Serum Metabolic Changes Research Articles

Studies on metabolic alterations due to hypobaric hypoxia in serum using NMR spectroscopy

Introduction The main physiological challenge in high altitude environment is hypoxia which affects the aerobic metabolism reducing the energy supply. These changes may further progress towards extreme environment related diseases. Rarely has the high-altitude biology been studied using system sciences and omics high-throughput technologies. Objective In the present study, 1H-NMR-based metabolomics, along with multivariate analysis, were employed in a preclinical rat model to characterise the serum metabolic changes under chronic hypobaric hypoxia (HH) stress. Material and methods Rats were exposed to simulated hypobaric hypoxia equivalent of 6700 m above the sea level. The serum samples were collected from control and HH-exposure (7, 14, and 21 days) of hypobaric hypoxia. Results and discussion The 1H-NMR metabolomics of the serum showed alterations in the metabolism of membranes, amino-acids altered cellular bioenergetics and osmoregulation. Multivariate statistical analysis revealed alterations in acetoacetate, choline, glutamine, acetate, betaine, ketone bodies and branched amino acid metabolites. Conclusion Present findings establishes the fingerprint biomarkers for chronic environmental hypoxia which will help in understanding extreme environment related health problems, early detection and developing strategies to clinically address high altitude hypoxia.

Perturbations in cardiac metabolism in a human model of acute myocardial ischaemia

IntroductionAcute myocardial ischaemia and the transition from reversible to irreversible myocardial injury are associated with abnormal metabolic patterns. Advances in metabolomics have extended our capabilities to define these metabolic perturbations on a metabolome-wide scale.ObjectivesThis study was designed to identify cardiac metabolic changes in serum during the first 5 min following early myocardial ischaemia in humans, applying an untargeted metabolomics approach.MethodsPeripheral venous samples were collected from 46 patients in a discovery study (DS) and a validation study (VS) (25 for DS, 21 for VS). Coronary sinus venous samples were collected from 7 patients (4 for DS, 3 for VS). Acute myocardial ischaemia was induced by transient coronary occlusion during percutaneous coronary intervention (PCI). Plasma samples were collected at baseline (prior to PCI) and at 1 and 5 min post-coronary occlusion. Samples were analyzed by Ultra Performance Liquid Chromatography-Mass Spectrometry in an untargeted metabolomics approach.ResultsThe study observed changes in the circulating levels of metabolites at 1 and 5 min following transient coronary ischaemia. Both DS and VS identified 54 and 55 metabolites as significant (P < 0.05) when compared to baseline levels, respectively. Fatty acid beta-oxidation and anaerobic respiration, lysoglycerophospholipids, arachidonic acid, docosahexaenoic acid, tryptophan metabolism and sphingosine-1-phosphate were identified as mechanistically important.ConclusionUsing an untargeted metabolomics approach, the study identified important cardiac metabolic changes in peripheral and coronary sinus plasma, in a human model of controlled acute myocardial ischaemia. Distinct classes of metabolites were shown to be involved in the rapid cardiac response to ischemia and provide insights into diagnostic and interventional targets.

A Metabolic Profiling Study of Realgar-Induced Acute Kidney Injury in Mice.

Realgar has been used as a type of mineral drug that contains arsenic for thousands of years. Previous studies have shown that Realgar-induced acute kidney injury is associated with abnormal metabolism, but the underlying mechanism is poorly understood. The aim of this study is to investigate the metabolic changes in serum and kidney tissues of mice exposed to Realgar by using a metabolomic approach and explore the molecular mechanisms of acute kidney injury induced by Realgar. Forty mice were randomly divided into four groups: Control group, 0.5-, 1.0, and 2.0 g/kg Realgar group. After 1 week, the body weight and kidney weight of the mice were measured. The serum and kidney samples were used for LC-MS spectroscopic metabolic profiling. Principal component analysis (PCA), correlation analysis, and pathway analysis were used to detect the nephrotoxic effects of Realgar. Body weight decreased significantly in the 2.0 g/kg group, and the kidney weight index also showed a dose-dependent increase in Realgar. The PCA score plot showed the serum and kidney tissue metabolic profile of mice exposed to 2.0 g/kg Realgar separated from the control group, while the lower-doses of 0.5 g/kg and 1.0 g/kg Realgar shown a similar view to the Control group. Thirty-three metabolites and seventeen metabolites were screened and identified in the serum and kidney of mice in a dose-dependent manner. respectively. Correlation analysis showed a strong correlation among these metabolites. Amino acid metabolism, lipid metabolism, glutathione metabolism, and purine metabolism pathways were found to be mainly associated with Realgar nephrotoxicity. This work illustrated the metabolic alterations in Realgar-induced nephrotoxic mice through a metabolomic approach.

