Genome wide gene expression profiling of visceral adipose tissue among Asian Indian diabetics
ABSTRACT: Genes showing differential expression in visceral adipose tissue obtained from Asia Indian obese women suffering from type-2 diabetes mellitus as compared to age and BMI matched normal glucose tolerant women were identified by genome wide transcriptomic profiling in 5 diabetic and 5 control subjects respectively. Overall design: In this study, omental biopsies were obtained from 5 diabetic and 5 control women undergoing cholecystectomy. All the subjects age > 55 years, BMI > 30, free from infection and malignancy. Expression profiling of 32878 probes for 29,098 genes was done in all participants. A matrix file containing both processed and raw data is linked below as a supplementary file.
INSTRUMENT(S): ABI Human Genome Survey Microarray Version 2
Project description:Obesity-induced white adipose tissue (WAT) fibrosis is believed to accelerate WAT dysfunction. Two progenitor populations could be distinguished in omental white adipose tissue (oWAT) of morbidly obese individuals based on CD9 expression. In addition, the frequency of CD9high progenitors in oWAT correlates with oWAT fibrosis level, insulin-resistance severity and type 2 diabetes. To further gain insight into the functional differences between the CD9high and CD9low progenitor subsets, we performed transcriptomic profiling of FACS-sorted progenitor populations isolated from oWAT of obese individuals. As CD9low progenitors were markedly decreased in glucose-intolerant or diabetic individuals, we investigated seven women with morbid obesity but without diabetes or glucose intolerance, according to the ADA definition. Overall design: Omental adipose tissue from 7 obese women with mean BMI of 42.9±1.7kg/m2 and mean age of 40.7±3.3 year-old was digested with collagenase. CD9high and CD9low progenitors from the stromal vascular fraction were FACS-sorted with CD45- CD31- CD34+ CD44+ PDGFRa+ CD9high and CD45- CD31- CD34+ CD44+ PDGFRa+ CD9low. Total RNA was amplified and labeled using Ovation Pico WTA System V2 (NuGEN) and Encore BiotinIL Module (NuGEN) kits according to the manufacturer's protocol.
Project description:We profiled gene expression in peripheral blood cells from 17 obese patients by microarray analysis and revealed that visceral fat adiposity impact on gene expression profile in peripheral blood cells compared to subcutaneous fat accumulation. Overall design: Obesity was defined as body mass index (BMI) greater than 25 kg/m2 according to the Japanese criteria. Visceral fat area (VFA) and subcutaneous fat area (SFA) were measured by computed tomography (CT) and determined in the cross-sectional slice at the umbilical level. Subjects with type 1 diabetes mellitus, malignant diseases, autoimmune diseases, and infectious diseases were excluded. Patients treated with anti-diabetic drugs were also excluded.
Project description:Human skeletal muscle was obtained from five individuals: Two hyperglycaemic type 2 diabetics, one diabetic subjects with normal fasting glucose and two healthy control subjects matched for age and BMI.
Project description:Glucocorticoid excess is linked to central obesity, adipose tissue insulin resistance and type 2 diabetes mellitus. The aim of our study was to investigate the effects of dexamethasone on gene expression in human subcutaneous and omental adipose tissue, in order to identify potential novel mechanisms and biomarkers for glucocorticoid-induced insulin resistance in adipose tissue. Dexamethasone changed the expression of 527 genes in both subcutaneous and omental adipose tissue. FKBP5 and CNR1 were the most responsive genes in both depots (~7-fold increase). Dexamethasone increased FKBP5 gene and protein expression in a dose-dependent manner in both depots, but FKBP5 protein levels were 10-fold higher in omental than subcutaneous adipose tissue. FKBP5 gene expression in subcutaneous adipose tissue was positively correlated with serum insulin, HOMA-IR and subcutaneous adipocyte diameter, while fold change in gene expression by dexamethasone was negatively correlated with clinical markers of insulin resistance, i.e. HbA1c, BMI, HOMA-IR and serum insulin. Only one gene, SERTM1, clearly differed in response to dexamethasone between the two depots. Dexamethasone at high concentrations, influences gene expression in both subcutaneous and omental adipose tissue in a similar pattern and promotes gene expression of FKBP5, a gene that may be implicated in glucocorticoid-induced insulin resistance. Paired human subcutaneous (sc) and omental (om) adipose tissue samples obtained from 4 non-diabetic adipose tissue donors (4 M; BMI: 20.8-27.5 Kg/m2) were incubated without (Ctr) or with dexamethasone (Dex, 3 μM) for 24 h.
Project description:This experiment was designed to study if there are differences in gene expression in the adipose tissue of women affected by polycystic ovary syndrome (PCOS) compared to non-hyperandrogenic women. PCOS is the most common endocrinopathy in women of reproductive age, and is characterized by hyperandrogenism and chronic anovulation. This disease is frequently associated with obesity, insulin resistance, and defects in insulin secretion, predisposing these women to type 2 diabetes, atherosclerosis, and cardiovascular disease. We have applied high-density oligonucleotide arrays to omental adipose tissue samples obtained from eight morbidly obese PCOS patients and seven morbidly obese non-PCOS women at the time of bariatric surgery. Keywords: Disease state analysis Overall design: We have compared the omental adipose tissue of eight PCOS patients with the same tissue in seven control women without PCOS. All of them are morbidly obese subjects. We also have included two replicates, one biological and one technical.
