title: 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.
abstract: 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 pathways implicated in cell behavior. This work has been performed with the objective of obtaining 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 adipocytes sampled from severely obese subjects have been dedifferentiated by ceiling culture. 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 increased. 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 remodeling transcripts (FAP, DPP4, MMP1 and TGFβ1) were rapidly and strongly up-regulated. FAP and DPP4 proteins were simultaneously induced in dedifferentiating mature adipocytes supporting a potential role for these enzymes in adipose tissue remodeling and cell plasticity.
authors: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, Canada.
authors: Julie
authors: J
authors: Lessard
authors: CHU de Québec Research Center, Quebec City, QC, Canada.
authors: Mélissa
authors: M
authors: Pelletier
authors: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, Canada.
authors: Laurent
authors: L
authors: Biertho
authors: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, Canada.
authors: Simon
authors: S
authors: Biron
authors: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, Canada.
authors: Simon
authors: S
authors: Marceau
authors: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, Canada.
authors: Frédéric-Simon
authors: FS
authors: Hould
authors: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, Canada.
authors: Stéfane
authors: S
authors: Lebel
authors: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, Canada.
authors: Fady
authors: F
authors: Moustarah
authors: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, Canada.
authors: Odette
authors: O
authors: Lescelleur
authors: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, Canada.
authors: Picard
authors: P
authors: Marceau
authors: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC, Canada; CHU de Québec Research Center, Quebec City, QC, Canada; Department of Nutrition, Laval University, Quebec City, Quebec, Canada.
authors: André
authors: A
authors: Tchernof
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000502:physiology*; D000328:Adult; D000368:Aged; D018929:Cell Culture Techniques; D054337:Cell Dedifferentiation; D048429:Cell Size; D016207:Cytokines / Q000235:genetics; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics*; D010450:Endopeptidases; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D018093:Gelatinases / Q000235:genetics*; D006801:Humans; D050152:Intra-Abdominal Fat / Q000166:cytology* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D012697:Serine Endopeptidases / Q000235:genetics*; D050151:Subcutaneous Fat / Q000166:cytology* / Q000378:metabolism; D015854:Up-Regulation; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D016207:Cytokines; D018819:Dipeptidyl Peptidase 4; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha; C042807:DPP4 protein, human