Untargeted metabolomic approach to study the serum metabolites in women with polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS) is not only a kind of common endocrine syndrome but also a metabolic disorder, which harms the reproductive system and the whole body metabolism of the PCOS patients worldwide. In this study, we aimed to investigate the differences in serum metabolic profiles of the patients with PCOS compared to the healthy controls.Material and methods31 PCOS patients and 31 matched healthy female controls were recruited in this study, the clinical characteristics data were recorded, the laboratory biochemical data were detected. Then, we utilized the metabolomics approach by UPLC-HRMS technology to study the serum metabolic changes between PCOS and controls.ResultsThe metabolomics analysis showed that there were 68 downregulated and 78 upregulated metabolites in PCOS patients serum compared to those in the controls. These metabolites mainly belong to triacylglycerols, glycerophosphocholines, acylcarnitines, diacylglycerols, peptides, amino acids, glycerophosphoethanolamines and fatty acid. Pathway analysis showed that these metabolites were enriched in pathways including glycerophospholipid metabolism, fatty acid degradation, fatty acid biosynthesis, ether lipid metabolism, etc. Diagnosis value assessed by ROC analysis showed that the changed metabolites, including Leu–Ala/Ile–Ala, 3-(4-Hydroxyphenyl) propionic acid, Ile–Val/Leu–Val, Gly–Val/Val–Gly, aspartic acid, DG(34:2)_DG(16:0/18:2), DG(34:1)_DG(16:0/18:1), Phe–Trp, DG(36:1)_DG(18:0/18:1), Leu–Leu/Leu–Ile, had higher AUC values, indicated a significant role in PCOS.ConclusionThe present study characterized the difference of serum metabolites and related pathway profiles in PCOS patients, this finding hopes to provide potential metabolic markers for the prognosis and diagnosis of this disease.

Bupi Yishen formula attenuates kidney injury in 5/6 nephrectomized rats via the tryptophan-kynurenic acid-aryl hydrocarbon receptor pathway

BackgroundBupi Yishen Formula (BYF), a patent traditional Chinese medicine (TCM) formulation, has been used in the clinical treatment of chronic kidney disease (CKD). However, the mechanism of action of BYF has not been fully elucidated.MethodTo investigate the variation in the metabolic profile in response to BYF treatment in a rat model of 5/6 nephrectomy (Nx), rats in the treatment groups received low- or high-dose BYF. At the end of the study, serum and kidney samples were collected for biochemical, pathological, and western blotting analysis. Metabolic changes in serum were analyzed by liquid chromatography-tandem mass spectrometry.ResultsThe results showed that BYF treatment could reduce kidney injury, inhibit inflammation and improve renal function in a dose-dependent manner. In total, 405 and 195 metabolites were identified in negative and positive ion modes, respectively. Metabolic pathway enrichment analysis of differential metabolites based on the Kyoto Encyclopedia of Genes and Genomes database identified 35 metabolic pathways, 3 of which were related to tryptophan metabolism. High-dose BYF reduced the level of kynurenic acid (KA) by more than 50%, while increasing melatonin 25-fold and indole-3-acetic acid twofold. Expression levels of aryl hydrocarbon receptor (AhR), Cyp1A1, and CyP1B1 were significantly reduced in the kidney tissue of rats with high-dose BYF, compared to 5/6 Nx rats.ConclusionBYF has a reno-protective effect against 5/6 Nx-induced CKD, which may be mediated via inhibition of the tryptophan-KA-AhR pathway.

