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: 4.98). 04/2002; 87(3):530-5.
Source: PubMed


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.

9 Reads
  • Source
    • "Inactivation of MMP3 on a high-fat diet results in increased development of adipose tissue with a hyperplastic as well as a hypertrophic response [31]. Similar observations were made after inactivation of MMP9 and MMP11 [24, 32]. Contrasting observations have been made with pharmacological inhibition of MMPs in mice on a high-fat diet. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The central role of the adipose tissue in lipid metabolism places specific demands on the cell structure of adipocytes. The protein composition and dynamics of the extracellular matrix (ECM) is of crucial importance for the functioning of those cells. Adipogenesis is a bi-phasic process in which the ECM develops from a fibrillar to a laminar structure as cells move from the commitment phase to the growth phase characterized by storage of vast amounts of triglycerides. Mature adipocytes appear to spend a lot of energy on the maintenance of the ECM. ECM remodeling is mediated by a balanced complement of constructive and destructive enzymes together with their enhancers and inhibitors. ECM remodeling is an energy costing process regulated by insulin, by the energy metabolism, and by mechanical forces. In the obese, overgrowth of adipocytes may lead to instability of the ECM, possibly mediated by hypoxia.
    Cellular and Molecular Life Sciences CMLS 04/2010; 67(8):1277-92. DOI:10.1007/s00018-010-0263-4 · 5.81 Impact Factor
  • Source
    • "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
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Obesity is a global public health problem. Traditional herbal medicines may have some potential in managing obesity. The dried fruit rind of Garcinia cambogia, also known as Malabar tamarind, is a unique source of (-)-hydroxycitric acid (HCA), which exhibits a distinct sour taste and has been safely used for centuries in Southeastern Asia to make meals more filling. Recently it has been demonstrated that when taken orally, a novel, highly soluble calcium/potassium salt of HCA (HCA-SX) is safe and bioavailable in the human plasma. Although HCA-SX seems to be conditionally effective in weight management in experimental animals and in humans, its mechanism of action remains unclear. In this study, subcutaneous preadipocytes collected from obese women with body mass index>25 kg/m2 were differentiated to adipocytes for 2 weeks in culture. The effects of low-dose HCA-SX on lipid metabolism and on the adipocyte transcriptome were tested. HCA-SX augmented isoproterenol- and 3-isobutyryl-1-methylxanthine-induced lipolysis. Using oil red O, the production of lipid storage droplets by the cultured mature human adipocytes was visualized and enumerated. HCA-SX caused droplet dispersion facilitating lipase action on the lipids. HCA-SX markedly induced leptin expression in the adipocytes. In the microarray analyses, a total of 54,676 probe sets were screened. HCA-SX resulted in significant down-regulation of 348, and induction of 366 fat- and obesity-related genes. HCA-SX induced transactivation of hypoxia inducible factor (HIF), a novel approach in the management of obesity. Taken together, the net effects support the antilipolytic and antiadipogenic effects of HCA-SX. Further human studies are warranted.
    DNA and Cell Biology 10/2007; 26(9):627-39. DOI:10.1089/dna.2007.0617 · 2.06 Impact Factor
Show more