Project description:The aim of this study was to identify new genes controlling insulin sensitivity in adipocytes from obese women with either insulin-resistant (OIR) or -sensitive (OIS) adipocytes. 432 genes were differentially expressed between the OIR and OIS group (FDR <5%). These genes are enriched in pathways related to glucose and amino acid metabolism, cellular respiration, and insulin signaling. Two IR-associated genes, KLF15 and SLC25A10, were selected for functional evaluation.
Project description:The aim of this study was to identify new genes controlling insulin sensitivity in adipocytes from obese women with either insulin-resistant (OIR) or -sensitive (OIS) adipocytes. 432 genes were differentially expressed between the OIR and OIS group (FDR <5%). These genes are enriched in pathways related to glucose and amino acid metabolism, cellular respiration, and insulin signaling, and include SLC2A4, AKT2, as well as enzymes in the mitochondria respiratory chain. Two IR-associated genes, KLF15 and SLC25A10, were selected for functional evaluation.
Project description:The association between central obesity and insulin resistance reflects the properties of visceral adipose tissue. Our aim was to gain further insight into this association by analysing the lipid composition of subcutaneous and omental adipose tissue in obese women with and without insulin resistance. Subcutaneous and omental adipose tissue and serum were obtained from 29 obese nondiabetic women, 13 of whom were hyperinsulinemic. Histology, and lipid and gene profiling were performed. In omental adipose tissue of obese, insulin-resistant women, adipocyte hypertrophy and macrophage infiltration were accompanied by an increase in GM3 ganglioside and its synthesis enzyme ST3GAL5; in addition, phosphatidylethanolamine (PE) lipids were increased and their degradation enzyme, PEMT, decreased. ST3GAL5 was expressed predominantly in adipose stromovascular cells and PEMT in adipocytes. Insulin resistance was also associated with an increase in PE lipids in serum. Total RNA was isolated and up to 400 ng of total RNA per sample was labelled and hybridized to Illumina HumanHT-12_V4 expression BeadChip platform. Paired subcutaneous and omental samples from 6 women were analysed.
Project description:The association between central obesity and insulin resistance reflects the properties of visceral adipose tissue. Our aim was to gain further insight into this association by analysing the lipid composition of subcutaneous and omental adipose tissue in obese women with and without insulin resistance. Subcutaneous and omental adipose tissue and serum were obtained from 29 obese nondiabetic women, 13 of whom were hyperinsulinemic. Histology, and lipid and gene profiling were performed. In omental adipose tissue of obese, insulin-resistant women, adipocyte hypertrophy and macrophage infiltration were accompanied by an increase in GM3 ganglioside and its synthesis enzyme ST3GAL5; in addition, phosphatidylethanolamine (PE) lipids were increased and their degradation enzyme, PEMT, decreased. ST3GAL5 was expressed predominantly in adipose stromovascular cells and PEMT in adipocytes. Insulin resistance was also associated with an increase in PE lipids in serum.
Project description:Purpose: To determine how STAT1 activity in white adipocytes affects insulin sensitivity. Methods: Adipocyte specific (ADIPOQ-Cre) STAT1 fl/fl mice (STAT1 fKO) and littermate controls (STAT1 fl/fl) were placed on 60% HFD for 18 weeks, followed by metabolic phenoptying and tissue harvest for RNA-seq Results: STAT1 expression in WAT inversely correlated with fasting plasma glucose in both obese mice and humans. Metabolomic and gene expression profiling established STAT1 deletion in adipocytes (STAT1 fKO) enhanced mitochondrial function and accelerated TCA cycle flux coupled with subcutaneous WAT hyperplasia. STAT1 fKO reduced WAT inflammation, but insulin resistance persisted in obese mice. Rather, elimination of type I cytokine interferon gamma (IFNg) activity enhanced insulin sensitivity in diet-induced obesity. Conclusions: Our findings reveal a permissive mechanism that bridges WAT inflammation to whole-body insulin sensitivity.
Project description:Maternal obesity in pregnancy is associated with increased birth-weight, obesity and premature mortality in adult offspring. The Effect of Metformin on Maternal and Fetal Outcomes in Pregnant Obese Women (EMPOWaR) trial was a randomised, double-blind, placebo-controlled trial carried out to determine whether exposure to Metformin would affect the offspring birth-weight centile. Obese women exposed to Metformin had increased insulin sensitivity at 36 weeks of pregnancy, but there were no differences in offspring birthweight. We obtained the placentas from these women to determine whether there were differences in expression of genes regulating fetal growth and metabolism. In a complementary study we investigated DNA methylation in the same samples.
Project description:Maternal obesity in pregnancy is associated with increased birth-weight, obesity and premature mortality in adult offspring. The Effect of Metformin on Maternal and Fetal Outcomes in Pregnant Obese Women (EMPOWaR) trial was a randomised, double-blind, placebo-controlled trial carried out to determine whether exposure to Metformin would affect the offspring birth-weight centile. Obese women exposed to Metformin had increased insulin sensitivity at 36 weeks of pregnancy, but there were no differences in offspring birthweight. We obtained the placentas from these women to determine whether there were differences in DNA methylation of genes regulating fetal growth and metabolism. In a related study we investigated the gene expression in the same samples.
Project description:Adipose tissue is an active producer of lactate. In obesity, the increased size of adipocytes is accompanied by an increase in lactate production in adipose tissue, caused by hypoxia in obese adipocytes. How lactate affects metabolism in adipocyte and insulin sensitivity remains unclear. Here we develop a mouse model of MCT1,coding by Slc16a1, specific deletion in adipose tissues, using the AP2 promoter to drive Cre expression. This MCT1 AKO mice develop more severe insulin resistance in obesity with 16 weeks high fat diet treatment, while few changes happen to lipid metabolism in adipose tissues. We used RNA-seq to analyze the gene expression patterns of eWAT of obese MCT1 AKO mice compared to WT, and found significant changes in innate immune signaling and adipocyte apoptosis that reflect systemic inflammation and insulin resistance.