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Updated: May 27, 2026
08:34
Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
Poly(ADP-ribose)polymerase-1 (PARP1) controls adipogenic gene expression and adipocyte function.
Süheda Erener1, Mareike Hesse, Radina Kostadinova
1Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, 8057 Zurich, Switzerland.
Molecular Endocrinology (Baltimore, Md.)
|November 5, 2011
Summary
Poly(ADP-ribose)polymerase-1 (PARP1) regulates adipocyte differentiation by influencing gene expression through histone modifications. PARP1 activation, potentially via DNA breaks, impacts adipogenesis and obesity-related diseases.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Poly(ADP-ribose)polymerase-1 (PARP1) is a chromatin enzyme impacting chromatin compaction.
- Adipocyte differentiation involves dynamic chromatin landscape modulation.
- PARP1's role in adipogenesis and metabolism, particularly in obesity, requires elucidation.
Purpose of the Study:
- To investigate the transcriptional role of PARP1 in adipogenesis and metabolism.
- To elucidate the molecular action of PARP1 in obesity-related diseases using adipocyte models.
Main Methods:
- Studied PARP1-dependent ADP-ribose polymer (PAR) formation during adipocyte development.
- Analyzed PARP1 recruitment to PPARγ2 target genes (e.g., CD36, aP2).
- Assessed changes in histone marks (H3K9me3, H3K4me3) at the PPARγ2 promoter.
- Investigated the effect of a topoisomerase II inhibitor on PARP1 activity.
Main Results:
- PARP1-dependent PAR formation increases during adipocyte development.
- PARP1 sustains PPARγ2 and its target gene expression in late adipogenesis.
- PARP1 is recruited to PPARγ2 target genes in a PAR-dependent manner.
- PARP1 alters histone marks at the PPARγ2 promoter, decreasing repressive marks and increasing activating marks.
- Topoisomerase II inhibition prevents PARP1 activation, suggesting DNA breaks initiate PAR formation.
Conclusions:
- PARP1 is a critical regulator of PPARγ2-dependent gene expression in adipocytes.
- PARP1 influences adipocyte function and has implications for obesity-related diseases.
- PARP1's regulatory function in adipogenesis involves modulating histone marks, potentially triggered by DNA breaks.
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