Long-term environmental cadmium exposure induced serum metabolic changes related to renal and liver dysfunctions in a female cohort from Southwest China

Cadmium (Cd), a toxic heavy mental, has been reported to be correlated with increased incidences of multiple diseases. Only a few studies have paid attention to screen the urine metabolites related to long-term environmental Cd exposure in humans. Research on the Cd exposure-related serum metabolic alternations and biological mechanisms linking Cd exposure to adverse health risks in humans is scanty. In this study, we investigated the serum Cd exposure-related metabolic alternations in a cohort of 101 non-smoking females (two polluted groups and one control group) and 18 Cd exposure-related metabolites were identified. A total of 16 clinical indicators of renal and hepatic functions and bone health were measured. Five health effect biomarkers including serum creatinine, alkaline phosphatase, total bilirubin, direct bilirubin and albumin to globulin ratio that are related to impaired renal and hepatic functions showed significant differences among the three groups and had close correlations with Cd levels. We identified intermediate metabolites that were associated with both Cd exposure and health effect biomarkers using a “meet-in-the-middle” approach. Fourteen Cd exposure-related metabolites in the metabolism of glycerophospholipids, sphingolipids, arachidic acid, linoleic acid and amino acids, were identified to be the intermediates of Cd exposure and the health effect biomarkers. Our findings provided evidence for the linkage of long-term environmental Cd exposure and the renal and hepatic insufficiency.

Integration of FGF21 Signaling and Metabolomics in High-Fat Diet-Induced Obesity.

Sex differences in obesity have been well established, but the metabolic mechanism underlying these differences remains unclear. In the present study, we determined the expression levels of endogenous fibroblast growth factor 21 (FGF21) and its related receptors in male and female mice that were fed a high-fat diet (HFD) for 12 weeks. We also analyzed the metabolic changes in serum and livers using a nuclear magnetic resonance-based metabolomics approach. Reverse transcription polymerase chain reaction and western blotting results revealed that the levels of FGFR1, FGFR2, and co-factor β-klotho were upregulated in female mice to alleviate FGF21 resistance induced by HFD. The metabolomics results demonstrated that the serum and liver metabolic patterns of HFD-fed male mice were significantly separated from those of the female HFD-fed group and the normal diet group. Furthermore, low-density lipoprotein/very low density lipoprotein and betaine levels were associated with the resistance of exogenous HFD in female mice. These findings imply that sex-based differences in metabolism and susceptibility to obesity might be mediated by the FGF21 signaling pathway.

Enteromorpha prolifera polysaccharide prevents high- fat diet-induced obesity in hamsters: A NMR-based metabolomic evaluation.

Enteromorpha prolifera polysaccharide (EP) has been shown to exhibit hypolipidemic and hypoglycemic activities in various experimental models. Here, an 1 H-NMR-based metabolomic study was conducted to explore the regulatory effects of EP on serum metabolic changes in obese hamsters. High-fat diet (HFD)-fed hamsters were orally administrated with EP (300, 450, or 600mg/kg) once daily for 12weeks. Compared with HFD-fed hamsters, EP treatment (450 and 600mg/kg) significantly decreased the body weight (by 8.69 and 8.24%), liver weight (by 7.87 and 8.25%), epididymal white adipose tissue (by 19.54 and 17.26%), perirenal white adipose tissue (by 28.09 and 28.94%), serum total cholesterol (by 24.31 and 18.61%), triglyceride (by 30.64 and 31.38%), and low-density lipoprotein cholesterol (by 38.26 and 36.30%), respectively. In addition, EP intervention also significantly decreased hepatic cholesterol (by 23.20, 38.16, and 34.57%) and triglyceride content (by 17.78, 41.47, and 35.50%) as well as serum levels of alanine aminotransferase (ALT) and ALT/aspartate aminotransferase (AST) ratio. The serum samples of normal diet (ND) group, HFD group and HFD + EP 450mg/kg (HFD+MEP) group were further analyzed by 1 H-NMR spectroscopy. Compared with ND group, 17 and 2 metabolites were significantly upregulated and downregulated in HFD group, respectively. Interestingly, EP treatment significantly downregulated nine metabolites and upregulated one metabolite when compared to those in HFD group. Our results indicated that EP intervention partially ameliorated HFD-induced metabolic dysfunction, and the most prominent metabolic pathways included citrate cycle, synthesis and degradation of ketone bodies, pyruvate metabolism, valine, leucine and isoleucine degradation, and arginine biosynthesis. PRACTICAL APPLICATION: Enteromorpha prolifera polysaccharide (EP), the main active component of Enteromorpha prolifera, is reported to have many biological activities. However, the antiobesity effect of EP and its corresponding metabolic mechanism have not been reported so far. The results of this study confirmed the antiobesity effect of EP on HFD-induced obese hamsters and elucidated its possible metabolic mechanism. Our study highlighted that EP might be used in weight-loss functional foods.

