Forschungsprojekte (Drittmittel)

Projekt

Aging and Metabolic Programming

Ageing is associated with increased risks of various chronic diseases. The Helmholtz Alliance AMPro is seeking to find new preventive and therapeutic measures contributing to healthy  metabolic processes. We develop mathematical models describing inter-organ interactions on one hand, and investigate the metabolic effects of various food supplementations or compositions on the other. Together with Karsten Hiller (Technische Universität Braunschweig), we have analyzed the metabolic effects of guar gum and chickpea flour as food supplementation by a network modeling approach. The 13C-labeled flour was ingested by healthy subjects, various metabolites were measured in a gas chromatography/mass spectrometry based metabolomics approach, which were then analyzed by our modeling approach. It was known before that those foods are able to attenuate postprandial hyperglycemia. By modeling the kinetics of the key metabolites involved in glycolysis and the TCA cycle from control and intervention groups, we detected that the food supplements have additional glucose-independent effects for downstream metabolites, especially pyruvate. In a follow-up study, we found that the additional proteins in wheat, in contrast to pure glucose, have time-dependent effects on the same metabolic network. In two hours after eating, the effect of the additional proteins manifests in the conversion of pyruvate to citrate. After that, the effect shifts to the conversion between pryuvate and alanine. The time-dependent effects found in this project are consistent with the findings generated in an independent study of hepatic insulin signaling recently performed by our group. By using a combination of state-of-the-art metabolomics and mathematical modeling, our models elucidate the effect of food composition on downstream metabolism, helping in the design of novel food supplements and interventions to counter the effects of ageing and chronic disease on metabolism.

Simm members

Arnab Barua, Michael Meyer-Hermann

HZI collaborators

Dagmar Wirth, Ingo Schmitz

other collaborators

Karsten Hiller (Technische Universität Braunschweig)

Publications

Schlicker L, Boers HM, Dudek C-A, Zhao G, Barua A, Trezzi J-P, Meyer-Hermann M, Jacobs DM, Hiller K. Postprandial metabolic effects of fiber mixes revealed by in vivo stable isotype labelling in human. Metabolites (2019) May 7; 9(5): E91.

Zhao G, Wirth D, Schmitz I, Meyer-Hermann M. A mathematical model of the impact of insulin secretion dynamics on selective hepatic insulin resistance. Nature Commun 8 (2017) 1362.
 

 

Projektleiter

Beteiligte Gruppen

Geldgeber / Förderer

Helmholtz

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