|Partner Organization||Partner Country|
|Institute of Food Chemistry, TU Dresden||Germany|
|Section of Nutrition and Metabolism, IARC, Lyon||France|
1. Overall project description
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.
For WP1 on the dietary MGO: in vitro and in vivo studies, A two-step static digestion model consisting of a stomach stage (pH 2) and an intestinal stage (pH 7.5) was established. The degradation of MGO was monitored via RP-HPLC and the formation of the reaction products MG-HCr, MG-H1 and CEL was analyzed via LC-QQQ-MS. While only minor amounts of lysine reacted with MGO, both creatine and arginine degraded MGO rapidly. After the intestinal stage, in experiments with creatine 70-90% of MGO had reacted to form MG-HCr and in experiments with arginine 3-5% of MGO had reacted to form MG-H1. Additionally, a small human intervention study, where participants consumed MGO rich Manuka honey simultaneously or separately was conducted to observe formation of MGO-derived MRPs during human digestion. Those samples are currently analyzed. Furthermore, TIM 1 (TNO Gastro-intestinal Model), a dynamic multi-compartmental computer-controlled digestion model was used to study the digestion of MGO. It features continuous chyme transport, dynamic pH regulation and membranes to simulate nutrient absorption to realistically simulate conditions in the lumen. In digestion experiments with only MGO, ca. 23% of MGO was degraded during the stomach stage, ca. 23% of MGO was available for absorption during the small intestinal stage and ca. 13% of MGO was found in the ileal efflux. Further experiments using this model are currently planned.
For WP2 on the dietary MGO and physiological consequences in mice, where mice were subjected to MGO via drinking water, we found significantly increased plasma levels of MGO (1.6 fold), CEL (1.2 fold) and MG-H1 (1.3 fold), but not for CML in these mice compared to the control. Furthermore, we found a significantly increased systolic blood pressure but no changes in vasoreactivity measure by myography in 4 different vascular beds including; saphenous and mesenteric arteries (small) and carotid and femoral arteries (large), as well as vascular stiffness and insulin-induced vasoreactivity. Furthermore, a wide range of tissues including the heart, kidney, brain, fat depots and liver were collected directly after sacrificing the animals for the detection of MGO accumulation or MGO-derived AGEs including the neoformation later on. We are now preparing to repeat these experiments with a dietary-relevant MGO concentration based on a recent publication by our group and synthesized highly purified MGO for this experiment.
For WP3 on dietary MGO and its consequences in humans using existing data and resources from large-scale international prospective cohort studies, first steps were made to develop consumption data for dietary toxic dicarbonyls for the EPIC and Maastricht Study cohorts. This task matches the detailed Schalwijk food dicarbonyl composition database (currently the largest, most detailed database of its kind) to the individual dietary intake data from these cohorts.To implement this task, a virtual meeting of the nutritionists, dietary database experts and epidemiologists involved in the task was convened to identify a common strategy for implementing this task in both cohorts. A strategy was agreed upon and is being implemented, including additional minor food composition analyses for updated data on some common foods consumed by participants in both cohorts. The work on this task is currently on-going and is anticipated to be concluded by the first quarter of 2021 after which the other related WP3 tasks can then commence.
4.1 List of publications
|Authors||Title||Year, Issue, PP||Partners Number||Doi|
|Maasen K, Scheijen JLJM*, Opperhuizen A, Stehouwer CDA, Van Greevenbroek MM, Schalkwijk CG*||Quantification of dicarbonyl compounds in commonly consumed foods and drinks; presentation of a food composition database for dicarbonyls.||2021||10.1016/j.foodchem.2020.128063 + 10.1016/j.foodchem.2020.128578 (acknowledgement JPI-HDHL )||Download|
|Maasen K, Scheijen JLJM*, Opperhuizen A, Stehouwer CDA, Van Greevenbroek MM, Schalkwijk CG*||Corrigendum to “Quantification of dicarbonyl compounds in commonly consumed foods and drinks; presentation of a food composition database for dicarbonyls” [Food Chemistry, 339 (2020) 128063]||2021||10.1016/j.foodchem.2020.128578||Download|
4.2 Presentation of the project
|Target group||Authors||Means of communication||Hyperlink|
4.3 List of submitted patents and other outputs
|Patent licence||Partners involved||Year||International eu or national patent||Comment|