"Regulating the master switch of adipogenesis"

Susanne Mandrup, PhD
Professor, Department of Biochemistry and Molecular Biology,
University of Southern Denmark,
Director of the Center of Excellence in Functional Genomics and Tissue Plasticity and Center for Adipocyte Signaling,
Chair of Biochemistry and Molecular Biology,
Danish Institute of Advanced Study

Adipocytes develop from fibroblastic progenitor cells in the perivascular niche. Using cellular in vitro model systems, we and others have shown that this differentiation is driven by a first wave of transcription factors that induce major chromatin remodeling as well as the expression of the second wave of adipogenic transcription factors that activates the adipocyte gene program. The peroxisome proliferator-activated receptor γ (PPARγ) is the main driver of the second wave and has been shown to be an obligate master regulator of adipogenesis in vitro as well as in vivo. The molecular mechanisms underlying this powerful role of PPARγ are currently not well understood; however, studies in our group indicate that unique chromatin remodeling properties of PPARγ plays a role. Furthermore, our recent work shows that the PPARG locus is associated with a highly interconnected enhancer community that may allow its transcription to be dramatically induced during differentiation.