Adipocyte hypertrophy in stromelysin-3 deficient mice with nutritionally induced obesity.

Center for Molecular and Vascular Biology, University of Leuven, Belgium.
Thrombosis and Haemostasis (Impact Factor: 5.76). 04/2002; 87(3):530-5.
Source: PubMed

ABSTRACT Several matrix metalloproteinases (MMPs), including the stromelysins MMP-3 and MMP-11, are expressed in adipose tissue. To investigate a potential role of MMP-11 (stromelysin-3) in adipose tissue development, five-week-old male wild-type mice (MMP-11+/+) or mice with deficiency of MMP-11 (MMP-11-/-) were fed a high fat diet (HFD, 42% fat) for 15 weeks. Haematologic parameters, including white and red blood cells, platelets, haemoglobin and haematocrit, and metabolic parameters including glucose, triglycerides and total cholesterol were not different for both genotypes. At the time of sacrifice, the body weight of the MMP-11-/- mice was higher than that of the MMP-11+/+ mice (36+/-1.4 g versus 29+/-0.9 g, p = 0.0002). The weight of the isolated subcutaneous (SC) and gonadal (GON) fat deposits was also higher in MMP-11-/- mice (620+/-150 mg versus 280+/-28 mg for SC fat, and 970+/-180 mg versus 430+/-62 mg, p < 0.05, for GON fat). Adipocytes in MMP-11-/- adipose tissue were hypertrophic as compared to MMP-11+/+ adipocytes (volume of 57+/-12 x 10(3) microm3 versus 31+/-2.4 x 10(3) microm3 for SC fat, and 100+/-18 x 10(3) microm3 versus 57+/-7.6 x 10(3) microm3 for GON fat; both p < 0.06). In nutritionally induced obesity models in mice a potential role of the fibrinolytic system was suggested in adipocyte hypertrophy. The hypertrophy observed in this model is, however, not related to changes in fibrinolytic parameters, as suggested by our finding that levels of t-PA, u-PA and PAI-1 antigen as well as t-PA and u-PA activity were not different in SC or GON adipose tissue extracts of both genotypes. As the main biological function of MMP-11 remains unknown, it is not clear whether the adipocyte hypertrophy in MMP-11-/- adipose tissue is directly related to the deficiency or to other pathways affected by MMP-11.

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    • "MMP3 (or stromelysin 1) has been found to activate MMP1 and impair adipose tissue development [30] [31]. Low levels of stromelysins (such as MMP3 and MMP10) have been linked to obesity [30] [32]. MMP10 degrades extracellular matrix thereby negatively regulates angiogenesis and vascular remodeling [33]. "
    Genomics, Proteomics, and Metabolomics in Nutraceuticals and Functional Foods, 03/2010: pages 45 - 59; , ISBN: 9780813821474
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    • "Stromelysin, a member of the metalloproteinase gene family, plays a crucial role in the turnover of connective tissues. MMP-3 and MMP-10 are also known as stromelysin 1 and 2. Lower stromelysin levels have been linked to obesity (Lijnen et al., 2002; Maquoi et al., 2003). When MMP-3 À=À and wild-type controls were kept on a high-fat diet for 15 weeks, FIG. 8. HCA-SX induced HIF-1 transactivation and increased the expression of HIF-driven gene VEGF. "
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