Modeling the Effect of High Calorie Diet on the Interplay between Adipose Tissue, Inflammation, and Diabetes.

BACKGROUND: Type 2 diabetes (T2D) is a chronic metabolic disease potentially leading to serious widespread tissue damage. Human organism develops T2D when the glucose-insulin control is broken for reasons that are not fully understood but have been demonstrated to be linked to the emergence of a chronic inflammation. Indeed such low-level chronic inflammation affects the pancreatic production of insulin and triggers the development of insulin resistance, eventually leading to an impaired control of the blood glucose concentration. On the contrary, it is well-known that obesity and inflammation are strongly correlated. AIM: In this study, we investigate in silico the effect of overfeeding on the adipose tissue and the consequent set up of an inflammatory state. We model the emergence of the inflammation as the result of adipose mass increase which, in turn, is a direct consequence of a prolonged excess of high calorie intake. RESULTS: The model reproduces the fat accumulation due to excessive caloric intake observed in two clinical studies. Moreover, while showing consistent weight gains over long periods of time, it reveals a drift of the macrophage population toward the proinflammatory phenotype, thus confirming its association with fatness.

Transcriptome analysis of human primary endothelial cells (HUVEC) from umbilical cords of gestational diabetic mothers reveals candidate sites for an epigenetic modulation of specific gene expression.

Within the complex pathological picture associated to diabetes, high glucose (HG) has "per se" effects on cells and tissues that involve epigenetic reprogramming of gene expression. In fetal tissues, epigenetic changes occur genome-wide and are believed to induce specific long term effects. Human umbilical vein endothelial cells (HUVEC) obtained at delivery from gestational diabetic women were used to study the transcriptomic effects of chronic hyperglycemia in fetal vascular cells using Affymetrix microarrays. In spite of the small number of samples analyzed (n=6), genes related to insulin sensing and extracellular matrix reorganization were found significantly affected by HG. Quantitative PCR analysis of gene promoters identified a significant differential DNA methylation in TGFB2. Use of Ea.hy926 endothelial cells confirms data on HUVEC. Our study corroborates recent evidences suggesting that epigenetic reprogramming of gene expression occurs with persistent HG and provides a background for future investigations addressing genomic consequences of chronic HG.