Analysis of serum metabolome of workers occupationally exposed to hexavalent chromium: A preliminary study

Hexavalent chromium (Cr(VI)) compound is considered as a common environmental and occupational pollutant due to widespread application in industry and agriculture. Cr(VI) as a carcinogen poses a serious threat to human health and the underlying mechanisms need further investigation. Previous studies had demonstrated the characteristic expression profiling after Cr(VI) treatment in vitro and in vivo at the levels of gene and protein. The comprehensive metabolic signatures were also conducive to discover potential biomarkers for effects assessment of Cr(VI) toxicity. In the current study, Ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) non-targeted metabolomics was applied to analyze serum metabolic changes in 77 chromate exposure workers and 62 controls. Thirteen metabolites were found significantly decreased and 41 metabolites were increased, which were involved in arginine and proline metabolism, and glycerophospholipid metabolism by bioinformatic analysis. Furthermore, there were significant negative correlations between blood Cr level and Arginine, PC(18:2/24:4) and PC(14:0/16:0), subgroup analyses indicated that these correlations were observed in male-only subgroups, and were not found among chromate workers and controls separately. Diet could be a potential confounder which was not controlled rigorously in this study. These findings provided preliminary clues to investigate the underlying mechanisms of Cr(VI)-induced toxicity and were required to be further verified in future researches.

High-Throughput Untargeted Serum Metabolomics Analysis of Hyperuricemia Patients by UPLC-Q-TOF/MS.

Hyperuricemia (HUA) as a metabolic disease is closely associated with metabolic disorders. The etiology and pathogenesis of HUA are not fully understood, so there is no radical cure so far. Metabolomics, a specialized study of endogenous small molecule substances, has become a powerful tool for metabolic pathway analysis of selected differential metabolites, which is helpful for initially revealing possible development mechanisms of various human diseases. Twenty HUA patients and 20 healthy individuals participated in the experiment, and ultrahigh performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) was employed to investigate serum samples to find differential metabolites. The statistical techniques used were principal component analysis and orthogonal partial least-squares discriminant analysis. The differences in metabolomics results of samples after pretreatment with different solvents were compared, 38, 20, 26, 28, 33, 50, and 40 potential differential metabolites were found, respectively, in HUA patient samples, and each group involved different metabolic pathways. Repetitive metabolites were removed, 138 differential metabolites in HUA serum were integrated for analysis, and the human body was affected by 7 metabolic pathways of glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, linoleic acid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and α-linolenic acid metabolism. In this work, the metabolomics approach based on UPLC-Q-TOF/MS was employed to investigate serum metabolic changes in HUA patients, 138 potential differential metabolites related to HUA were identified, which provided associations of lipids, amino acids, fatty acids, organic acids, and nucleosides profiles of HUA individuals. Metabolic pathways involved in glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, linoleic acid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and a-linolenic acid metabolism shed light on the understanding of the etiology and pathogenesis process of HUA.

