Prevalence of Selected Polymorphisms of Il7R, CD226, CAPSL, and CLEC16A Genes in Children and Adolescents with Autoimmune Thyroid Diseases.

Hashimoto's thyroiditis (HT) and Graves' disease (GD) are common autoimmune endocrine disorders in children. Studies indicate that apart from environmental factors, genetic background significantly contributes to the development of these diseases. This study aimed to assess the prevalence of selected single-nucleotide polymorphisms (SNPs) of Il7R, CD226, CAPSL, and CLEC16A genes in children with autoimmune thyroid diseases. We analyzed SNPs at the locus rs3194051, rs6897932 of IL7R, rs763361 of CD226, rs1010601 of CAPSL, and rs725613 of CLEC16A gene in 56 HT patients, 124 GD patients, and 156 healthy children. We observed significant differences in alleles IL7R (rs6897932) between HT males and the control group (C > T, p = 0.028) and between all GD patients and healthy children (C > T, p = 0.035) as well as GD females and controls (C > T, p = 0.018). Moreover, the C/T genotype was less frequent in GD patients at rs6897932 locus and in HT males at rs1010601 locus. The presence of the T allele in the IL7R (rs6897932) locus appears to have a protective effect against HT in males and GD in all children. Similarly, the presence of the T allele in the CAPSL locus (rs1010601) seems to reduce the risk of HT development in all patients.

Overnight Corticosterone and Gene Expression in Mouse Hippocampus: Time Course during Resting Period.

The aim of the experiment was to test the effect of an elevated level of glucocorticoids on the mouse hippocampal transcriptome after 12 h of treatment with corticosterone that was administered during an active phase of the circadian cycle. Additionally, we also tested the circadian changes in gene expression and the decay time of transcriptomic response to corticosterone. Gene expression was analyzed using microarrays. Obtained results show that transcriptomic responses to glucocorticoids are heterogeneous in terms of the decay time with some genes displaying persistent changes in expression during 9 h of rest. We have also found a considerable overlap between genes regulated by corticosterone and genes implicated previously in stress response. The examples of such genes are Acer2, Agt, Apod, Aqp4, Etnppl, Fabp7, Fam107a, Fjx1, Fmo2, Galnt15, Gjc2, Heph, Hes5, Htra1, Jdp2, Kif5a, Lfng, Lrg1, Mgp, Mt1, Pglyrp1, Pla2g3, Plin4, Pllp, Ptgds, Ptn, Slc2a1, Slco1c1, Sult1a1, Thbd and Txnip. This indicates that the applied model is a useful tool for the investigation of mechanisms underlying the stress response.

Ghrelin, Obestatin and Their Receptors As Well As Metabotropic Glutamate Receptor Assessment in Chronic Functional Constipation in Children.

OBJECTIVES: The aim of this study was to examine the role of ghrelin, obestatin, and glutamate and their receptors in the pathogenesis of children functional constipation. METHODS: Children ages 4-17 were the subject of the study: 121 children with constipation (55 boys and 66 girls), 36 patients of the same age (26 boys and 10 girls) were the controls. Expression of ghrelin, obestatin, and glutamate receptors on gastric and colon specimens taken by endoscopy were assessed. The concentration of the above agents was estimated in serum by the enzyme-linked immunosorbent assay test. RESULTS: The lower median serum concentrations of ghrelin, in the constipated children than in controls were confirmed (1.9 ng/mL vs 2.6 ng/mL, P < 0.05). The expression of the metabotropic receptor 7 for glutamate (mGlu7) RNA was higher in the stomach (32.49 vs 31.47, P < 0.05), and was lower in the rectum in constipated patients compared to the control group (31.76 vs 32.62, P < 0.05). A negative correlation between the concentration of ghrelin in serum and colonic transient time (P = 0.01, rho = -0.23) was shown in the study group.Higher median expression of obestatin receptor G protein-coupled receptor39 in rectal mucosae was found in a constipated group than in the controls (29.9 vs 26.9, P < 0.05). CONCLUSION: Ghrelin, and receptors for ghrelin, obestatin, and glutamate in gastrointestinal mucosa play a role in the pathogenesis of functional constipation in children.

Dyssynergic Defecation and Anal Sphincter Disorders in Children in High-Resolution Anorectal Manometry Investigation.

OBJECTIVES: Dyssynergic defecation is a common disorder in children with functional constipation (FC) because of relaxation disorders of the sphincter apparatus and intra-rectal pressure during defecation. The aim of the study was to determine frequency and type of dyssynergic defecation and to assess pressure in the anal canal poles during simulated evacuation and function of puborectalis muscle in defecation in children with FC. METHODS: Three-dimensional (3D) high-resolution anorectal manometries (3D HRAM) were performed in 131 children with FC. In the manometric test, resting pressure measurements were assessed in 4 measuring poles of the anal canal. RESULTS: One hundred thirty-one children ages 5 to 17 years (mean age 10.2; SD ±â€Š3.8; median 10) were involved in the study (69 girls and 62 boys). Dyssynergic defecation was shown in 106/131 (80.9%) examined children. A statistically significant difference between the age of examined children (P < 0.02) and intrarectal pressures at the anal canal measuring points (left P < 0.009, right P < 0.005, anterior P < 0.01) was found. Correlation between the residual pressure values in lateral anal canal measurement poles and intrarectal pressure was demonstrated in all types of dyssynergy (left: r = 0.69, P < 0.0005; right: r = 0.74, P < 0.0005). In a group of 53/131 (40.5%) children, 3D HRAM showed a rectal pressure increase during simulated defecation, because of the dysfunction of the puborectalis muscle. CONCLUSION: The increase in sphincter pressure in lateral and posterior poles in I and II types of dyssynergia and in lateral poles in other types of dyssynergia may depend on relaxation disorders of the puborectalis muscle during defecation.

The MC4R genetic variants are associated with lower visceral fat accumulation and higher postprandial relative increase in carbohydrate utilization in humans.

PURPOSE: The interactions between lifestyle and genetic factors play an important role in obesity development. Mutations in melanocortin-4-receptor (MC4R) gene are one of the most common cause of monogenic obesity, however, the functional effects of polymorphic variants near MC4R gene in general populations remain uncertain. The aim of our study was to analyze whether the common single nucleotide polymorphisms (SNPs) of MC4R gene influence the food preferences, physical activity, body fat content and distribution, as well as fasting and postprandial energy expenditure and substrates utilization. METHODS: We genotyped previously identified MC4R SNPs: rs17782313, rs633265, rs1350341, rs12970134 in 927 subjects, who underwent anthropometric, total body fat content, visceral (VAT) and subcutaneous adipose tissue (SAT) measurements, and daily physical activity and dietary intake analysis. In randomly selected 47 subjects the energy expenditure, carbohydrate and lipid utilizations were evaluated in fasting state and after high-carbohydrate and control meals intake. RESULTS: We found the significant associations between studied SNPs of MC4R gene and VAT and VAT/SAT ratio. Moreover, the GG genotype carriers of rs1350341, who had the lowest VAT accumulation (p = 0.012), presented higher relative increase in postprandial carbohydrate utilization (p = 0.013, p = 0.024). CONCLUSIONS: We have observed that common SNPs of the MC4R gene influence the body fat content and distribution, as well as relative increase in postprandial carbohydrate utilization. We believe that our study may help to understand better the impact of MC4R gene on obesity development, and to help to provide personalized prevention/treatment strategies to fight against obesity and its metabolic consequences.

Association between polymorphisms of a folate - homocysteine - methionine - SAM metabolising enzyme gene and multiple sclerosis in a Polish population.

