Effect of tissue inhibitor of matrix metalloproteinases-1 on in vitro and in vivo adipocyte differentiation.
Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a role in development of obesity by contributing to adipogenesis, angiogenesis and extracellular matrix degradation. We have evaluated a potential functional role of TIMP-1, which inhibits most MMPs, in early stages of in vitro and in vivo adipogenesis. Overexpression of human TIMP-1 (hTIMP-1) in 3T3-F442A preadipocytes resulted in a somewhat slower differentiation into mature adipocytes, without affecting the total extent of differentiation. Local overexpression by injection of 3T3-F442A preadipocytes expressing hTIMP-1 in the back of NUDE mice kept on high fat diet (HFD) for 4 weeks, had no effect on de novo formed fat pad mass. The fat pads formed from the hTIMP-1 expressing cells did show a significantly larger blood vessel size as compared to control cells (57 + or - 4.8 microm(2) vs 38 + or - 1.4 microm(2), p=0.0017). No effect was observed on blood vessel density or on adipocyte size or density. Thus, local hTIMP-1 overexpression did not significantly affect early stages of adipogenesis as evaluated from the extent of in vitro adipocyte differentiation or of in vivo de novo adipose tissue formation.
Scroyen
Ilse
I
Center for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium.
Cosemans
Leentje
L
Lijnen
H Roger
HR
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection
D061965:Matrix Metalloproteinase Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9