Effect of Therapeutic Hypothermia on Physiologic, Histologic and Metabolomic Markers of Lung Injury in Experimental Acute Respiratory Distress Syndrome

Background Acute respiratory distress syndrome (ARDS) is a severe lung injury characterized by noncardiogenic pulmonary edema and rapid hypoxic respiratory failure. Therapeutic hypothermia improves outcomes of traumatic brain injury and cardiac injuries; however, it has not been widely used or studied in ARDS. Hypothermia may be helpful in reducing injury and inflammation associated with ARDS by reducing pro-inflammatory molecule production. Objective To evaluate the effect of therapeutic hypothermia on the development of injury and inflammation in experimental, short-term ARDS. Hypothesis Hypothermia induced at the onset of lung injury would mitigate histological and serum metabolic changes, as well as changes in respiratory elastance (E) and resistance (R). Methods The Animal Research Committee of the University of British Columbia approved all experimental procedures. Twenty female Yorkshire pigs were divided into 4 groups (n= 5 per group): normothermic control (C), normothermic injured (I), hypothermic control (HC), and hypothermic injured (HI). ARDS was induced via intrapulmonary injection of oleic acid. Hypothermia was induced with a cooling catheter placed into the left jugular vein. The normothermic groups had core temperatures maintained at 36.5-38°C and the hypothermic groups were cooled to 32°C. Animals were euthanized after a 12-hour follow-up period. Respiratory mechanical variables were quantified based the measurements of flow, airway pressure, and esophageal pressure. Tissue samples from the right diaphragmatic lobe were collected after euthanasia and examined for injury score. Plasma samples were collected and 1H-NMR spectroscopy analysis was performed to determine metabolite concentration. Results Therapeutic hypothermia reduced injury in the HI vs. I group (injury score= 0.51±0.18 vs. 0.76±0.06; p<0.05). All cohorts expressed distinct phenotypes with the HI cohort having a reduction in inflammatory metabolites (i.e., succinate) compared to the I cohort. Changes to respiratory mechanics were due to changes in lung E and R (ΔE from pre-injury= 45.55±14.17 cmH2O·l-1; ΔR from pre-injury= 3.07±1.99 cmH2O·l-1·s-1, p<0.05) and not chest-wall E and R (ΔE from pre-injury= 0.73±1.59 cmH2·l-1; ΔR from pre-injury= 0.59±0.14 cmH2O·l-1s-1, p>0.05), with trends for the HI group to have a lower lung R (p=0.99) and E (p=0.93) compared to the I group. Control groups showed no significant change in respiratory mechanics. Conclusion Therapeutic hypothermia canreduce some markers of injury and inflammation associated with ARDS. Further studies are required to determine the effect on longer term outcomes and mortality.

Adenomyosis is associated with specific proton nuclear magnetic resonance (1H-NMR) serum metabolic profiles

To determine whether the adenomyosis phenotype affects the proton nuclear magnetic resonance (1H-NMR)-based serum metabolic profile of patients. Cohort study. University hospital-based research center. Seventy-seven patients who underwent laparoscopy for a benign gynecologic condition. Pelvic magnetic resonance imaging and collection of a venous peripheral blood sample were performed during the preoperative workup. The women were allocated to the adenomyosis group (n = 32), or the control group (n = 45). The adenomyosis group was further subdivided into two groups: diffuse adenomyosis of the inner myometrium (n = 14) and focal adenomyosis of the outer myometrium (n = 18). Other adenomyosis phenotypes were excluded. Metabolomic profiling based on 1H-NMR spectroscopy in combination with statistical approaches. The serum metabolic profiles of the patients with adenomyosis indicated lower concentrations of 3-hydroxybutyrate, glutamate, and serine compared with controls. Conversely, the concentrations of proline, choline, citrate, 2-hydroxybutyrate, and creatinine were higher in the adenomyosis group. The focal adenomyosis of the outer myometrium and the diffuse adenomyosis phenotypes also each exhibited a specific metabolic profile. Serum metabolic changes were detected in women with features of adenomyosis compared with their disease-free counterparts, and a number of specific metabolic pathways appear to be engaged according to the adenomyosis phenotype. The metabolites with altered levels are particularly involved in immune activation as well as cell proliferation and cell migration. Nevertheless, this study did find evidence of a correlation between metabolite levels and symptoms thought to be related to adenomyosis. Further studies are required to determine the clinical significance of these differences in metabolic profiles.

