: Prostate cancer is the second most frequently diagnosed cancer in men. Metabolomics can potentially provide new insights into the aetiology of prostate cancer by identifying new metabolic risk factors. This study investigated the prospective association between plasma metabolite concentrations and prostate cancer risk, both overall and by stratifying for disease aggressiveness and baseline age. METHODS: In a case-control study nested in the Northern Sweden Health and Disease Study, pre-diagnostic concentrations of 148 plasma metabolites were determined using targeted mass spectrometry- and nuclear magnetic resonance-based metabolomics in 777 prostate cancer cases (follow-up ≥ 5 years) and 777 matched controls. Associations between prostate cancer risk and metabolite concentrations were investigated using conditional logistic regression conditioned on matching factors (body mass index, age and sample storage time). Corrections for multiple testing were performed using false discovery rate (20%) and Bonferroni. Metabolomics analyses generated new hypotheses, which were investigated by leveraging food frequency questionnaires (FFQs) and oral glucose tolerance tests performed at baseline. RESULTS: After correcting for multiple testing, two lysophosphatidylcholines (LPCs) were positively associated with risk of overall prostate cancer (all ages and in older subjects). The strongest association was for LPC C17:0 in older subjects (OR = 2.08; 95% CI 1.45-2.98; p < 0.0001, significant also after the Bonferroni correction). Observed associations with risk of overall prostate cancer in younger subjects were positive for glycine and inverse for pyruvate. For aggressive prostate cancer, there were positive associations with six glycerophospholipids (LPC C17:0, LPC C20:3, LPC C20:4, PC ae C38:3, PC ae C38:4 and PC ae C40:2), while there was an inverse association with acylcarnitine C18:2. Moreover, plasma LPC C17:0 concentrations positively correlated with estimated dietary intake of fatty acid C17:0 from the FFQs. The associations between glycerophospholipids and prostate cancer were stronger in case-controls with normal glucose tolerance. CONCLUSIONS: Several glycerophospholipids were positively associated with risk of overall and aggressive prostate cancer. The strongest association was observed for LPC C17:0. The associations between glycerophospholipids and prostate cancer risk were stronger in case-controls with normal glucose tolerance, suggesting a link between the glucose metabolism status and risk of prostate cancer.

Indication of metabolic inflexibility to food intake in spontaneously overweight Labrador Retriever dogs.

BACKGROUND: Obesity in dogs is an increasing problem associated with morbidity, shortened life span and poor life quality. Overweight dogs exhibit postprandial hyperlipidaemia, highlighting the need to identify potential dysregulations in lipid metabolism. This study investigated metabolites related to lipid metabolism (i.e. acylcarnitines and taurine) and phospholipids in a feed-challenge test and aimed to identify metabolic variations in spontaneously overweight dogs. Twenty-eight healthy male Labrador Retriever dogs were included, 12 of which were classified as lean (body condition score (BCS) 4-5 on a 9-point scale) and 16 as overweight (BCS 6-8). After overnight fasting (14-17 h), fasting blood samples were collected and dogs were fed a high-fat meal followed by postprandial blood sample collection hourly for 4 h. Liquid chromatography-time of flight mass spectrometry (LC-TOFMS) was used to identify plasma metabolites and phospholipids. Multivariate models, mixed model repeated measures and linear regression analyses were used for data interpretation. RESULTS: In all dogs, propionylcarnitine, stearoylcarnitine and nine phospholipids increased in response to food intake, while vaccenylcarnitine decreased (P ≤ 0.005 for all). Overall, carnitine and acetylcarnitine signal areas in the feed-challenge test were lower in overweight dogs (P ≤ 0.004). Notably, fasting plasma acetylcarnitine was lower in overweight dogs than in lean dogs (P = 0.001) and it did not change in response to feeding. The latter finding was in contrast to the decreased acetylcarnitine signal area found in lean dogs at one hour postprandially (P < 0.0001). One fasting phosphatidylcholine (PCaa C38:4) was higher in prominently overweight dogs (BCS > 6) than in lean dogs (P < 0.05). CONCLUSIONS: Plasma carnitine status was overall lower in spontaneously overweight dogs than in lean dogs in this cohort of healthy Labrador Retriever dogs, indicating a potential carnitine insufficiency in the overweight group. The acetylcarnitine response in overweight dogs indicated decreased fatty acid oxidation at fasting and metabolic inflexibility to food intake. Further studies on metabolic inflexibility and its potential role in the metabolism of overweight dogs are warranted.

