Influence of t-pA and u-PA on adipose tissue development in a murine model of diet-induced obesity.
To investigate the potential role of tissue-type plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-PA) in development of adipose tissue, we have used a nutritionally induced obesity model in t-PA (t-PA-/-) and u-PA (u-PA-/-) deficient mice. Five week old male wild-type (WT), t-PA-/- or u-PA-/- mice (n = 9 to 16) were fed a high fat diet (HFD, 42% fat). After 16 weeks of HFD, the body weight of t-PA-/- mice was significantly higher than that of WT mice (48 +/- 1.1 g vs. 39 +/- 2.2 g, p = 0.004). The total weight of the isolated subcutaneous (sc) fat deposit was higher in t-PA-/- than in WT mice (2.4 +/- 0.22 g vs. 1.2 +/- 0.29 g, p = 0.002). accompanied with higher adipocyte diameters (80 +/- 1.7 microm vs. 61 +/- 4.7 microm, p < 0.01). These differences were not observed in the intra-abdominal fat deposit. The number of stroma cells in both adipose tissue territories was increased in t-PA-/- as compared to WT mice (2.0 +/- 0.13 vs. 1.5 +/- 0.10, p = 0.2 and 3.0 +/- 0.17 vs 1.6 +/- 0.17, p = 0.0001, stroma cells/adipocytes in sc and intra-abdominal tissue, respectively), partly as a result of an increased number of endothelial cells (192 +/- 9 vs. 154 +/-18, p = 0.06 and 108 +/- 13 vs. 69 +/- 8, p = 0.04 CD31 stained/adipocyte area). In contrast the weight gain and adipose tissue development in u-PA-/- mice was not different from that in WT mice. These data suggest that t-PA but not u-PA plays a role in adipose tissue development.
Morange
P E
PE
Haematology Laboratory, CHU Timone, Marseilles, France.
Bastelica
D
D
Bonzi
M F
MF
Van Hoef
B
B
Collen
D
D
Juhan-Vague
I
I
Lijnen
H R
HR
D017667:Adipocytes / Q000473:pathology; D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D001835:Body Weight; D002452:Cell Count; D004041:Dietary Fats / Q000633:toxicity; D005342:Fibrinolysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D017154:Stromal Cells / Q000473:pathology; D010959:Tissue Plasminogen Activator / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014568:Urokinase-Type Plasminogen Activator / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D004041:Dietary Fats; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator