Abstract

Abstract Objective: The growth and development of adipose tissue are thought to be associated with angiogenesis and extracellular matrix remodeling. Since 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 with nutritionally obese mice. Results: Ob-X inhibited angiogenesis in a dose-dependent manner in the human umbilical vein endothelial cell (HUVEC) 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 to controls. The mass of both subcutaneous (SC) and visceral (VSC) fat was reduced in Ob-X-treated mice. The size of adipocytes in SC and VSC 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 angiogenesis inhibitors (TSP-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.

Highlights

  • Obesity is the result of an energy imbalance caused by an increased ratio of caloric intake to energy expenditure

  • When Ob-X was added to the culture, the capillary-like tube formation of human umbilical vein endothelial cell (HUVEC) was inhibited in a dose-dependent manner compared with control

  • Effects of Ob-X on vascularization in VSC adipose tissue of obese mice To determine whether the decrease of adipose tissue mass by Ob-X is due to the inhibition of angiogenesis, we studied the effects of Ob-X on blood vessel density in VSC adipose tissue

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Summary

Introduction

Obesity is the result of an energy imbalance caused by an increased ratio of caloric intake to energy expenditure. Adipose tissue is highly vascularized, and each adipocyte is nourished by an extensive capillary network.[2,4,5] It is suggested, that adipose tissue growth is angiogenesis-dependent and may be inhibited by angiogenesis inhibitors. This is supported by reports that treatment with angiogenesis inhibitors resulted in weight reduction and adipose tissue loss, showing that adipose tissue mass is sensitive to angiogenesis inhibitors and can be regulated by its vasculature.[6,7,8]

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