Glucose Appearance Rate Rather than the Blood Glucose Concentrations Explains Differences in Postprandial Insulin Responses between Wholemeal Rye and Refined Wheat Breads-Results from A Cross-Over Meal Study.

SCOPE: Ingestion of rye bread leads to lower postprandial plasma insulin concentrations than wheat bread ingestion, but most often not too different glucose profiles. The mechanism behind this discrepancy is still largely unknown. This study investigates whether glucose kinetics may explain the observed discrepancy. METHODS AND RESULTS: Nine healthy men participated in a crossover study, eating 50 g of available carbohydrates as either refined wheat (WB) or traditional wholemeal rye bread (WMR) during d-[6,6-2 H2 ]glucose infusion. Labeled glucose enrichment is measured by an HPLC-TOF-MS method. The calculated rate of glucose appearance (RaE) is significantly lower after ingestion of WMR during the initial 15 min postprandial period. Additionally, the 0-90 min RaE area under the curve (AUC) is significantly lower after ingestion of WMR, as is plasma gastric inhibitory polypeptide (GIP) at 60 and 90 min. Postprandial glycemic responses do not differ between the breads. Postprandial insulin is lower after ingestion of WMR at 45 and 60 min, as is the 0-90 min AUC. CONCLUSION: Ingestion of WMR elicits a lower rate of glucose appearance into the bloodstream compared with WB. This may explain the lower insulin response observed after rye bread ingestion, commonly known as the rye factor.

Metabolomics analysis revealed metabolic changes in patients with diarrhea-predominant irritable bowel syndrome and metabolic responses to a synbiotic yogurt intervention.

PURPOSE: Irritable bowel syndrome is a gastrointestinal disorder which can influence human metabolism. It has been demonstrated that probiotics are beneficial in controlling IBS. Thus, the main objective of the present study was to determine metabolic changes in response to diarrhea predominant irritable bowel syndrome (IBS-D) and to investigate the metabolic effects of a synbiotic intervention on serum, urine, and stool samples from IBS-D patients and healthy controls using proton nuclear magnetic resonance (1HNMR). METHODS: A 1HNMR-based metabolomics study was conducted on urine and serum metabolites from 16 healthy and eight IBS-D participants at baseline and after 4 weeks of a synbiotic yogurt intervention. RESULTS: At the baseline, serum acetoacetate, myo-inositol, and sarcosine concentrations were higher and threonine and methionine concentrations were lower in the IBS-D cohort than the control group. Moreover, Indoxyl-sulfate concentration of urine was lower and dimethylamine and taurine were higher in the IBS-D group. After intervention, serum concentration of ketone bodies decreased, choline, phenylalanine, and branched-chain amino acids increased in IBS-D group. Metabolomics analysis indicated a shift in one-carbon metabolism. Thus, the level of serum homocysteine was determined and found to be higher in the IBS-D cohort at baseline, and then decreased after the intervention. CONCLUSION: IBS causes a shift in one-carbon metabolism and these changes can be reversed by a synbiotic intervention. An increase in the number of fecal Lactobacilli and an improvement in the health status of IBS-D patients were also observed in response to intervention.

Plasma metabolite profiles in healthy women differ after intervention with supplemental folic acid v. folate-rich foods.

Public health authorities recommend all fertile women to increase their folate intake to 400 µg/d by eating folate-rich foods or by taking a folic acid supplement to protect against neural tube defects. In a previous study it was shown that folate-rich foods improved folate blood status as effectively as folic acid supplementation. The aim of the present study was to investigate, using NMR metabolomics, the effects of an intervention with a synthetic folic acid supplement v. native food folate on the profile of plasma metabolites. Healthy women with normal folate status received, in parallel, 500 µg/d synthetic folic acid from a supplement (n 18), 250 µg/d folate from intervention foods (n 19), or no additional folate (0 µg/d) through a portion of apple juice (n 20). The metabolic profile of plasma was measured using 1H-NMR in fasted blood drawn at baseline and after 12 weeks of intervention. Metabolic differences between the groups at baseline and after intervention were assessed using a univariate statistical approach (P ≤ 0·001, Bonferroni-adjusted significance level). At baseline, the groups showed no significant differences in measured metabolite concentrations. After intervention, eight metabolites, of which six (glycine, choline, betaine, formate, histidine and threonine) are related to one-carbon metabolism, were identified as discriminative metabolites. The present study suggests that different folate forms (synthetic v. natural) may affect related one-carbon metabolites differently.

