Diabetologie und Stoffwechsel 2021; 16(S 01): S36
DOI: 10.1055/s-0041-1727386
04. Grundlagenforschung Adipositas/Metabolisches Syndrom

Role of microbial Agmatine in metabolic inflammation in humans

L Henneke
1   UKSH Kiel, University of Kiel, Germany, Schleswig-Holstein Exzellenz Lehrstuhl für Innere Medizin Endokrinologie, Diabetologie und klinische Ernährungsmedizin, Kiel, Germany
,
K Schlicht
1   UKSH Kiel, University of Kiel, Germany, Schleswig-Holstein Exzellenz Lehrstuhl für Innere Medizin Endokrinologie, Diabetologie und klinische Ernährungsmedizin, Kiel, Germany
,
T Demetrowitsch
2   Institut für Humanernährung und Lebensmittelkunde, University of Kiel, Germany, Abteilung Lebensmitteltechnologie, Kiel, Germany
,
E Ubbelohde
1   UKSH Kiel, University of Kiel, Germany, Schleswig-Holstein Exzellenz Lehrstuhl für Innere Medizin Endokrinologie, Diabetologie und klinische Ernährungsmedizin, Kiel, Germany
,
T Bruns
1   UKSH Kiel, University of Kiel, Germany, Schleswig-Holstein Exzellenz Lehrstuhl für Innere Medizin Endokrinologie, Diabetologie und klinische Ernährungsmedizin, Kiel, Germany
,
K Hartmann
1   UKSH Kiel, University of Kiel, Germany, Schleswig-Holstein Exzellenz Lehrstuhl für Innere Medizin Endokrinologie, Diabetologie und klinische Ernährungsmedizin, Kiel, Germany
,
K Schwarz
2   Institut für Humanernährung und Lebensmittelkunde, University of Kiel, Germany, Abteilung Lebensmitteltechnologie, Kiel, Germany
,
M Laudes
1   UKSH Kiel, University of Kiel, Germany, Schleswig-Holstein Exzellenz Lehrstuhl für Innere Medizin Endokrinologie, Diabetologie und klinische Ernährungsmedizin, Kiel, Germany
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Background Recently, it was suggested that microbially produced agmatine mediates the advantageous effects of metformin on metabolism and lifespan. Additionally, our data of 1.258 human showed that agmatine production was significantly elevated in metformin-treated T2 D patients compared to untreated T2 D patients.

Methods Firstly, we determined agmatine through semi-targeted metabolomics (FT-ICR-MS) and secondly, we statistically modelled either positive counts or absence / presence of agmatine regarding metabolic and inflammatory parameters in 1.704 subjects of the FoCus cohort (two-part Hurdle model). Further, we aim to investigate agmatine in relation to human cell lines such as THP-1, Hep-G2, CaCo2 and 3T3-L1.

Results Thus far, modelling positive counts of agmatine showed an increased level of agmatine in subjects with elevated Body Mass Index (P = 3.33e-4), elevated waist (P = 2.15e-4) and elevated C-reactive protein (P = 3.56e-2) (linear model). Women with a BMI greater 25 kg / m2 had an increased level of agmatine compared to a BMI lower 25 kg / m2 (P = 8.47e-5). In cell culture we found in macrophages added up to 1 mM of agmatine for 24 h, that cells remained viable up to 92 %. Concentrations from 5 mM decreased viability to 52 %. NF-kB expression was decreased in macrophages added 1 mM of agmatine compared to PBS-controls (0,5 h, 2 h incubation) (n.s.).

Conclusion Our results so far suggest anti-inflammatory effects of agmatine and a positive association with obesity. It indicates that the gut microbiome tries to counteract human metabolic inflammation by producing anti-inflammatory metabolites from beneficial gut bacteria suggesting a symbiotic host-microbe interchange.



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Artikel online veröffentlicht:
06. Mai 2021

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