DNA methylation influencing metabolism and inflammation in adipose tissue

Adipose tissue plays a central role in whole body energy metabolism as an endocrine organ that coordinates energy intake and utilization. This study aims to examine molecular mechanisms underlying T2D using genome wide expression and DNA methylation data in adipose tissue from monozygotic twin pairs.

We first tested if sets of related genes were altered in diabetic versus non diabetic twins, and then tested if expression of individual genes was altered in adipose tissue from diabetic versus non-diabetic twins. We found decreased expression of genes involved in oxidative phosphorylation, carbohydrate, amino acid and lipid metabolism, and increased expression of genes involved in inflammation and glycan degradation.

DNA methylation in humans is influenced by both diet and exercise suggesting that epigenetics could be involved in age and life style related diseases such as T2D. So we analyzed expression of six selected genes in adipose tissue from unrelated subjects with NGT or T2D. Including PPARG, KCNQ1, Tcf7L2 and IRS1 showed differential DNA methylation in adipose tissue from unrelated subjects with T2D compared with controls.

There is an unacceptably high rate of graft failure and delayed engraftment kinetics in adult recipients, for the limited number of stem cell present in a single CB collection, Several strategies are taken, such as the infusion of two different CB grafts or the ex vivo expansion of CB CD34+ cells using a variety of cytokine combinations More recently, mesenchymal cell-feeder layers or a number of molecules have been added to these cytokine combinations.

Firstly, we treated dividing CB CD34+ cells ex vivo with several histone deacetylase inhibitors (HDACIs) and evaluated their ability to increase the numbers of CD34+ cells generated in vitro under SC or SF culture conditions. Treatment of CB CD34+ cells with the most active HDACI, valproic acid (VPA), following an initial 16-hour cytokine priming, increased the number of multipotent cells (CD34+CD90+) generated; however, the degree of expansion was substantially greater in the presence of both VPA and cytokines for a full 7 days.

To summary, we take advantage of the strengths of a twin study design to present for the first time both genome-wide mRNA and DNA methylation profiles in adipose tissue from MZ twin for T2D. This work demonstrates that decreased expression of genes involved in energy metabolism and increased expression of inflammatory genes.

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