Impact of Reduced Dietary Levels of Eicosapentaenoic Acid and Docosahexaenoic Acid on the Composition of Skin Membrane Lipids in Atlantic Salmon ( Salmo salar L.).

Membrane lipids, including sphingolipids and glycerol-phospholipids, are essential in maintaining the skin's barrier function in mammals, but their composition in fish skin and their response to diets have not been evaluated. This study investigated the impacts of reducing dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on membrane lipids in the skin of Atlantic salmon through a 26 week feeding regime supplying different levels (0-2.0% of dry mass) of EPA/DHA. Ceramide, glucosylceramide, sphingomyelin, sphingosine, and sphinganine in salmon skin were analyzed for the first time. Higher concentrations of glucosylceramide and sphingomyelin and higher ratios of glucosylceramide/ceramide and sphingomyelin/ceramide were detected in the deficient group, indicating interruptions in sphingolipidomics. Changes in the glycerol-phospholipid profile in fish skin caused by reducing dietary EPA and DHA were observed. There were no dietary impacts on epidermal thickness and mucus-cell density, but the changes in the phospholipid profile suggest that low dietary EPA and DHA may interrupt the barrier function of fish skin.

The Effect of Lipopolysaccharide-Induced Experimental Bovine Mastitis on Clinical Parameters, Inflammatory Markers, and the Metabolome: A Kinetic Approach.

Mastitis is an inflammatory condition of the mammary tissue and represents a major problem for the dairy industry worldwide. The present study was undertaken to study how experimentally induced acute bovine mastitis affects inflammatory parameters and changes in the metabolome. To this end, we induced experimental mastitis in nine cows by intramammary infusion of 100 µg purified Escherichia coli lipopolysaccharide (LPS) followed by kinetic assessments of cytokine responses (by enzyme-linked immunosorbent assay), changes in the metabolome (assessed by nuclear magnetic resonance), clinical parameters (heat, local pain perception, redness, swelling, rectal temperature, clot formation, and color changes in the milk), and milk somatic cell counts, at several time points post LPS infusion. Intramammary LPS infusion induced clinical signs of mastitis, which started from 2 h post infusion and had returned to normal levels within 24-72 h. Milk changes were seen with a delay compared with the clinical signs and persisted for a longer time. In parallel, induction of IL-6 and TNF-α were seen in milk, and there was also a transient elevation of plasma IL-6 whereas plasma TNF-α was not significantly elevated. In addition, a robust increase in CCL2 was seen in the milk of LPS-infused cows, whereas G-CSF, CXCL1, and histamine in milk were unaffected. By using a metabolomics approach, a transient increase of plasma lactose was seen in LPS-induced cows. In plasma, significant reductions in ketone bodies (3-hydroxybutyrate and acetoacetate) and decreased levels of short-chain fatty acids, known to be major products released from the gut microbiota, were observed after LPS infusion; a profound reduction of plasma citrate was also seen. Intramammary LPS infusion also caused major changes in the milk metabolome, although with a delay in comparison with plasma, including a reduction of lactose. We conclude that the LPS-induced acute mastitis rapidly affects the plasma metabolome and cytokine induction with similar kinetics as the development of the clinical signs, whereas the corresponding effects in milk occurred with a delay.

AQuA: An Automated Quantification Algorithm for High-Throughput NMR-Based Metabolomics and Its Application in Human Plasma.

