Reduction of adipose tissue mass by the angiogenesis inhibitor ALS-L1023

Abstract

Abstract Objective: Angiogenesis has been demonstrated to modulate adipogenesis and obesity. This study was undertaken to determine whether the botanical drug ALS-L1023 (ALS), which exhibits antiangiogenic activity, can regulate adipose tissue growth in high-fat-diet-induced obese mice. Materials and Methods: The effects of ALS on angiogenesis and extracellular matrix remodeling were measured using in vitro assays. The effects of ALS on adipose tissue growth was investigated in nutritionally obese mice. Results: ALS inhibited angiogenesis in a concentration-dependent manner in the tube formation assay and the VEGF-induced proliferation assay using human umbilical vein endothelial cells. ALS also suppressed matrix metalloproteinase (MMP) activity in vitro. ALS administration to high-fat-diet-induced obese mice significantly reduced body weight gain, adipose tissue mass, and adipocyte size compared with the findings in the controls. ALS treatment decreased blood vessel density and MMP activity in adipose tissues. ALS reduced the mRNA levels of angiogenic factors (VEGFs and FGF-2) and MMPs (MMP-2 and MMP-9), whereas it increased the mRNA levels of angiogenic inhibitors (TSP-1 and TIMPs) in adipose tissues. Conclusion: These results suggest that in vivo and in vitro treatment with ALS, which has antiangiogenic and MMP inhibitory activities, reduces adipose tissue mass in nutritionally induced obese mice, providing evidence that adipose tissue growth can be regulated by angiogenesis inhibitors.