Metabolomics in dietary interventions: Special emphasis on effects of grain products and fish on lipidomic profile: Dissertation

Metabolic syndrome (MetS) increases markedly the risk for type 2 diabetes mellitus (T2DM), but in contrast to advanced T2DM, MetS and pre-stages of T2DM may be reversible conditions, if addressed early enough by lifestyle modifications. Based on epidemiological evidence, whole grain foods, fatty fish and polyphenol rich fruits and vegetables, including berries, may help prevent the development of T2DM and cardiovascular diseases (CVD), but evidence from clinical trials is not incontestable. Metabolomics and lipidomics allow characterization of the effects of diet in more detail than more conventional approaches in nutrition research and could therefore help elucidate the
complex relationship between nutrition and metabolism. The overall aim of this work was to study the effects of whole grain, low insulin response grain products and rye, fish, and bilberries in subjects at increased risk for MetS or CVD by applying metabolomics approaches, with specific emphasis on the characterization of molecular lipids by lipidomic approaches. The intake of whole grain or rye over a period of 12 weeks did not change lipidomic
profiles. In contrast, a diet rich in oat-wheat bread and potato in the same study increased proinflammatory lysophosphatidylcholines. Consumption of high-fiber rye bread over a period of 8 weeks increased specific plasma metabolites that might mediate positive effects of rye bread on satiety and weight maintenance. In another study, the consumption of fatty fish decreased ceramides and diacylglycerols which are potential mediators of lipid induced insulin resistance and inflammation. In a 12-week intervention study, diet rich in whole grain and low insulin response grain products, fatty fish and bilberries altered lipidomic
profile especially increasing triacylglycerols with long chain (n-3) polyunsaturated fatty acids. Increases in eicosapentaenoic acid and docosahexaenoic acid were associated with improved insulin secretion and glucose disposal. In conclusion, this thesis indicated that metabolomics is a valuable tool for studying effects of dietary interventions at the molecular level. Dietary changes altered metabolic profiles, e.g. altering lipids related to peroxidation, inflammation and insulin signaling, which may further affect predisposition to T2DM and CVD in high-risk persons.