title: Stromal cells are the main plasminogen activator inhibitor-1-producing cells in human fat: evidence of differences between visceral and subcutaneous deposits.
abstract: Elevated plasma plasminogen activator inhibitor (PAI)-1 observed during insulin resistance has been connected with an excessive PAI-1 adipose tissue secretion mainly by visceral fat. Our aim was to compare the localization of PAI-1 in human visceral and subcutaneous fats. PAI-1 secretion was also investigated in vitro during human adipocyte differentiation. PAI-1 antigen and mRNA were localized in the stromal area of the tissue and were also present in a few CD14-positive monocytes, in direct contact with adipocytes. In addition, in subcutaneous tissue, PAI-1 mRNA contents, determined by using real-time polymerase chain reaction, were higher in the stromal fraction than in the adipocyte fraction. PAI-1 mRNA-positive cells were 5-fold more frequent in the visceral area than in the subcutaneous stromal area (P=0.004). Such a difference was also observed for PAI-1 mRNA content between both whole adipose tissues. In contrast to leptin, during adipocyte differentiation, PAI-1 secretion did not follow adipocyte maturation. In situ hybridization in culture did not reveal PAI-1 mRNA in lipid-filled cells. Our results demonstrate that PAI-1 production is mainly due to stromal cells, which were more numerous in the visceral than in the subcutaneous depot. These results could explain the strong relationship observed between circulating PAI-1 levels and the accumulation of visceral fat.
authors.affiliation: Laboratoire d'Hématologie, Faculté de Médecine Timone, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Bastelica
authors.forename: Pierre
authors.initials: P
authors.lastname: Morange
authors.forename: Bruno
authors.initials: B
authors.lastname: Berthet
authors.forename: Hélène
authors.initials: H
authors.lastname: Borghi
authors.forename: Odile
authors.initials: O
authors.lastname: Lacroix
authors.forename: Michel
authors.initials: M
authors.lastname: Grino
authors.forename: Irène
authors.initials: I
authors.lastname: Juhan-Vague
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Alessi
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000273:Adipose Tissue / Q000737:chemistry* / Q000166:cytology; D000328:Adult; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis; D017154:Stromal Cells / Q000378:metabolism
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger