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Suppression of cardiac phosphatidate phosphohydrolase 1 activity and lipin mRNA expression in Zucker diabetic fatty rats and humans with type 2 diabetes mellitus

Christof Burgdorf*, Laura Hänsel, Marc Heidbreder, Olaf Jöhren, Frank Schütte, Heribert Schunkert, Thomas Kurz

*Corresponding author for this work

Abstract

Lipin functions in mammalian phospholipid biosynthesis through its phosphatidate phosphohydrolase 1 (PAP1) activity. Here, we studied cardiac PAP1 activity and lipin expression ex vivo in 8-month-old Zucker diabetic fatty (ZDF) rats and humans with type 2 diabetes mellitus undergoing open heart surgery for coronary bypass grafting. Compared to non-diabetic littermates (ZDF-fa/+), left ventricular PAP1 activity was 29% lower in diabetic ZDF-fa/fa rats. Left ventricular PAP1 activities were 2.1-fold (ZDF-fa/fa) and 3.6-fold (ZDF-fa/+) higher than the respective atrial activities, indicating marked differences in cardiac distribution of PAP1. PAP1 activity was highly related with cardiac lipin-1 and lipin-3 mRNA expression in ZDF rats (r = 0.99 and 0.96). Consistent with the findings in experimental animals, human atrial tissue displayed PAP1 activity that was 33% lower in those having diabetes than in non-diabetic controls. Accordingly, atrial lipin-1 and lipin-3 mRNA expression in diabetic patients was 50% and 59% lower as in non-diabetic patients, respectively. Insulin therapy increased both PAP1 activity and lipin mRNA expression in diabetic patients. We conclude that suppression of cardiac PAP1 activity/lipin expression may contribute to metabolic dysfunction of the diabetic heart.

Original languageEnglish
JournalBiochemical and Biophysical Research Communications
Volume390
Issue number1
Pages (from-to)165-170
Number of pages6
ISSN0006-291X
DOIs
Publication statusPublished - 04.12.2009

Funding

This study was supported by a grant of the Faculty of Medicine at the University of Lübeck (Forschungsförderung A40-2005 and E29-2009 ). We are very grateful to Ines Stölting, Anke Constanz, and Christine Eichholz for their technical assistance and to the team from the Department of Cardiac Surgery, University Hospital Schleswig-Holstein, Campus Lübeck, for cooperation in supplying atrial appendages from open heart surgery. Appendix A

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

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