Abstract
It has been suggested that angiogenesis modulates adipogenesis and obesity. This study was undertaken to determine whether ALS-L1023 (ALS) prepared by a two-step organic solvent fractionation from Melissa leaves, which exhibits antiangiogenic activity, can regulate adipose tissue growth. The effects of ALS on angiogenesis and extracellular matrix remodeling were measured using in vitro assays. The effects of ALS on adipose tissue growth were investigated in high fat diet-induced obese mice. ALS inhibited VEGF- and bFGF-induced endothelial cell proliferation and suppressed matrix metalloproteinase (MMP) activity in vitro. Compared to obese control mice, administration of ALS to obese mice reduced body weight gain, adipose tissue mass and adipocyte size without affecting appetite. ALS treatment decreased blood vessel density and MMP activity in adipose tissues. ALS reduced the mRNA levels of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9), whereas ALS increased the mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2) in adipose tissues. The protein levels of VEGF, MMP-2 and MMP-9 were also decreased by ALS in adipose tissue. Metabolic changes in plasma lipids, liver triglycerides, and hepatic expression of fatty acid oxidation genes occurred during ALS-induced weight loss. These results suggest that ALS, which has antiangiogenic and MMP inhibitory activities, reduces adipose tissue mass in nutritionally obese mice, demonstrating that adipose tissue growth can be regulated by angiogenesis inhibitors.
Highlights
The development of obesity is associated with extensive modifications of adipose tissue involving adipogenesis, angiogenesis and extracellular matrix (ECM) remodeling [1].Similar to tumor growth, angiogenesis occurs in growing adipose tissue of adults
The growth and expansion of adipose tissue requires the formation of new blood vessels to provide oxygen and nutrients to adipocytes
Demonstrated that the antiangiogenic dietary supplement, Ob-X which is composed of a standardized mixture of Melissa officinalis L., Morus alba L. and Artemisia capillaris Thunb. aqueous extract reduces adipose tissue mass and suppresses obesity by inhibiting angiogenesis in nutritionally and genetically obese mice [14, 19]
Summary
The development of obesity is associated with extensive modifications of adipose tissue involving adipogenesis, angiogenesis and extracellular matrix (ECM) remodeling [1]. Angiogenesis (the formation of new blood vessels from pre-existing vessels) occurs in growing adipose tissue of adults. Most tissues normally do not grow throughout adulthood and the supporting vasculature is quiescent, whereas adipose tissue can PLOS ONE | DOI:10.1371/journal.pone.0141612. Angiogenesis Inhibition and Adipose Tissue Reduction study design, data collection and analysis, decision to publish, or preparation of the manuscript Most tissues normally do not grow throughout adulthood and the supporting vasculature is quiescent, whereas adipose tissue can PLOS ONE | DOI:10.1371/journal.pone.0141612 November 23, 2015
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