Ricerc@Sapienza

Increased consumption of calorie-dense foods is leading to an epidemic of cardiometabolic conditions including diabetes and cardiovascular disease. Solid evidence exists that postprandial abnormal increases in blood glucose cause oxidative stress, inflammation and proatherogenic changes. Consistently, post-challenge glucose level is an independent predictor of future cardiovascular events even in normoglycemic individuals. However, the molecular mechanisms underlying the link between postprandial glucose spikes with oxidative stress and proinflammatory/atherogenic changes remain elusive. Carbonyl stress is characterized by an increase in the steady-state levels of reactive carbonyl species (RCS). These glycotoxins are generated as intermediates of glucose metabolism. Glycolysis-derived RCS include the ¿-dicarbonyl compounds 3-deoxyglucosone, methylglyoxal, and glyoxal. By reacting with proteins, RCS lead to formation of advanced glycation endproducts (AGEs), including N¿-(carboxyethyl)lysine, and N¿-(carboxymethyl)lysine. In turn, AGEs are recognized by receptors of the innate immune system, particularly the receptor for AGEs (RAGE), leading to reactive oxygen species formation and inducing a chronic inflammatory response. The purpose of this project is to investigate whether (1) glycolysis-derived RCS and the corresponding AGE structures are increased after an oral glucose challenge in young (25-40 years), lean (BMI