Fatty acid metabolism and cardiometabolic diseases

Contact persons: Dr. Fabian Eichelmann, Marcela Prada

We are investigating the role of fatty acids for the incidence of type 2 diabetes and cardiovascular diseases using biochemical markers and gene analyses in the EPIC-Potsdam study. We observed strong associations for n-6 polyunsaturated fatty acids (n-6 PUFA), among others. In order to identify biological mechanisms of these associations, the focus was on the delta-5- and delta-6-desaturases. These are enzymes involved in PUFA metabolism. That PUFA metabolism is relevant to diabetes risk is further supported by an approach in which we were able to find genetic determinants for diabetes-associated fatty acids and lipid metabolites. In addition, we are generating data-based hypotheses on metabolic pathways linking food consumption to diabetes risk. For example, our analyses support that specific phosphatidylcholines, sphingomyelins, and ceramides are potential mediators of the relationship between red meat and type 2 diabetes.

Although we observed that fatty acid concentrations in phospholipids and certain serum lipid metabolites are associated with risk of type 2 diabetes, the role of fatty acid composition within lipid classes on cardiometabolic disease remained unclear. Therefore, lipidomics profiles are investigated in the EPIC-Potsdam study with regard to diabetes as well as cardiovascular disease risk. The lipidomics platform used allows both the quantification of lipid metabolites and the determination of their fatty acid composition in different lipid classes. First results indicate that many individual lipids show statistical associations with either a higher or lower risk. In cooperation with partners of the consortium FAME (Fatty Acid Metabolism - Interlinking Diet with Cardiometabolic Health), which we coordinated, it was subsequently shown that a large number of those lipids could be positively influenced by exchanging saturated for unsaturated fatty acids in the diet. The EPIC-Potsdam study also generated extensive genetic and epigenetic data. This allows us to identify determinants of fatty acid metabolism that alter the effect of the diet.

In addition, we are specifically interested in biomarkers of dairy fat consumption and their association with disease risk. Odd-numbered saturated fatty acids determined by lipidomics showed different distribution patterns across lipid classes and were associated with diabetes risk depending on the lipid class. In our laboratory, we also measured trans fatty acids in blood samples from EPIC-Potsdam participants, including several fatty acids characteristic of milk fat. The results suggest that the isomers of trans fatty acids from milk fat have different relationships with T2D risk.

Individual Projects

• Gene-environment interactions to identify subgroups with different dietary responses, DZD – BMBF/State of Brandenburg
• Epigenetic markers as risk markers for type 2 diabetes, DZD – BMBF/ State of Brandenburg