Metabolic changes in the brain and blood of rats following acoustic trauma, tinnitus and hyperacusis.

It has been increasingly recognized that tinnitus is likely to be generated by complex network changes. Acoustic trauma that causes tinnitus induces significant changes in multiple metabolic pathways in the brain. However, it is not clear whether those metabolic changes in the brain could also be reflected in blood samples and whether metabolic changes could discriminate acoustic trauma, hyperacusis and tinnitus. We analyzed brain and serum metabolic changes in rats following acoustic trauma or a sham procedure using metabolomics. Hearing levels were recorded before and after acoustic trauma and behavioral measures to quantify tinnitus and hyperacusis were conducted at 4 weeks following acoustic trauma. Tissues from 11 different brain regions and serum samples were collected at about 3 months following acoustic trauma. Among the acoustic trauma animals, eight exhibited hyperacusis-like behavior and three exhibited tinnitus-like behavior. Using Gas chromatography-mass spectrometry and multivariate statistical analysis, significant metabolic changes were found in acoustic trauma animals in both the brain and serum samples with a number of metabolic pathways significantly perturbated. Furthermore, metabolic changes in the serum were able to differentiate sham from acoustic trauma animals, as well as sham from hyperacusis animals, with high accuracy. Our results suggest that serum metabolic profiling in combination with machine learning analysis may be a promising approach for identifying biomarkers for acoustic trauma, hyperacusis and potentially, tinnitus.

Analysis of metabolomics profile in hypothyroid patients before and after thyroid hormone replacement.

The serum metabolic changes occurring during the transition from hypothyroidism to euthyroidism are not known. This study aimed to determine the metabolomic profile in hypothyroid patients before (HypoT0) and after (HypoT1) euthyroidism achieved through levothyroxine (L-T4) treatment. Eighteen patients with overt primary hypothyroidism were recruited for the study. All patients were treated with L-T4 to achieve euthyroidism. Thyrotropin (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and metabolomics profiles were measured before and after 3months of treatment. The euthyroid control group consisted of 28 healthy volunteers. Metabolomics analysis was performed using Nuclear Magnetic Resonance (NMR) spectroscopy. 1H NMR-based metabolomics profiling of patients with newly diagnosed hypothyroidism (HypoT0) showed significantly higher levels of citrate, creatinine, glycerol, myo-inositol and serine, and lower levels of proline and taurine compared to controls. Interestingly, some metabolic changes were persistent three months after pharmacological treatments, despite normal serum TSH and thyroid hormone concentrations (HypoT1). When an Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) model was built to evaluate possible differences in the metabolic profile between HypoT0 and HypoT1, the data obtained were not significantly different. These results suggest that metabolic changes in the patients with hypothyroidism may persist after normalization of serum levels of FT3, FT4, and TSH, which currently represent the gold standard in laboratory testing for diagnosis and evaluation of thyroid pathology. So, the metabolomics approach may contribute to integrate classical hormone assays and to determine the euthyroid status achievement with greater efficacy.

Effects of Early Life Stress on Bone Homeostasis in Mice and Humans.

Bone pathology is frequent in stressed individuals. A comprehensive examination of mechanisms linking life stress, depression and disturbed bone homeostasis is missing. In this translational study, mice exposed to early life stress (MSUS) were examined for bone microarchitecture (μCT), metabolism (qPCR/ELISA), and neuronal stress mediator expression (qPCR) and compared with a sample of depressive patients with or without early life stress by analyzing bone mineral density (BMD) (DXA) and metabolic changes in serum (osteocalcin, PINP, CTX-I). MSUS mice showed a significant decrease in NGF, NPYR1, VIPR1 and TACR1 expression, higher innervation density in bone, and increased serum levels of CTX-I, suggesting a milieu in favor of catabolic bone turnover. MSUS mice had a significantly lower body weight compared to control mice, and this caused minor effects on bone microarchitecture. Depressive patients with experiences of childhood neglect also showed a catabolic pattern. A significant reduction in BMD was observed in depressive patients with childhood abuse and stressful life events during childhood. Therefore, future studies on prevention and treatment strategies for both mental and bone disease should consider early life stress as a risk factor for bone pathologies.

Diabetes Leads to Alterations in Normal Metabolic Transitions of Pregnancy as Revealed by Time-Course Metabolomics.

Women with diabetes during pregnancy are at increased risk of poor maternal and neonatal outcomes. Despite this, the effects of pre-gestational (PGDM) or gestational diabetes (GDM) on metabolism during pregnancy are not well understood. In this study, we utilized metabolomics to identify serum metabolic changes in women with and without diabetes during pregnancy and the cord blood at birth. We observed elevations in tricarboxylic acid (TCA) cycle intermediates, carbohydrates, ketones, and lipids, and a decrease in amino acids across gestation in all individuals. In early gestation, PGDM had elevations in branched-chain amino acids and sugars compared to controls, whereas GDM had increased lipids and decreased amino acids during pregnancy. In both GDM and PGDM, carbohydrate and amino acid pathways were altered, but in PGDM, hemoglobin A1c and isoleucine were significantly increased compared to GDM. Cord blood from GDM and PGDM newborns had similar increases in carbohydrates and choline metabolism compared to controls, and these alterations were not maternal in origin. Our results revealed that PGDM and GDM have distinct metabolic changes during pregnancy. A better understanding of diabetic metabolism during pregnancy can assist in improved management and development of therapeutics and help mitigate poor outcomes in both the mother and newborn.

Analysis of the metabolic pathways affected by hot-humid or dry climate based on fecal metabolomics coupled with serum metabolic changes in broiler chickens

Air temperature and relative humidity (RH) are 2 important climatic elements that affect animal welfare and health. The prevailing hot and humid or dry climate is one of the major constraints for optimum poultry production, especially in the tropics and subtropical regions. Many studies have suggested that exposure to hot-humid or dry climate is associated with a high risk of metabolic imbalance; however, the underlying metabolic changes caused by low or high RH climate is not yet well understood. Therefore, we used a comprehensive ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry–based metabolic profiling of fecal samples to explore the effects of hot-humid and dry climate on metabolic pathways in broilers. A total of 180 twenty-eight-day-old Arbor Acres broilers were randomly allocated to 3 treatments, each containing 6 replicates of 10 birds per treatment, using a completely randomized design. Birds were reared at 35, 60, or 85% RH at 32°C (temperature increased by 3°C every 3 d from 20°C to 32°C within 15 d: 20°C, 23°C, 26°C, 29°C, 32°C) for 15 d. Results showed that significant changes in the levels of 36 metabolites were detected. Evidence of changes in gluconeogenesis associated to pyruvate metabolism, galactose metabolism, and ABC transporter was observed. In addition, hot-humid and dry stress also affected the protein translation process caused by aminoacyl-tRNA biosynthesis, which may be associated with protein synthesis and hormone secretion disorders. Furthermore, we observed significant changes in primary bile acid biosynthesis and taurine and hypotaurine metabolism, which indicated that fat synthesis was affected. We also observed significant changes in arginine and proline metabolism and histidine metabolism, which were associated with skin vasodilation and blood flow. These results provide biochemical insights into metabolic changes due to hot-humid or dry climate.