Project description:Obesity has considerable effects on morbidity and mortality, and the prevalence of obesity has been increasing rapidly worldwide during the past two decades. Even if obesity affects the entire individual, adipose tissue plays a central role in the development of obesity. Expression profiling of adipose tissue may give insights into the mechanisms contributing to obesity and obesity-related disorders. The Swedish Obese Subjects (SOS) Sib-Pair Study consists of 154 nuclear families with BMI-discordant sib pairs (BMI difference more than 10 kg/m2) resulting in a study population consisting of 732 subjects. The full SOS Sib-Pair study offspring cohort consists of 425 subjects. Microarray expression analysis in subcutaneous adipose tissue was performed in 375 subjects (262 women and 113 men) of the SOS Sib-Pair offspring cohort. Overall design: Microarray expression analysis in subcutaneous adipose tissue was performed in women (n=262) and men (n=113) of the SOS Sib-Pair offspring cohort.
Project description:Obesity has considerable effects on morbidity and mortality, and the prevalence of obesity has been increasing rapidly worldwide during the past two decades. Even if obesity affects the entire individual, adipose tissue plays a central role in the development of obesity. Expression profiling of adipose tissue may give insights into the mechanisms contributing to obesity and obesity-related disorders. The Swedish Obese Subjects (SOS) Sib-Pair Study consists of 154 nuclear families with BMI-discordant sib pairs (BMI difference more than 10 kg/m2) resulting in a study population consisting of 732 subjects. The full SOS Sib-Pair study offspring cohort consists of 425 subjects. Microarray expression analysis in subcutaneous adipose tissue was performed in 375 subjects (262 women and 113 men) of the SOS Sib-Pair offspring cohort. Microarray expression analysis in subcutaneous adipose tissue was performed in women (n=262) and men (n=113) of the SOS Sib-Pair offspring cohort.
Project description:Primary endothelial cells from umbilical cord vein (HUVEC) obtained at delivery from gestational diabetic (GD) women, represent an expedient model for the study of the effects of chronic HG in vivo. In fetal tissues genome-wide epigenetic changes are likely to occur with specific long term and even trans-generational effects. We have utilized this model to study the effects of chronic hyperglycemia on the transcriptome and to verify the presence of specific epigenetic changes associated to chronic HG in vascular cells. HUVEC cells from Umbilical cords of 3 Caucasian Gestational Diabetes women were compared with HUVEC cells from umbilical of from 3 Caucasian non diabetic women matching for age and Body Mass Index. [sample collection] Umbilical cords were obtained from 3 Caucasian Gestational diabetes women (diagnosed not later than 28 th gestational week - gw) and from 3 Caucasian non diabetic women matching for age and Body Mass Index (BMI). All pregnants signed an informed consent. All donors were normotensive, and underwent a 100 g 3 hours Oral Glucose Tolerance Test (OGTT) between the 24 -34th gw. Each woman performed a 7 points-blood glucose monitoring on 3 days at week 34 -36th gw.
Project description:Single-cell RNA-seq (scRNA-seq) of pancreatic islets have reported on α- and β-cell gene expression in mice and subjects of predominantly European ancestry. We aimed to assess these findings in East-Asian islet-cells. 448 islet-cells were captured from three East-Asian non-diabetic subjects for scRNA-seq. Hierarchical clustering using pancreatic cell lineage genes was used to assign cells into cell-types. Differentially expressed transcripts between α- and β-cells were detected using ANOVA and in silico replications of mouse and human islet cell genes were performed. We identified 118 α, 105 β, 6 δ endocrine cells and 47 exocrine cells. Besides INS and GCG, 26 genes showed differential expression between α- and β-cells. 10 genes showed concordant expression as reported in rodents, while FAM46A was significantly discordant. Comparing our East-Asian data with data from primarily European subjects, we replicated several genes implicated in nuclear receptor activations, acute phase response pathway, glutaryl-CoA/tryptophan degradations and EIF2/AMPK/mTOR signaling. Additionally, we identified protein ubiquitination to be associated among East-Asian β-cells. We report on East-Asian α- and β-cell gene signatures and substantiate several genes/pathways. We identify expression signatures in East-Asian β-cells that perhaps reflects increased susceptibility to cell-death and warrants future validations to fully appreciate their role in East-Asian diabetes pathogenesis. Overall design: 448 islet-cells were captured from three East-Asian non-diabetic subjects for scRNA-seq. 223 islet-cells remained after samples QC, and these cells were used for subsequent analyses. Hierarchical clustering using pancreatic cell lineage genes was used to assign cells into cell-types. We identified 118 α and 105 β endocrine cells in our dataset.
Project description:To learn about the etiology of lung cancer among never-smoking women in Asia, we formed the Female Lung Cancer Consortium in Asia (FLCCA), which includes studies of lung cancer in Eastern Asia and conducted a GWAS. We analyzed a total of 5510 lung cancer cases and 4544 controls and identified 3 novel loci (Lan et al., 2012). Of these study subjects, 4922 lung cancer cases and 3959 controls are available for posting. Lan et al.., Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia. Nat Genet. 2012 Dec;44(12):1330-5. doi: 10.1038/ng.2456. Epub 2012 Nov 11. PubMed PMID: 23143601.