Development of Compact Fat Graft by Modulating PPARγ Neddylation
Il-Kug Kim1, Uk-Il Ju2, Ki Yong Hong3, Ung Sik Jin4, Yang-Sook Chun2, Hak Chang4.
1Department of Plastic and Reconstructive Surgery, Yeungnam University College of Medicine, Daegu, Korea, Republic of, 2Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea, Republic of, 3Department of Plastic and Reconstructive Surgery, Dongguk University Medical Center, Seoul, Korea, Republic of, 4Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine, Seoul, Korea, Republic of.
Purpose: Adipogenesis is regulated by nuclear hormone receptors such as PPARγ and C/EBPα. The expressions of PPARγ and C/EBPα are maintained in mature adipocytes and induce lipid accumulation and adipokine secretion. PPARγ neddylation by NEDD8 is essential in this process. We investigated the effect of PPARγ neddylation inhibitor, MLN4924 in fat graft survival and its mechanism.
Methods: From wild type C57BL/6J mice, subcutaneous fat was harvested and chopped into small pieces. DMSO (control), MLN4924 0.25 μM, 0.5 μM were treated to harvested fat tissue for 4 days. Then fat injection into a recipient mouse at the supraperiosteal plane of skull was performed. Transferred fat volume analysis, H&E, immunohistochemistry for F4/80, CD206, pimonidazole were done 4, 8 weeks after fat graft.
Results: The size of adipocytes were decreased with MLN4924 treatment. The volume of transferred fat was larger in MLN4924 treated group compared to control. Tissue hypoxia was decreased and M2 macrophages were increased in MLN4924 treated group compared to control.
Conclusions: Compact fat graft by inhibition of PPARγ neddylation ameliorates transferred adipose tissue survival through improvement of microenvironment including hypoxia and macrophage polarization.
Figure 1. MLN4924 reduces the size of adipocytes in adipose tissues.
Figure 2. Improved fat graft survival with MLN4924 treatment.
Figure 3. M2 polarity of macrophages was increased in MLN4924 treated group.
Figure 4. Hypoxic status was improved in MLN4924 treated group.
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