Matrix Metalloproteinase Inhibition Impairs Adipose Tissue Development in Mice

Lijnen, H. Roger; Maquoi, Erik; Hansen, Ludo; Hoef, Berthe Van; Frederix, Liesbeth; Collen, D.

doi:10.1161/hq0302.104522

Cited by 117 publications

(110 citation statements)

References 42 publications

(46 reference statements)

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“…Ob-X treatment for 12 weeks in high fat diet-fed mice decreased adipose tissue mass by 43%, and this effect was higher than the results showing a 38% reduction after a 12-week administration of galadin, a broad spectrum inhibitor of MMP. 10 Our data are also supported by other results indicating that body weight gain and adipose tissue mass of obese animals were reduced significantly by several kinds of angiogenesis inhibitors. 6,32 In agreement with earlier studies, 10 Ob-X differentially regulated SC and VSC fat mass in obese mice.…”

Section: Inhibition Of Obesity By Angiogenesis Inhibitorsupporting

confidence: 90%

“…10 Our data are also supported by other results indicating that body weight gain and adipose tissue mass of obese animals were reduced significantly by several kinds of angiogenesis inhibitors. 6,32 In agreement with earlier studies, 10 Ob-X differentially regulated SC and VSC fat mass in obese mice. SC fat mass was decreased much greater than VSC fat mass.…”

Section: Inhibition Of Obesity By Angiogenesis Inhibitorsupporting

confidence: 90%

“…Two types of proteolytic systems, the plasminogen/plasmin (fibrolytic) and matrix metalloproteinase (MMP) systems, have been implicated in tissue remodeling, via degradation of ECM and basement membrane components, or activation of adipocyte growth factors. 9,10 The MMP system has important roles in the development of adipose tissue and microvessel maturation by modulating ECM. [10][11][12] In most cases, MMPs are expressed at very low levels, but expression is rapidly induced at times of active tissue remodeling associated with adipogenesis.…”

Section: Introductionmentioning

confidence: 99%

“…9,10 The MMP system has important roles in the development of adipose tissue and microvessel maturation by modulating ECM. [10][11][12] In most cases, MMPs are expressed at very low levels, but expression is rapidly induced at times of active tissue remodeling associated with adipogenesis. Several lines of evidence suggest that endogenous and exogenous MMPs regulate adipogenesis.…”

Section: Introductionmentioning

confidence: 99%

“…17 More clearly, MMP inhibition impairs development of adipose tissue in mice. 18 Thus, the adipocyte-derived MMPs may be new targets for the inhibition of adipose tissue growth.…”

Section: Introductionmentioning

confidence: 99%

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The anti-angiogenic herbal composition Ob-X inhibits adipose tissue growth in obese mice

My¹,

By²,

Hs³

et al. 2010

Int J Obes

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Objective: The growth and development of adipose tissue are thought to be associated with angiogenesis and extracellular matrix remodeling. As the composition of the herbal extract called Ob-X has been shown to have both anti-angiogenic and matrix metalloproteinase (MMP)-inhibiting activities, we hypothesized that growth of adipose tissue can be regulated by Ob-X. Materials and methods: The effects of Ob-X on angiogenesis and extracellular matrix remodeling were measured using in vitro and ex vivo assays. The effects of Ob-X on adipose tissue growth were investigated in nutritionally obese mice. Results: Ob-X inhibited angiogenesis in a dose-dependent manner in the human umbilical vein endothelial cell tube formation assay in vitro and the rat aortic ring assay ex vivo. Ob-X also suppressed MMP activity in vitro. Administration of Ob-X to high fat diet-induced obese mice produced significant reductions in body weight gain and adipose tissue mass compared with control. The mass of both visceral (VSC) and subcutaneous (SC) fat was reduced in Ob-X-treated mice. The size of adipocytes in VSC and SC adipose tissues was also significantly reduced in Ob-X-treated mice. Ob-X treatment decreased the blood vessel density and MMP activity in VSC adipose tissues of nutritionally obese mice. Ob-X reduced mRNA levels of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9), whereas it increased mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1 and TIMP-2) in SC and VSC adipose tissues of nutritionally obese mice. Conclusion: Ob-X, which has anti-angiogenic and MMP-inhibitory activities, reduces adipose tissue mass in nutritionally induced obese mice, providing evidence that adipose tissue growth and development may be prevented by inhibiting angiogenesis. In addition, these data suggest that regulation of adipose tissue growth by inhibiting angiogenesis may alter the expression of genes involved in angiogenesis and the MMP system.

