Dihydroceramide- and ceramide-profiling provides insights into human cardiometabolic disease etiology

C. Wittenbecher, R. Cuadrat, L. Johnston, F. Eichelmann, Simon Jäger, O. Kuxhaus, M. Prada, F. Del Greco M., A. A. Hicks, P. Hoffman, J. Krumsiek, F. B. Hu and M. B. Schulze ()
Additional contact information
C. Wittenbecher: German Institute of Human Nutrition Potsdam-Rehbruecke
R. Cuadrat: German Institute of Human Nutrition Potsdam-Rehbruecke
L. Johnston: Steno Diabetes Center Aarhus
F. Eichelmann: German Institute of Human Nutrition Potsdam-Rehbruecke
O. Kuxhaus: German Institute of Human Nutrition Potsdam-Rehbruecke
M. Prada: German Institute of Human Nutrition Potsdam-Rehbruecke
F. Del Greco M.: Bolzano/Bozen, Italy, affiliated with the University of Lübeck
A. A. Hicks: Bolzano/Bozen, Italy, affiliated with the University of Lübeck
P. Hoffman: University of Basel
J. Krumsiek: Weill Cornell Medicine
F. B. Hu: Harvard T.H. Chan School of Public Health
M. B. Schulze: German Institute of Human Nutrition Potsdam-Rehbruecke

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract Metabolic alterations precede cardiometabolic disease onset. Here we present ceramide- and dihydroceramide-profiling data from a nested case-cohort (type 2 diabetes [T2D, n = 775]; cardiovascular disease [CVD, n = 551]; random subcohort [n = 1137]) in the prospective EPIC-Potsdam study. We apply the novel NetCoupler-algorithm to link a data-driven (dihydro)ceramide network to T2D and CVD risk. Controlling for confounding by other (dihydro)ceramides, ceramides C18:0 and C22:0 and dihydroceramides C20:0 and C22:2 are associated with higher and ceramide C20:0 and dihydroceramide C26:1 with lower T2D risk. Ceramide C16:0 and dihydroceramide C22:2 are associated with higher CVD risk. Genome-wide association studies and Mendelian randomization analyses support a role of ceramide C22:0 in T2D etiology. Our results also suggest that (dh)ceramides partly mediate the putative adverse effect of high red meat consumption and benefits of coffee consumption on T2D risk. Thus, (dihydro)ceramides may play a critical role in linking genetic predisposition and dietary habits to cardiometabolic disease risk.

Date: 2022
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DOI: 10.1038/s41467-022-28496-1

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