Bioactive compounds produced during food processing can have strong pro-inflammatory properties with potential health implications. Modulation of chronic inflammation may be the mechanism linking diet to risk of chronic diseases such as diabetes and CVD. Advanced glycation endproducts (AGEs) are a heterogeneous group of pro-inflammatory bioactive compounds produced via Maillard reactions during cooking and processing. It is now well established that AGEs are mainly formed from several dicarbonyl compounds, including methylglyoxal (MGO), glyoxal (GO) and 3-deoxyglucosone (3-DG). The glycation activity of these biologically reactive dicarbonyl compounds is much higher as compared to that of sugars, with MGO as the most reactive precursor in the formation of AGEs. We have recently found high levels of MGO in many different foods. There is increasing evidence that elevated levels of MGO are involved in weight gain and the development of diabetes and other chronic inflammatory diseases including cardiovascular disease. However, bioavailability and physiological consequences of dietary MGO are largely unknown. Our aim is to explore the consequences of dietary MGO on the intestinal microbiota and on the development of metabolic diseases.
We will determine the effect of dietary MGO on the gastrointestinal tract and microbiota (WP1) and on the onset of diabetes, vascular diseases and cognitive function in mice (WP2). We will develop a detailed database of dietary MGO exposures and assess the association of dietary MGO with overweight, weight gain, obesity and risk of associated metabolic diseases (type 2 diabetes, CVD), as well as cognitive function using existing data from 3 large and deep-phenotyping prospective cohort studies (WP3). In WP3, we will also investigate the role of inflammation, endothelial function and micro- and macrovascular function and microbiota composition as potential underlying mechanisms of dietary MGO action.
This comprehensive project will elucidate the role of food-derived MGO as a possible risk factor for overweight and overweight-related metabolic diseases.