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Metabolism

In the Metabolism research area, we focus on the interplay between metabolic organs (e.g. adipose tissue and skeletal muscle) and the cardiovascular system under healthy, obese and diabetic circumstances. Four important mediators of this interplay are:1 Hormones, chemokines and cytokines (adipokines, myokines).2 Circulating immune cells. 3 Extracellular vesicles (exosomes).4 Lipids and other metabolites.

Our research

Metabolism research focuses on 3 sub-topics: inflammation, obesity/insulin resistance, and metabolomics/ lipidomics. In the inflammation area, systemic low-grade inflammation as well as local inflammatory processes were studied, as both are key drivers of atherosclerosis, atherothrombosis and atherosclerotic plaque rupture. This work was done in collaboration with, among others, the research area “Proteomics & biomarkers”.

In the obesity/insulin resistance area, the focus has been on adipose tissue (AT) dysfunction, which is a strong driver for insulin resistance, which in turn is strongly associated with CVD. AT dysfunction is associated with alterations in both adipokine secretion and AT-resident immune cells (see key publication). Finally, major technological advances have recently been made in the field of metabolomics/lipidomics, which can now be applied to the field of CVD.
We focus mainly on metabolic signaling and CVD in two disorders: obesity and type II diabetes.  More research will be done on these signals in other patient groups and populations.

Key publications

Schipper, H.S., Rakhshandehroo, M., van de Graaf, S.F.J., Venken, K., Koppen, A., Steinstra, R., Prop, S., Meerding, J., Hamers, N., Besra, G., Boon, L., Nieuwenhuis, E.E.A., Elewaut, D., Prakken, B.J., Kersten, S., Boes, M. and Kalkhoven, E. Natural killer T cells in adipose tissue prevent insulin resistance . J. Clin. Invest. 2012; 122: 3343-54.

Kranendonk, M.E.G., Visseren, F.L.J., van Balkom, B.W., Nolte-’t Hoen, E.N.M., van Herwaarden, J.A., Schipper, H.S., Wauben M.H. and Kalkhoven, E. (2014) Adipocyte-derived extracellular vesicles promote differentiation of monocytes into adipose tissue macrophages. Obesity, in press.

Principal investigators

PIs

Franx, Joles, de Kleijn, Pasterkamp, Visseren, Adan, Biessels, Broekmans, Fauser, van der Graaf, Grobbee, van Haeften, Kappelle, Spiering, de Valk, Visseren, Brenkman, Helms

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