BACKGROUND AND OBJECTIVES: Multiple sclerosis (MS) is a chronic inflammatory, autoimmune disease with a still unknown aetiology. The main initial mechanism of demyelination and injury to the central nervous system (CNS) appears to be inflammation. Neurotoxicity induced by homocysteine (Hcy) may be a factor affecting this process. 5,10-methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme involved in Hcy metabolism. It leads to Hcy remethylation to methionine. In the present study, we aimed to investigate a possible association between two variants of MTHFR gene in patients with MS in Poland and healthy individuals. METHODS: In this study, we genotyped 174 relapsing-remitting MS patients and 186 healthy controls using the TaqMan technique. RESULTS AND CONCLUSIONS: It was found that, regardless of the presence of a specific allele, the gender of MS patients affects age at the time of the clinical onset of the disease: in rs1801133 for the C allele and T, the average age was 35 years for women and 29 for men (p = 0.0004; p = 0.034 respectively). Similarly for the second polymorphism rs1801131 for the A allele and C, the average age was 35 years for women and 29 for men (p = 0.001; p = 0.01 respectively). No significant allelic / genotypic frequency differences have been observed between the studied groups (c.677C > T, CT/TT p = 0.719, p = 0.262; c.1298A > C, AC/CC of p = 0.686; p = 0.66). We found no association between polymorphisms of a folate-homocysteine-methionine-SAM metabolising gene enzyme and multiple sclerosis in a Polish population.

Angiogenic factor screening in women with mild preeclampsia - New and significant proteins in plasma.

INTRODUCTION: The aim of this study was to analyse a panel of 60 angiogenic factors (pro-angiogenic and antiangiogenic) in the plasma of women with mild preeclampsia. MATERIALS AND METHODS: We recruited 21 women between 25 and 40 weeks gestation with diagnosed mild preeclampsia into the study group and 27 healthy women with uncomplicated pregnancies of corresponding gestational age to that of the study to the control group. We used a quantitative protein macroarray method that allowed for analysis of 60 angiogenic proteins per sample simultaneously. RESULTS: We showed a statistically significant increase in the concentration of 8 proteins, interferon gamma (IFN-γ), interleukin 6 (IL-6), leukaemia inhibitory factor (LIF), heparin-binding EGF-like growth factor (HB-EGF), hepatocyte growth factor (HGF), C-X-C motif chemokine 10 (IP-10), leptin and platelet-derived growth factor BB (PDGF-BB), as well as a significant decrease in the concentration of 3 proteins, vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and follistatin, in the plasma of women with preeclampsia. CONCLUSION: Based on our findings, it seems that protein factors may play an important role in the pathogenesis of preeclampsia, and there are many proteins that have not been studied in PE to date. There are no previous studies assessing the LIF, follistatin, HGF, HB-EGF and PDGF-BB concentrations in the plasma of women with PE; therefore, our obtained results indicate that these proteins are new factors that can play an important role in the pathomechanisms of PE.

The relationship between the leptin/ghrelin ratio and meals with various macronutrient contents in men with different nutritional status: a randomized crossover study.

BACKGROUND: Hormones, which influence satiety and hunger, play a significant role in body energy balance regulation. Ghrelin is a peptide that plays an important role in short-term appetite regulation, whereas leptin is a factor that controls long-term energy balance and is considered as a satiety hormone. The aim of this study was to evaluate the leptin/ghrelin ratio in a fasting state and after the intake of meals with varying macronutrient contents and to assess the possible differences between normal body weight and overweight/obese men. METHODS: We examined 46 healthy adult men (23 with normal body weight and 23 overweight/obese) aged 21-58, who were divided into two groups. In the crossover study, participants received isocaloric (450 kcal) meals with different macronutrient contents: men from the first group received high-carbohydrate (HC) and normo-carbohydrate (NC) meals, and in the second group, participants received high-carbohydrate and high-fat (HF) meals. The ratio of leptin/ghrelin levels was calculated from leptin and total ghrelin serum concentrations in a fasting state and 30, 60, 120, 180 and 240 min after meal intake. One-way ANOVA and Wilcoxon signed-rank tests were carried out. The normality of the variable distribution was checked with the Shapiro-Wilk test, the homogeneity of variances was verified with the Levene test, and the false discovery rate p-value adjustment method was used. RESULTS: The leptin/ghrelin ratio was significantly higher in overweight/obese men than individuals with normal body weight in a fasting state, as well as postprandially. We observed trends towards a higher leptin/ghrelin ratio values from the 60 min after HC-meal intake compared to the NC- and HF-meals in normal body weight participants, while in overweight/obese men, we did not note any significant differences dependent on the meal type. CONCLUSIONS: We have observed a significantly different postprandial leptin/ghrelin ratio in normal body weight and overweight/obese men, and our results suggest that in men with normal body weight, a greater feeling of satiety may occur after high-carbohydrate meal intake, which was not noted in the overweight/obese individuals.

