title: Gelatinase A (MMP-2) promotes murine adipogenesis.
abstract: BACKGROUND
  Expansion of adipose tissue is dependent on adipogenesis, angiogenesis and extracellular matrix remodeling. A functional role in these processes was suggested for the gelatinase subfamily of the matrix metalloproteinases. Here, we have evaluated a potential role of gelatinase A (MMP-2) in adipogenesis.
  
  
  METHODS
  Murine embryonic fibroblasts (MEF) were derived from wild-type or MMP-2 deficient mice. Genetic manipulation of Mmp2 (shRNA-knockdown or overexpression) was performed in 3T3-F442A preadipocytes. Cell cultures were subjected to an adipogenic medium. As an in vivo model for de novo adipogenesis, 3T3-F442A preadipocytes with or without knockdown were injected subcutaneously in Nude BALB/c mice kept on high fat diet.
  
  
  RESULTS
  Mmp2 deficient MEF, as compared to controls, showed significantly impaired differentiation into mature adipocytes, as demonstrated by 90% reduced intracellular lipid content and reduced expression of pro-adipogenic markers. Moreover, selective Mmp2 knockdown in 3T3-F442A preadipocytes resulted in significantly reduced differentiation. In contrast, overexpression of Mmp2 resulted in markedly enhanced differentiation. In de novo formed fat pads resulting from preadipocytes with Mmp2 knockdown expression of aP2, Ppar-γ and adiponectin was significantly lower, and collagen was more preserved. The fat pad weights as well as size and density of adipocytes or blood vessels were, however, not significantly different from controls.
  
  
  CONCLUSIONS
  Our data directly support a functional role of MMP-2 in adipogenesis in vitro, and suggest a potential role in in vivo adipogenesis.
  
  
  CONCLUSIONS
  Selective modulation of MMP-2 levels affects adipogenesis.
authors: KU Leuven-University of Leuven, Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, B-3000 Leuven, Belgium.
authors: Dries
authors: D
authors: Bauters
authors: KU Leuven-University of Leuven, Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, B-3000 Leuven, Belgium.
authors: Ilse
authors: I
authors: Scroyen
authors: KU Leuven-University of Leuven, Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, B-3000 Leuven, Belgium.
authors: Matthias
authors: M
authors: Van Hul
authors: KU Leuven-University of Leuven, Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, B-3000 Leuven, Belgium. Electronic address: roger.lijnen@med.kuleuven.be.
authors: H Roger
authors: HR
authors: Lijnen
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D050156:Adipogenesis / Q000235:genetics*; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008819:Mice, Nude; D008859:Microscopy, Polarization; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D052242:Adiponectin; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D047495:PPAR gamma; D020778:Matrix Metalloproteinase 2
keywords: Adipogenesis; Gelatinase; Matrix metalloproteinase; Obesity; Preadipocyte