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Basic Research in Cardiology

, 113:45 | Cite as

Purinergic receptor Y2 (P2Y2)- dependent VCAM-1 expression promotes immune cell infiltration in metabolic syndrome

  • Julian Merz
  • Philipp Albrecht
  • Sunaina von Garlen
  • Ibrahim Ahmed
  • Daniel Dimanski
  • Dennis Wolf
  • Ingo Hilgendorf
  • Carmen Härdtner
  • Katja Grotius
  • Florian Willecke
  • Timo Heidt
  • Heiko Bugger
  • Natalie Hoppe
  • Ulrich Kintscher
  • Constantin von zur Mühlen
  • Marco Idzko
  • Christoph Bode
  • Andreas Zirlik
  • Peter Stachon
Original Contribution
  • 137 Downloads

Abstract

Sterile inflammation of visceral fat, provoked by dying adipocytes, links the metabolic syndrome to cardiovascular disease. Danger-associated molecular patterns, such as adenosine triphosphate (ATP), are released by activated or dying cells and orchestrate leukocyte infiltration and inflammation via the purinergic receptor P2Y2. The gene expression of ATP receptor P2Y2 did not change in several tissues in the course of obesity, but was increased within epididymal fat. Adipose tissue from P2Y 2 −/− mice consuming high-fat diet (HFD) contained less crown-like structures with a reduced frequency of adipose tissue macrophages (ATMs). This was likely due to decreased leukocyte migration because of missing VCAM-1 exposition on P2Y2 deficient hypertrophic adipose tissue endothelial cells. Accordingly, P2Y 2 −/− mice showed blunted traits of the metabolic syndrome: they gained less weight compared to P2Y 2 +/+ controls, while intake of food and movement behaviour remained unchanged. Liver and adipose tissue were smaller in P2Y 2 −/− animals. Insulin tolerance testing (ITT) performed in obese P2Y 2 −/− mice revealed a better insulin sensitivity as well as lower plasma C-peptide and cholesterol levels. We demonstrate that interfering with somatic P2Y2 signalling prevents excessive immune cell deposition in diet-induced obesity (DIO), both attenuating adipose tissue inflammation and ameliorating the metabolic phenotype. Thus, blocking the P2Y2 cascade may be a promising strategy to limit metabolic disease and its sequelae.

Keywords

Metabolic syndrome Purinergic receptors Immune cell infiltration Find-me signal Inflammation 

Notes

Funding information

This work was supported by a research grant of the German Research Foundation to Peter Stachon and Andreas Zirlik (DFG STA 1446/2-1 and ZI 743/7-1). Philipp Albrecht was supported by a research grant of the German Cardiac Society (DGK). Sunaina von Garlen was supported by a research grant of German Society of Internal Medicine (DGIM).

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to declare.

Supplementary material

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Supplementary material 1 (PNG 292 kb)
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Supplementary material 2 (PNG 296 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Julian Merz
    • 1
    • 2
  • Philipp Albrecht
    • 1
  • Sunaina von Garlen
    • 1
  • Ibrahim Ahmed
    • 1
  • Daniel Dimanski
    • 1
  • Dennis Wolf
    • 1
  • Ingo Hilgendorf
    • 1
  • Carmen Härdtner
    • 1
  • Katja Grotius
    • 1
  • Florian Willecke
    • 1
  • Timo Heidt
    • 1
  • Heiko Bugger
    • 1
  • Natalie Hoppe
    • 1
  • Ulrich Kintscher
    • 3
  • Constantin von zur Mühlen
    • 1
  • Marco Idzko
    • 4
  • Christoph Bode
    • 1
  • Andreas Zirlik
    • 1
    • 5
  • Peter Stachon
    • 1
  1. 1.Department of Cardiology and Angiology I, University Heart Center Freiburg, Faculty of MedicineUniversity of FreiburgFreiburgGermany
  2. 2.Faculty of BiologyUniversity of FreiburgFreiburgGermany
  3. 3.Center for Cardiovascular Research, Institute of PharmacologyCharité Universitaetsmedizin BerlinBerlinGermany
  4. 4.Department of PneumologyMedical University of ViennaViennaAustria
  5. 5.Department of CardiologyMedical University of GrazGrazAustria

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