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

Abstract

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.

Endostatin Prevents Dietary-Induced Obesity by Inhibiting Adipogenesis and Angiogenesis

“…We find that endostatin inhibits adipogenesis by the mechanism of impairing Sam68-mediated alternative splicing of mTOR and reducing the activity of the mTORC1 pathway. In addition, we demonstrate that the well-known antiangiogenic activity of endostatin also contributes to its antiobesity effect, which is consistent with previous observations that several angiogenesis inhibitors, including angiostatin and TNP-470, prevent obesity in mice (13,14).…”

“…Similar to tumor tissue, WAT development in physiological and pathological contexts is accompanied by the formation of vascular networks (12,13), and several angiogenesis inhibitors have been reported to exert an antiobesity effect by inhibiting angiogenesis in adipose tissue (13,14). As a result of these studies, adipose tissue angiogenesis has a great potential as a therapeutic target for obesity and metabolic diseases (12).…”

The anti-angiogenic herbal composition Ob-X fromMorus alba,Melissa officinalis, andArtemisia capillarisregulates obesity in genetically obese ob/ob mice

“…In agreement with reductions in body weight gain, Ob-X significantly reduced mesenteric fat mass by 15% in obese ob/ob mice. Our previous study showed that treatment of high-fat diet-induced obese mice with Ob-X for 12 weeks reduced visceral fat mass by 38% (Kim et al, 2010). Lijnen et al (2002) also reported that administration of TNP-470 for 12 weeks induced decreases in visceral fat mass in highfat diet-fed mice.…”

The Angiogenesis Inhibitor ALS-L1023 from Lemon-Balm Leaves Attenuates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease through Regulating the Visceral Adipose-Tissue Function

“…It is suggested, therefore, that adipose tissue growth is angiogenesis-dependent and may be inhibited by angiogenesis inhibitors. Recently, we demonstrated that the anti-angiogenic dietary supplement Ob-X reduces adipose tissue mass and suppresses obesity by inhibiting angiogenesis [7]. …”