PARP-1 suppresses adiponectin expression through poly(ADP-ribosyl)ation of PPARγ in cardiac fibroblasts

Aims: Our aim was to explore the mechanism underlying the transcriptional regulation of adiponectin and its receptors (AdipoR) in cultured rat cardiac fibroblasts. Methods and results: Using western blot and real-time RT-PCR assays, the expression of adiponectin and its receptors was determined. Using Southwestern blot and electrophoretic mobility shift assays, the DNA binding activity of peroxisome proliferator activated receptor γ (PPARγ) was determined. The results showed that adiponectin and AdipoR1 were highly expressed in cultured rat cardiac fibroblasts. Inhibition of poly(ADP-ribose) polymerase 1 (PARP-1) by 3-aminobenzamide, PJ34, or PARP-1 siRNA markedly increased the transcription of adiponectin and AdipoR1 in cultured fibroblasts, mature 3T3 L1 adipocytes, rat myocardium, and white adipose tissue. PPARγ was poly(ADP-ribosyl)ated by PARP-1 in cardiac fibroblasts under basal conditions. Poly(ADP-ribosyl)ation of PPARγ prevented its binding to DNA. Inhibition of PARP-1 enhanced the DNA binding and transactivation of PPARγ and increased the transcription of PPARγ-target genes including CD36, lipoprotein lipase, and leptin in cultured fibroblasts. Conclusion: PARP-1 inhibits adiponectin and AdipoR1 expression as well as PPARγ transactivation through poly(ADP-ribosyl)ation of PPARγ in cultured rat cardiac fibroblasts.