Project description:We analyzed the transcriptomic profiles of human podocyte-like epithelial cells (HUPEC) obtained from urine of two subjects with APOL1 low-risk (G0/G0) genotypes and two subjects with APOL1 high-risk (G1/G2) genotypes.
Project description:We analyzed the small RNA profiles of human podocyte-like epithelial cells (HUPEC) obtained from urine of two subjects with APOL1 low-risk (G0/G0) genotypes and two subjects with APOL1 high-risk (G1/G2) genotypes.
Project description:The aim of this study is to investigate the relationship between a-tocopherol levels and serum protein profiles in human subjects at risk of T2D before and after intake of adequate dairy (AD) or high dairy (HD) products. In this crossover study, dietary intake of 25 subjects with hyperinsulinemia included: 1- pre-AD intake; 2- pre-HD intake; 3- post- AD intake (less or equal 2 servings/day); and 4- post-HD intake (more or equal than 4 servings/day) assessed by food frequency questionnaire. At each intake, serum a-tocopherol level was measured by gas chromatography-spectrometry and serum proteins were identified and quantified by liquid chromatography-mass spectrometry. Spearman correlation and gene ontology analyses were performed to identify biological pathways affected by dairy intake. a-tocopherol levels were associated with proteins that regulate lipid homeostasis and immune response. However, the increase intake of dairy products modified these associations in subjects with T2D.
Project description:Skeletal muscle is one of the primary tissues involved in the development of type 2 diabetes (T2D). Obesity is tightly associated with T2D, making it challenging to isolate specific effects attributed to the disease alone. By using an in vitro myocyte model system we were able to isolate the inherent properties retained in myocytes originating from donor muscle precursor cells, without being confounded by varying extracellular factors present in the in vivo environment of the donor. We generated and characterized transcriptional profiles of myocytes from 24 human subjects, using a factorial design with two levels each of the factors T2D (healthy or diseased) and obesity (non-obese or obese), and determined the influence of each specific factor on genome-wide transcription. We identified a striking similarity of the transcriptional profiles associated independently with T2D or obesity. Obesity thus presents an inherent phenotype in skeletal myocytes, similar to that induced by T2D. Through bioinformatics analysis we found a candidate epigenetic mechanism, H3K27me3 histone methylation, mediating the observed transcriptional signatures. Functional characterization of the expression profiles revealed dysregulated myogenesis and down-regulated muscle function in connection with T2D and obesity, as well as up-regulation of genes involved in inflammation and the extracellular matrix. Further on, we identified a metabolite subnetwork involved in sphingolipid metabolism and affected by transcriptional up-regulation in T2D. Collectively, these findings pinpoint transcriptional changes that are hard-wired in skeletal myocytes in connection with both obesity and T2D.
Project description:<p>The relationship between dyslipidemia and type 2 diabetes mellitus (T2D) has been extensively reported, but the global lipid profiles, especially in the East Asia population, associated with the development of T2D remain to be characterized. Liquid chromatography coupled to tandem mass spectrometry was applied to detect the global lipidome in the fasting plasma of 293 Chinese individuals, including 114 T2D patients, 81 prediabetic subjects and 98 individuals with normal glucose tolerance (NGT). Both qualitative and quantitative analyses revealed a gradual change in plasma lipid features with T2D patients exhibiting characteristics close to those of prediabetic individuals, whereas they differed significantly from individuals with NGT. We constructed and validated a random forest classifier with 28 lipidomic features that effectively discriminated T2D from NGT or prediabetes. Most of the selected features significantly correlated with diabetic clinical indices. Hydroxybutyrylcarnitine was positively correlated with fasting plasma glucose, 2-hour postprandial glucose, glycated hemoglobin and insulin resistance index (HOMA-IR). Lysophosphatidylcholines such as lysophosphatidylcholine (18:0), lysophosphatidylcholine (18:1) and lysophosphatidylcholine (18:2) were all negatively correlated with HOMA-IR. The altered plasma lipidome in Chinese T2D and prediabetic subjects suggests that lipid features may play a role in the pathogenesis of T2D and that such features may provide a basis for evaluating risk and monitoring disease development.</p>
Project description:We have performed gene expression microarray analysis to profile transcriptomic signatures between insulin resistance high risk subjects and insulin resistance low risk subjects
Project description:To explore the possibility that DNAm-derived biological age is associated with mortality independently of common risk factors in subjects with type 2 diabetes (T2D), we leveraged a well-characterized cohort of individuals with T2D and followed-up for 16.8 years to create two groups, one of deceased individuals and the other of survived patients, fully matched for common risk factors. We performed a genome wide DNAm analysis of peripheral blood leukocytes to explore differentially methylated genes related to death in T2D, test the ability of a chosen set of existing tools estimating biological aging from DNAm to predict mortality, and assess the differences between deceased and survived diabetic patients in DNAm-inferred levels of selected inflammatory proteins and in predicted blood cell counts with a known pathophysiological role in T2D.
Project description:Genome wide DNA methylation profiling of normal colon samples. The Illumina Infinium HumanMethylation450 and EPIC Beadchip arrays were used to obtain DNA methylation profiles across approximately 450,000 and 850,000 CpGs. Samples were from nomal colons of 334 subjects with low, medium or high CRC risk according to their personal adenoma or cancer history.
Project description:White adipose tissue (WAT) dysfunction along with an aberrant expression of miRNAs are strongly associated with the risk of developing type 2 diabetes (T2D) with limited evidence linking early changes in the WAT-derived miRNAs and T2D. The present study aims to identify early miRNome changes prognostic for T2D in mice and humans. Gonadal (g) WAT of diabetes-resistant and -prone mice were subjected to multi-omics analyses (transcriptome, miRNome, methylome, proteome). Metabolic phenotypes linked with T2D were correlated with adipose tissue miRNA expression and DNA methylation from 14 monozygotic twin pairs discordant for T2D. Plasma miRNA levels from females at high risk of developing T2D (TÜF study) were included. Adipose tissue of the diabetes-susceptible mice was less insulin sensitive with 150 differentially expressed miRNAs compared to diabetes-resistant mice. Integrative analysis of miRNome-transcriptome-proteome identified 61 proteins involved in actin cytoskeleton, amino acid and sphingolipid metabolism. More than 20 miRNAs are located in the imprinted region Dlk1-Gtl2 and miR-335 in Mest and regulated by DNA methylation. Imprinted miRNAs also exhibited similar alteration in monozygotic twin pairs discordant for T2D with miR-335 expression altered only in females. Moreover, plasma levels of miR-335-5p were negatively correlated with fasting blood glucose in female individuals at high risk of developing T2D. Early alterations of WAT-derived miRNAs such as miR-335-5p could contribute to systemic metabolic changes associated with the risk of developing T2D.