Serum metabolic changes associated with dioxin exposure in a Chinese male cohort

Dioxins, a group of persistent organic pollutants, have been proved to correlate with ranges of diseases by activating the aryl hydrocarbon receptor (AhR). However, previous dioxin toxicity studies primarily focused on the activation of AhR with signaling pathways at gene and protein levels. The investigation of underlying mechanisms at the metabolic level is still necessary. In this study, serum samples of 48 and 47 healthy participants with the highest and lowest dioxin levels based on quartile distribution of the serum dioxin concentrations of 215 male adults were selected for metabolomics analysis by using liquid chromatography coupled with orbitrap high-resolution mass spectrometry to investigate dioxin-related metabolic responses. The identified potential biomarkers included acylcarnitines, fatty acids and derivatives, glycerophospholipids, etc. suggested that metabolic pathways such as fatty acid β-oxidation, essential fatty acid metabolism, arachidonic acid metabolism, glycerophospholipid and sphingolipid metabolism and purine metabolism were disturbed by dioxin exposure. The results indicated that people with high dioxin exposure levels were at the potential health risks of inflammation, liver and cardiovascular diseases. The metabolic findings may help understand the link between dioxin exposure and the diseases.

Metabolomic profiling of acute diabetes complications in children with type 1 diabetes mellitus

Acute type 1 diabetes mellitus (T1DM) complications – diabetes ketoacidosis (DKA) and hypoglycemia (HG) – are dangerous not only as a threat to patients’ life but also because of their long-term sequelae. Aim: Evaluation of serum metabolic changes caused by episode of DKA and HG, that can be detected despite restoring parameters typically changed during the episodes. Selection of putative long-standing biomarkers of past episodes of DKA and HG. Materials and methods: Four groups of children with T1DM were recruited: patients after episode of DKA and HG, children with established T1DM (EDM) and patients with newly diagnosed diabetes without diabetes ketoacidosis (NDM). Serum samples were collected in three group-specific time points (since the hospital admission): 0h – 24h – 72h for DKA and NDM group and 0h – 12h – 48h for HG group. From EDM patients only one sample was collected during running routine laboratory tests. Patients were assigned to two batches: DKA-NDM-EDM (N = 20x3, N = 10x3, N = 10) and HG-EDM- -NDM (N = 10x3, N = 25, N = 15x3). All patients within the batches were matched based on age and sex. Metabolic fingerprinting was performed with LC- -QTOF-MS (Agilent 6550 iFunnel). Results: In DKA batch after technical filtering 248 metabolomic features out of 712 (in positive ionization) and 295 out of 652 (in negative ionization) were suitable for between-group comparisons. Statistical analysis selected 22 metabolic features as putative biomarkers of episodes of DKA occurrence in nearest 72h. Decision tree to diagnose past DKA episode, based on two best metabolites, achieved sensitivity of 95% (CI (confidence interval): 81.79–99.13%) and specificity of 80% (CI: 67.30–88.81%). In HG batch after technical filtering 359 metabolomic features out of 1006 (in positive ionization) and 374 out of 763 (in negative ionization) were suitable for between-group comparisons. Statistical analysis selected 9 metabolic features as putative biomarkers of episodes of DKA occurrence in nearest 48h. Decision tree to diagnose past HG episode, based on two best metabolites, achieved sensitivity of 90% (CI: 72.32–97.38%) and specificity 80% (CI: 68.39–88.26%). Conclusions: Metabolic disturbances caused by DKA may be traced in serum up to 72h after the episode and for hypoglycemia up to 48h.

1H-NMR Metabolomics Analysis of the Effect of Rubusoside on Serum Metabolites of Golden Hamsters on a High-Fat Diet.

Rubusoside is a natural sweetener and the active component of Rubus suavissimus. The preventive and therapeutic effect of rubusoside on high-fat diet-induced (HFD) serum metabolite changes in golden hamsters was analyzed by 1H-NMR metabolomics to explore the underlying mechanism of lipid metabolism regulation. 1H-NMR serum metabolomics analyses revealed a disturbed amino acid-, sugar-, fat-, and energy metabolism in HFD animals. Animals supplemented with rubusoside can partly reverse the metabolism disorders induced by high-fat diet and exerted good anti-hypertriglyceridemia effect by intervening in some major metabolic pathways, involving amino acid metabolism, synthesis of ketone bodies, as well as choline and 4-hydroxyphenylacetate metabolism. This study indicates that rubusoside can interfere with and normalize high-fat diet-induced metabolic changes in serum and could provide a theoretical basis to establish rubusoside as a potentially therapeutic tool able to revert or prevent lipid metabolism disorders.