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

• Published in: Biochemical and biophysical research communications Vol. 390; no. 1; pp. 165 - 170
• Main Authors: Burgdorf, Christof, Hänsel, Laura, Heidbreder, Marc, Jöhren, Olaf, Schütte, Frank, Schunkert, Heribert, Kurz, Thomas
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.12.2009
• Subjects: Animals; Diabetes mellitus; Diabetes Mellitus, Type 2 - enzymology; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - therapy; Heart Atria - enzymology; Heart Atria - metabolism; Heart Ventricles - enzymology; Heart Ventricles - metabolism; Human atrial tissue; Humans; Insulin - therapeutic use; Lipin; Male; Myocardium - enzymology; Myocardium - metabolism; Nuclear Proteins - biosynthesis; Nuclear Proteins - genetics; Pancreatitis-Associated Proteins; Phosphatidate Phosphatase - metabolism; Phosphatidate phosphohydrolase 1; Phospholipid biosynthesis; Rats; Rats, Zucker; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Zucker diabetic fatty rats; Lipin; Zucker diabetic fatty rats; Human atrial tissue; Phospholipid biosynthesis; Diabetes mellitus; Phosphatidate phosphohydrolase 1
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2009.09.108

Lipin functions in mammalian phospholipid biosynthesis through its phosphatidate phosphohydrolase 1 (PAP 1) activity. Here, we studied cardiac PAP 1 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 PAP 1 activity was 29% lower in diabetic ZDF- fa/fa rats. Left ventricular PAP 1 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 PAP 1. PAP 1 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 PAP 1 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 PAP 1 activity and lipin mRNA expression in diabetic patients. We conclude that suppression of cardiac PAP 1 activity/lipin expression may contribute to metabolic dysfunction of the diabetic heart.