RESEARCH ARTICLE Characterization of Dedifferentiating Human Mature Adipocytes from the Visceral and Subcutaneous Fat Compartments: Fibroblast- Activation Protein Alpha and Dipeptidyl Peptidase 4 as Major Components of Matrix Remodeling

Mature adipocytes can reverse their phenotype to become fibroblast-like cells. This is achieved by ceiling culture and the resulting cells, called dedifferentiated fat (DFAT) cells, are multipotent. Beyond the potential value of these cells for regenerative medicine, the dedifferentiation process itself raises many questions about cellular plasticity and the path-ways implicated in cell behavior. This work has been performed with the objective of obtain-ing new information on adipocyte dedifferentiation, especially pertaining to new targets that may be involved in cellular fate changes. To do so, omental and subcutaneous mature adi-pocytes sampled from severely obese subjects have been dedifferentiated by ceiling cul-ture. An experimental design with various time points along the dedifferentiation process has been utilized to better understand this process. Cell size, gene and protein expression as well as cytokine secretion were investigated. Il-6, IL-8, SerpinE1 and VEGF secretion were increased during dedifferentiation, whereas MIF-1 secretion was transiently in-creased. A marked decrease in expression of mature adipocyte transcripts (PPARγ2, C/ EBPα, LPL and Adiponectin) was detected early in the process. In addition, some matrix re