Deficiency of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) impairs nutritionally induced obesity in mice.
Tissue inhibitor of matrix metalloproteinase-1 deficient (TIMP-1(-/-)) mice and wild-type (TIMP-1(+/+)) controls were kept on a standard (SFD) or a high fat diet (HFD) for 15 weeks. At the time of sacrifice, TIMP-1(-/-) mice on HFD had a significantly lower body weight (29 +/- 1.5 versus 41 +/- 1.8 g, p <0.005), and significantly less subcutaneous (0.81 +/- 0.19 versus 1.78 +/- 0.21 g, p <0.05) and gonadal (0.87 +/- 0.17 versus 1.85 +/- 0.18 g, p <0.005) fat mass. These differences were much less pronounced for mice on SFD. On HFD but not on SFD, adipocyte diameters were significantly lower in the adipose tissue of TIMP-1(-/-) mice. Plasma leptin levels in TIMP-1(-/-) mice on HFD were significantly lower as compared to TIMP-1(+/-) mice, and strongly correlated with adipose tissue mass for both genotypes. Staining with an endothelial cell specific lectin revealed a significantly higher blood vessel density, larger stained area and vessel size in adipose tissue of TIMP-1(-/-) mice on HFD. This difference disappeared after normalization to the adipocyte number, suggesting that it does not represent a true enhancement of angiogenesis. Thus, in a murine model of nutritionally induced obesity, TIMP-1 promotes adipose tissue development.
Lijnen
H Roger
HR
Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium. roger.lijnen@med.kuleuven.ac.be
Demeulemeester
Diego
D
Van Hoef
Berthe
B
Collen
Désiré
D
Maquoi
Erik
E
D017667:Adipocytes / Q000648:ultrastructure; D000273:Adipose Tissue / Q000098:blood supply / Q000201:enzymology / Q000473:pathology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D048429:Cell Size; D002784:Cholesterol / Q000097:blood; D003433:Crosses, Genetic; D004041:Dietary Fats / Q000008:administration & dosage / Q000633:toxicity; D004730:Endothelium, Vascular / Q000473:pathology; D018093:Gelatinases / Q000032:analysis; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000209:etiology; D009765:Obesity / Q000209:etiology* / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D004041:Dietary Fats; D020738:Leptin; D019715:Tissue Inhibitor of Metalloproteinase-1; D014280:Triglycerides; D002784:Cholesterol; D018093:Gelatinases