A key limiting step for high-throughput NMR-based metabolomics is the lack of rapid and accurate tools for absolute quantification of many metabolites. We developed, implemented, and evaluated an algorithm, AQuA (Automated Quantification Algorithm), for targeted metabolite quantification from complex 1H NMR spectra. AQuA operates based on spectral data extracted from a library consisting of one standard calibration spectrum for each metabolite. It uses one preselected NMR signal per metabolite for determining absolute concentrations and does so by effectively accounting for interferences caused by other metabolites. AQuA was implemented and evaluated using experimental NMR spectra from human plasma. The accuracy of AQuA was tested and confirmed in comparison with a manual spectral fitting approach using the ChenomX software, in which 61 out of 67 metabolites quantified in 30 human plasma spectra showed a goodness-of-fit (r2) close to or exceeding 0.9 between the two approaches. In addition, three quality indicators generated by AQuA, namely, occurrence, interference, and positional deviation, were studied. These quality indicators permit evaluation of the results each time the algorithm is operated. The efficiency was tested and confirmed by implementing AQuA for quantification of 67 metabolites in a large data set comprising 1342 experimental spectra from human plasma, in which the whole computation took less than 1 s.

Metabolomics Approach To Evaluate a Baltic Sea Sourced Diet for Cultured Arctic Char (Salvelinus alpinus L.).

Aqua feeds traditionally rely on fishmeal as a protein source, which is costly and unsustainable. A new feed was formulated in the study with Baltic Sea sourced decontaminated fishmeal, Mytilus edulis and Saccharomyces cerevisiae, and given to Arctic char (Salvelinus alpinus) for ten months. The diet-induced changes on metabolic profile in fish plasma, liver, and muscle were studied relative to a fishmeal-based standard diet by using a 1H NMR-based metabolomics approach. Fish fed the test diet had higher content of betaine and lower levels of trimethylamine-N-oxide and aromatic amino acids in plasma or tissues, which were mainly caused by the diet. The metabolomics results are useful to understand the mechanism of lower body mass, smaller Fulton's condition factor, and a tendency of less lipid content observed in fish fed the test diet. Thus, modifications on the dietary levels of these compounds in the feed are needed to achieve better growth performance.

Metabolic changes in serum metabolome in response to a meal.

PURPOSE: The change in serum metabolic response from fasting state to postprandial state provides novel insights into the impact of a single meal on human metabolism. Therefore, this study explored changes in serum metabolite profile after a single meal. METHODS: Nineteen healthy postmenopausal women with normal glucose tolerance participated in the study. They received a meal consisting of refined wheat bread (50 g carbohydrates, 9 g protein, 4.2 g fat and 2.7 g dietary fibre), 40 g cucumber and 300 mL noncaloric orange drink. Blood samples were collected at fasting and five postprandial time points. Metabolic profile was measured by nuclear magnetic resonance and targeted liquid chromatography-mass spectrometry. Changes over time were assessed with multivariate models and ANOVA, with baseline as control. RESULTS: The metabolomic analyses demonstrated alterations in phospholipids, amino acids and their breakdown products, glycolytic products, acylcarnitines and ketone bodies after a single meal. More specifically, phosphatidylcholines, lysophosphatidylcholines and citrate displayed an overall declining pattern, while leucine, isoleucine, methionine and succinate increased initially but declined thereafter. A sharp decline in acylcarnitines and ketone bodies and increase in glycolytic products postprandially suggest a switch in the body's energy source from ß-oxidation to glycolysis. Moreover, individuals with relatively high postprandial insulin responses generated a higher postprandial leucine responses compared to participants with lower insulin responses. CONCLUSIONS: The study demonstrated complex changes from catabolic to anabolic metabolism after a meal and indicated that the extent of postprandial responses is different between individuals with high and low insulin response.

Targeted metabolomics reveals differences in the extended postprandial plasma metabolome of healthy subjects after intake of whole-grain rye porridges versus refined wheat bread.

SCOPE: We previously found that whole-grain (WG) rye porridges suppressed appetite and improved glucose metabolism. This study aimed to investigate potential plasma metabolites that may be related to differences in those appetite and glucose responses. METHODS AND RESULTS: Twenty-one health subjects consumed six isocaloric breakfasts in a randomized cross-over study. Plain WG rye porridges (40 and 55 g), rye porridge enriched with different inulin: gluten proportions (9:3 g; 6:6 g; 3:9 g), and a 55 g refined wheat bread (control) were served as part of complete breakfast, followed by a standardized lunch. NMR metabolomics assessed 36 plasma metabolites and short chain fatty acids were measured by GC-MS from baseline up to 8 h. Pre-lunch plasma essential amino acids reflected protein composition and post-lunch plasma short chain fatty acids varied with fiber content in breakfasts. No correlations were observed between measured metabolites and glucose, insulin, or appetite responses. CONCLUSIONS: Differences in protein and fiber contents in breakfasts altered postprandial plasma amino acids and short chain fatty acids, respectively, but were unrelated to appetite and glucose responses. Further studies are warrant to identify the underlying mechanisms for the beneficial effects on appetite and second meal glucose responses after rye-based foods.

Non-targeted 1H-NMR-metabolomics suggest the induction of master regulators of energy metabolism in the liver of vitamin E-deficient rats.

The essential function of vitamin E in vivo is not fully understood. Several studies addressed changes in the pattern of gene expression induced by vitamin E, but often did not investigate if these changes altered biochemical pathways and are eventually translated into biological function. We therefore used (1)H-NMR metabolomics to investigate the biochemical effects in the liver of rats caused by long-term feeding with diets deficient (dVE; α-tocopherol (αT), <1; γ-tocopherol (γT), <1; all values in mg kg(-1) diet), marginal (mVE; αT, 6; γT, 11), sufficient (sVE; αT, 12; γT, 24), or fortified with vitamin E (fVE; αT, 140; γT, 24). The concentrations of four polar hepatic metabolites were affected by the vitamin E content of the diet; glucose was lower and creatine, phosphocholine, and betaine were higher in deficient compared with rats receiving vitamin E. To achieve further biochemical insight, we investigated transcriptional changes in genes involved in the regulation of metabolic pathways related to these metabolites. Transcription of PGC1α, PPARα, and PPARγ, transcription factors controlling energy metabolism, was lower and that of the fatty acid translocase CD36 higher in animals fed vitamin E-deficient compared to those fed vitamin E-replete diets. Our data thus indicate that consumption of a vitamin E-deficient diet may alter hepatic energy metabolism in rats.

Metabolomics reveals differences in postprandial responses to breads and fasting metabolic characteristics associated with postprandial insulin demand in postmenopausal women.

Changes in serum metabolic profile after the intake of different food products (e.g., bread) can provide insight into their interaction with human metabolism. Postprandial metabolic responses were compared after the intake of refined wheat (RWB), whole-meal rye (WRB), and refined rye (RRB) breads. In addition, associations between the metabolic profile in fasting serum and the postprandial concentration of insulin in response to different breads were investigated. Nineteen postmenopausal women with normal fasting glucose and normal glucose tolerance participated in a randomized, controlled, crossover meal study. The test breads, RWB (control), RRB, and WRB, providing 50 g of available carbohydrate, were each served as a single meal. The postprandial metabolic profile was measured using nuclear magnetic resonance and targeted LC-mass spectrometry and was compared between different breads using ANOVA and multivariate models. Eight amino acids had a significant treatment effect (P < 0.01) and a significant treatment × time effect (P < 0.05). RWB produced higher postprandial concentrations of leucine (geometric mean: 224; 95% CI: 196, 257) and isoleucine (mean ± SD: 111 ± 31.5) compared with RRB (geometric mean: 165; 95% CI: 147, 186; mean ± SD: 84.2 ± 22.9) and WRB (geometric mean: 190; 95% CI: 174, 207; mean ± SD: 95.8 ± 17.3) at 60 min respectively (P < 0.001). In addition, 2 metabolic subgroups were identified using multivariate models based on the association between fasting metabolic profile and the postprandial concentration of insulin. Women with higher fasting concentrations of leucine and isoleucine and lower fasting concentrations of sphingomyelins and phosphatidylcholines had higher insulin responses despite similar glucose concentration after all kinds of bread (cross-validated ANOVA, P = 0.048). High blood concentration of branched-chain amino acids, i.e., leucine and isoleucine, has been associated with the increased risk of diabetes, which suggests that additional consideration should be given to bread proteins in understanding the beneficial health effects of different kinds of breads. The present study suggests that the fasting metabolic profile can be used to characterize the postprandial insulin demand in individuals with normal glucose metabolism that can be used for establishing strategies for the stratification of individuals in personalized nutrition.