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Section: Inhibition Of Obesity By Angiogenesis Inhibitorsupporting

confidence: 90%

Section: Inhibition Of Obesity By Angiogenesis Inhibitorsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…17 More clearly, MMP inhibition impairs development of adipose tissue in mice. 18 Thus, the adipocyte-derived MMPs may be new targets for the inhibition of adipose tissue growth.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The anti-angiogenic herbal composition Ob-X inhibits adipose tissue growth in obese mice

My¹,

By²,

Hs³

et al. 2010

Int J Obes

View full text Add to dashboard Cite

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Adipose Organ Development and Remodeling

Cinti

2018

Comprehensive Physiology

142

121

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During the last decades, research on adipose tissues has spread in parallel with the extension of obesity. Several observations converged on the idea that adipose tissues are organized in a large organ with endocrine and plastic properties. Two parenchymal components: white (WATs) and brown adipose tissues (BATs) are contained in subcutaneous and visceral compartments. Although both have endocrine properties, their function differs: WAT store lipids to allow intervals between meals, BAT burns lipids for thermogenesis. In spite of these opposite functions, they share the ability for reciprocal reversible transdifferentiation to tackle special physiologic needs. Thus, chronic need for thermogenesis induces browning and chronic positive energy balance induce whitening. Lineage tracing and data from explant studies strongly suggest other remodeling properties of this organ. During pregnancy and lactation breast WAT transdifferentiates into milk-secreting glands, composed by cells with abundant cytoplasmic lipids (pink adipocytes) and in the postlactation period pink adipocytes transdifferentiate back into WAT and BAT. The plastic properties of mature adipocytes are supported also by a liposecretion process in vitro where adult cell in culture transdifferentiate to differentiated fibroblast-like elements able to give rise to different phenotypes (rainbow adipocytes). In addition, the inflammasome system is activated in stressed adipocytes from obese adipose tissue. These adipocytes die and debris are reabsorbed by macrophages inducing a chronic low-grade inflammation, potentially contributing to insulin resistance and T2 diabetes. Thus, the plastic properties of this organ could open new therapeutic perspectives in the obesity-related metabolic disease and in breast pathologies. © 2018 American Physiological Society. Compr Physiol 8:1357-1431, 2018.

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Adipogenesis and insulin sensitivity in obesity are regulated by retinoid‐related orphan receptor gamma

et al. 2011

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Obesity is a well-known risk factor for the development of secondary complications such as type 2 diabetes. However, only a part of the obese population develops secondary metabolic disorders. Here, we identify the transcription factor retinoid-related orphan receptor gamma (RORγ) as a negative regulator of adipocyte differentiation through expression of its newly identified target gene matrix metalloproteinase 3. In vivo differentiation of adipocyte progenitor cells from Rorγ-deficient mice is enhanced and obese Rorγ−/− mice show decreased adipocyte sizes. These small adipocytes are highly insulin sensitive, leading to an improved control of circulating free fatty acids. Ultimately, Rorγ−/− mice are protected from hyperglycemia and insulin resistance in the state of obesity. In adipose stromal-vascular fraction from obese human subjects, Rorγ expression is correlated with adipocyte size and negatively correlated with adipogenesis and insulin sensitivity. Taken together, our findings identify RORγ as a factor, which controls adipogenesis as well as adipocyte size and modulates insulin sensitivity in obesity. RORγ might therefore serve as a novel pharmaceutical target to treat obesity-associated insulin resistance.

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Matrix Metalloproteinase Inhibition Impairs Adipose Tissue Development in Mice

Cited by 117 publications

References 42 publications

The anti-angiogenic herbal composition Ob-X inhibits adipose tissue growth in obese mice

The anti-angiogenic herbal composition Ob-X inhibits adipose tissue growth in obese mice

Adipose Organ Development and Remodeling

Adipogenesis and insulin sensitivity in obesity are regulated by retinoid‐related orphan receptor gamma

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