Maternal Plasma Metabolomic Profiles in Spontaneous Preterm Birth: Preliminary Results.

OBJECTIVE: To profile maternal plasma metabolome in spontaneous preterm birth. METHOD: In this retrospective case-control study, we have examined plasma of patient with preterm birth (between 22 and 36 weeks of pregnancy (n = 57)), with threatened preterm labor (between 23 and 36 weeks of pregnancy (n = 49)), and with term delivery (n = 25). Plasma samples were analysed using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) in positive and negative polarity modes. RESULTS: We found 168 differentially expressed metabolites that were significantly distinct between study groups. We determined 51 metabolites using publicly available databases that could be subdivided into one of the five groups: amino acids, fatty acids, lipids, hormones, and bile acids. PLS-DA models, verified by SVM classification accuracy, differentiated preterm birth and term delivery groups. CONCLUSIONS: Maternal plasma metabolites are different between term and preterm parturitions. Part of them may be related with preterm labor, while others may be affected by gestational age or the beginning of labor. Metabolite profile can classify preterm or term delivery groups raising the potential of metabolome as a biomarker to identify high-risk pregnancies. Metabolomic studies are also a tool to detect individual compounds that may be further tested in targeted researches.

Amniotic Fluid Angiogenic and Inflammatory Factor Profiling in Foetal Down Syndrome.

OBJECTIVES: Angiogenic factors are proteins that can potentially be related to certain foetal chromosomal abnormalities. The goal of this study was to determine the concentrations of 60 angiogenic factors in the amniotic fluid of women carrying foetuses with Down syndrome (DS). METHODS: After analysis of the karyotyping results, for the purpose of this study, we chose 12 women with foetal DS. For the control group, we selected 12 healthy patients with uncomplicated pregnancies (15-18 weeks of gestation) who delivered healthy newborns at term. To assess the concentrations of proteins in the amniotic fluid, we used a protein macroarray, which enabled the simultaneous determination of 60 angiogenic factors per sample. RESULTS: In the amniotic fluid of women with foetal DS compared to patients with healthy foetuses, we reported significant decreases in the concentrations of 14 angiogenic factors, including leptin, angiopoietin 1 (ANG-1), angiostatin, epidermal growth factor (EGF), interleukin 1-beta (IL-1b), interleukin 4 (IL-4), interleukin 12p40 (IL-12p40), monocyte chemotactic protein 2 (MCP-2), matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-9 (MMP-9), platelet endothelial cell adhesion molecule 1 (PECAM-1), transforming growth factor alpha (TGF alpha), vascular endothelial growth factor 2 (VEGFR2), and vascular endothelial growth factor 3 (VEGFR3). CONCLUSIONS: Based on our findings, we hypothesise that angiogenic factors may play roles in the pathogenesis of DS. Defining the factors' potential as biochemical factors of DS requires further investigation in a larger group of patients.

Usefulness of copeptin as a potential biomarker in TBE.

OBJECTIVE: The aim of the study was to evaluate the usefulness of copeptin for differentiation of hyponatremia in the course of tick-borne encephalitis (TBE) and for being a prognostic marker of the severity of TBE. MATERIALS AND METHODS: One hundred and fourteen patients with TBE were included in the study. The control group consisted of 62 patients diagnosed with viral meningitis. RESULTS: Copeptin concentration did not differ in patients with hyponatremia and normonatremia. Urinary sodium excretion to plasma copeptin (copeptin/UNa Secretion) ratio was significantly lower in Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Secretion patients than in patients with hyponatremia of other origin. Mean copeptin concentration in TBE patients was higher than in control group (VM) patients. There were no differences between patients with severe and mild course of TBE. CONCLUSIONS: Copeptin/UNa ratio may be used as a potential biomarker of SIADH in patients with TBE. Copeptin concentration is significantly higher in patients with TBE than in viral meningitis of other origin, especially in patients aged 18-34 and >49 years old. Copeptin does not differentiate TBE of mild and severe course.

Social stress increases expression of hemoglobin genes in mouse prefrontal cortex.

BACKGROUND: In order to better understand the effects of social stress on the prefrontal cortex, we investigated gene expression in mice subjected to acute and repeated social encounters of different duration using microarrays. RESULTS: The most important finding was identification of hemoglobin genes (Hbb-b1, Hbb-b2, Hba-a1, Hba-a2, Beta-S) as potential markers of chronic social stress in mice. Expression of these genes was progressively increased in animals subjected to 8 and 13 days of repeated stress and was correlated with altered expression of Mgp (Mglap), Fbln1, 1500015O10Rik (Ecrg4), SLC16A10, and Mndal. Chronic stress increased also expression of Timp1 and Ppbp that are involved in reaction to vascular injury. Acute stress did not affect expression of hemoglobin genes but it altered expression of Fam107a (Drr1) and Agxt2l1 (Etnppl) that have been implicated in psychiatric diseases. CONCLUSIONS: The observed up-regulation of genes associated with vascular system and brain injury suggests that stressful social encounters may affect brain function through the stress-induced dysfunction of the vascular system.

Hepatic transcriptome profiling identifies differences in expression of genes associated with changes in metabolism and postnatal growth between Hereford and Holstein-Friesian bulls.

This study examined liver transcriptomic profiles of cattle distinctly different in meat and milk production capacity. It was performed on bulls of two different genetic backgrounds: Herefords (H), a meat breed, and Holstein-Friesians (HF), a dairy breed. Using bovine long oligo-microarrays and qPCR, we identified 128 genes that are differentially expressed between the two breeds. In H bulls, we observed up-regulation of genes involved in fatty acid biosynthesis and lipid metabolism (CD36, CAT, HSD3B1, FABP1, ACAA1) and involved in insulin signaling (INSR, INSIG2, NR4A1) and down-regulation of genes involved in somatotropic axis signaling (IGF1, GHR, IGFBP3) as compared to HF. Transcriptome profiling of these two breeds allowed us to pinpoint the transcriptional differences between Holstein and Hereford bulls at hepatic level associated with changes in metabolism and postnatal growth.

Stress susceptibility-specific phenotype associated with different hippocampal transcriptomic responses to chronic tricyclic antidepressant treatment in mice.

BACKGROUND: The effects of chronic treatment with tricyclic antidepressant (desipramine, DMI) on the hippocampal transcriptome in mice displaying high and low swim stress-induced analgesia (HA and LA lines) were studied. These mice displayed different depression-like behavioral responses to DMI: stress-sensitive HA animals responded to DMI, while LA animals did not. RESULTS: To investigate the effects of DMI treatment on gene expression profiling, whole-genome Illumina Expression BeadChip arrays and qPCR were used. Total RNA isolated from hippocampi was used. Expression profiling was then performed and data were analyzed bioinformatically to assess the influence of stress susceptibility-specific phenotypes on hippocampal transcriptomic responses to chronic DMI. DMI treatment affected the expression of 71 genes in HA mice and 41 genes in LA mice. We observed the upregulation of Igf2 and the genes involved in neurogenesis (HA: Sema3f, Ntng1, Gbx2, Efna5, and Rora; LA: Otx2, Rarb, and Drd1a) in both mouse lines. In HA mice, we observed the upregulation of genes involved in neurotransmitter transport, the termination of GABA and glycine activity (Slc6a11, Slc6a9), glutamate uptake (Slc17a6), and the downregulation of neuropeptide Y (Npy) and corticotropin releasing hormone-binding protein (Crhbp). In LA mice, we also observed the upregulation of other genes involved in neuroprotection (Ttr, Igfbp2, Prlr) and the downregulation of genes involved in calcium signaling and ion binding (Adcy1, Cckbr, Myl4, Slu7, Scrp1, Zfp330). CONCLUSIONS: Several antidepressant treatment responses are similar in individuals with different sensitivities to stress, including the upregulation of Igf2 and the genes involved in neurogenesis. However, the findings also reveal that many responses to antidepressant treatments, involving the action of individual genes engaged in neurogenesis, neurotransmitter transport and neuroprotection, depend on constitutive hippocampal transcriptomic profiles and might be genotype dependent. The results suggest that, when and if this becomes feasible, antidepressant treatment should take into consideration individual sensitivity to stress.

Long-term effects of COVID-19 on the endocrine system - a pilot case-control study.

Background: Coronavirus disease 2019 (COVID-19) has permanently changed the world. Despite having been a pandemic for nearly 3 years, the mid- and long-term complications of this disease, including endocrine disorders, remain unclear. Our study aimed to evaluate the lasting effects of COVID-19 on the endocrine system 6 months after initial infection. Methods: We compared patients who underwent COVID-19 to age- and sex-matched subjects from a population-based study conducted before the pandemic. We evaluated differences in multiple parameters related to metabolism and the endocrine system including fasting glucose, insulin, lipids, body composition, thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), anti-thyroglobulin (aTG) and anti-thyroid peroxidase (aTPO) antibodies, prolactin, cortisol, testosterone, and estradiol. Results: We found significantly lower levels of fT3 and fT4, accompanied by higher levels of TSH and aTPO antibodies, in COVID-19 survivors. Moreover, we found that patients who underwent SARS-CoV2 infection had higher levels of prolactin and lower levels of testosterone than controls. Interestingly, differences in testosterone levels were observed only in male subjects. We did not detect significant differences in body composition or metabolic and glycemic parameters between cases and controls, except for significantly higher values of the HOMA2-B index in COVID-19 survivors. Conclusion: Our study indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection might have long-term consequences on the endocrine system, including the suppressed function of the thyroid gland, prolactin, and male sex hormone secretion. Moreover, we showed that in a 6-month follow-up, COVID-19 had no consequences on glycemic parameters, lipid profiles, liver function, body composition, cortisol levels, and estradiol levels.

Stress and the brain transcriptome: Identifying commonalities and clusters in standardized data from published experiments.

Interpretation of transcriptomic experiments is hindered by many problems including false positives/negatives inherent to big-data methods and changes in gene nomenclature. To find the most consistent effect of stress on brain transcriptome, we retrieved data from 79 studies applying animal models and 3 human studies investigating post-traumatic stress disorder (PTSD). The analyzed data were obtained either with microarrays or RNA sequencing applied to samples collected from more than 1887 laboratory animals and from 121 human subjects. Based on the initial database containing a quarter million differential expression effect sizes representing transcripts in three species, we identified the most frequently reported genes in 223 stress-control comparisons. Additionally, the analysis considers sex, individual vulnerability and contribution of glucocorticoids. We also found an overlap between gene expression in PTSD patients and animals which indicates relevance of laboratory models for human stress response. Our analysis points to genes that, as far as we know, were not specifically tested for their role in stress response (Pllp, Arrdc2, Midn, Mfsd2a, Ccn1, Htra1, Csrnp1, Tenm4, Tnfrsf25, Sema3b, Fmo2, Adamts4, Gjb1, Errfi1, Fgf18, Galnt6, Slc25a42, Ifi30, Slc4a1, Cemip, Klf10, Tom1, Dcdc2c, Fancd2, Luzp2, Trpm1, Abcc12, Osbpl1a, Ptp4a2). Provided transcriptomic resource will be useful for guiding the new research.

Hypothalamic Neurochemical Changes in Long-Term Recovered Bilateral Subdiaphragmatic Vagotomized Rats.

Background: Vagus nerve is one of the crucial routes in communication between the immune and central nervous systems. The impaired vagal nerve function may intensify peripheral inflammatory processes. This effect subsides along with prolonged recovery after permanent nerve injury. One of the results of such compensation is a normalized plasma concentration of stress hormone corticosterone - a marker of hypothalamic-pituitary-adrenal (HPA) axis activity. In this work, we strive to explain this corticosterone normalization by studying the mechanisms responsible for compensation-related neurochemical alterations in the hypothalamus. Materials and Methods: Using microarrays and high performance liquid chromatography (HPLC), we measured genome-wide gene expression and major amino acid neurotransmitters content in the hypothalamus of bilaterally vagotomized rats, 1 month after surgery. Results: Our results show that, in the long term, vagotomy affects hypothalamic amino acids concentration but not mRNA expression of tested genes. Discussion: We propose an alternative pathway of immune to CNS communication after vagotomy, leading to activation of the HPA axis, by influencing central amino acids and subsequent monoaminergic neurotransmission.

Untargeted Metabolomics Analysis of the Serum Metabolic Signature of Childhood Obesity.

Obesity rates among children are growing rapidly worldwide, placing massive pressure on healthcare systems. Untargeted metabolomics can expand our understanding of the pathogenesis of obesity and elucidate mechanisms related to its symptoms. However, the metabolic signatures of obesity in children have not been thoroughly investigated. Herein, we explored metabolites associated with obesity development in childhood. Untargeted metabolomic profiling was performed on fasting serum samples from 27 obese Caucasian children and adolescents and 15 sex- and age-matched normal-weight children. Three metabolomic assays were combined and yielded 726 unique identified metabolites: gas chromatography-mass spectrometry (GC-MS), hydrophilic interaction liquid chromatography coupled to mass spectrometry (HILIC LC-MS/MS), and lipidomics. Univariate and multivariate analyses showed clear discrimination between the untargeted metabolomes of obese and normal-weight children, with 162 significantly differentially expressed metabolites between groups. Children with obesity had higher concentrations of branch-chained amino acids and various lipid metabolites, including phosphatidylcholines, cholesteryl esters, triglycerides. Thus, an early manifestation of obesity pathogenesis and its metabolic consequences in the serum metabolome are correlated with altered lipid metabolism. Obesity metabolite patterns in the adult population were very similar to the metabolic signature of childhood obesity. Identified metabolites could be potential biomarkers and used to study obesity pathomechanisms.

Syndecan 4, galectin 2, and death receptor 3 (DR3) as novel proteins in pathophysiology of preeclampsia.

INTRODUCTION: Preeclampsia has the highest rate of obstetric morbidity and mortality. METHODS: We recruited 21 women with preeclampsia and 27 women with uncomplicated pregnancies. We used a quantitative protein macroarray that allowed for analysis of 40 proteins. RESULTS: We found a statistically significant increase in the concentration of DR3, LIF and a significant decrease of VEGF, PlGF, syndecan-4 and galectin-2, in the plasma of women with preeclampsia. CONCLUSIONS: There are no previous studies assessing syndecan 4, galectin 2, and DR3 concentrations in women with preeclampsia; Our results indicate these proteins are new factors that play important roles in the immunological pathomechanism of preeclampsia.

The Response of Mitochondrial Respiration and Quantity in Skeletal Muscle and Adipose Tissue to Exercise in Humans with Prediabetes.

BACKGROUND: Mitochondrial dysfunction has been implicated in the pathogenesis of type 2 diabetes, but its contribution to the early stages of dysglycemia remains poorly understood. By collecting a high-resolution stage-based spectrum of dysglycemia, our study fills this gap by evaluating derangement in both the function and quantity of mitochondria. We sampled mitochondria in skeletal muscle and subcutaneous adipose tissues of subjects with progressive advancement of dysglycemia under a three-month exercise intervention. METHODS: We measured clinical metabolic parameters and gathered skeletal muscle and adipose tissue biopsies before and after the three-month exercise intervention. We then assayed the number of mitochondria via citrate synthase (CS) activity and functional parameters with high-resolution respirometry. RESULTS: In muscle, there were no differences in mitochondrial quantity or function at baseline between normoglycemics and prediabetics. However, the intervention caused improvement in CS activity, implying an increase in mitochondrial quantity. By contrast in adipose tissue, baseline differences in CS activity were present, with the lowest CS activity coincident with impaired fasting glucose and impaired glucose tolerance (IFG + IGT). Finally, CS activity, but few of the functional metrics, improved under the intervention. CONCLUSIONS: We show that in prediabetes, no differences in the function or amount of mitochondria (measured by CS activity) in skeletal muscle are apparent, but in adipose tissue of subjects with IFG + IGT, a significantly reduced activity of CS was observed. Finally, metabolic improvements under the exercise correlate to improvements in the amount, rather than function, of mitochondria in both tissues.