title: Reduction of Adipose Tissue Mass by the Angiogenesis Inhibitor ALS-L1023 from Melissa officinalis.
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.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.|AngioLab, Inc., Daejeon, Korea.
authors.forename: Byung Young
authors.initials: BY
authors.lastname: Park
authors.affiliation: Department of Biomedical Engineering, Mokwon University, Daejeon, Korea.
authors.forename: Hyunghee
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, Mokwon University, Daejeon, Korea.
authors.forename: Sangee
authors.initials: S
authors.lastname: Woo
authors.affiliation: Department of Biomedical Engineering, Mokwon University, Daejeon, Korea.
authors.forename: Miso
authors.initials: M
authors.lastname: Yoon
authors.affiliation: Department of Biomedical Engineering, Mokwon University, Daejeon, Korea.
authors.forename: Jeongjun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, Mokwon University, Daejeon, Korea.
authors.forename: Yeonhee
authors.initials: Y
authors.lastname: Hong
authors.affiliation: AngioLab, Inc., Daejeon, Korea.
authors.forename: Hee Suk
authors.initials: HS
authors.lastname: Lee
authors.affiliation: AngioLab, Inc., Daejeon, Korea.
authors.forename: Eun Kyu
authors.initials: EK
authors.lastname: Park
authors.affiliation: AngioLab, Inc., Daejeon, Korea.
authors.forename: Jong Cheon
authors.initials: JC
authors.lastname: Hahm
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Formula Sciences, College of Oriental Medicine, Dongeui University, Busan, Korea.
authors.forename: Soon Shik
authors.initials: SS
authors.lastname: Shin
authors.affiliation: AngioLab, Inc., Daejeon, Korea.
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, Mokwon University, Daejeon, Korea.
authors.forename: Michung
authors.initials: M
authors.lastname: Yoon
mesh_terms: D017667:Adipocytes / Q000187:drug effects; D000273:Adipose Tissue / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D059305:Diet, High-Fat; D061307:Human Umbilical Vein Endothelial Cells; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D031334:Melissa / Q000737:chemistry*; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
chemical_list: C000608553:ALS-L1023; D020533:Angiogenesis Inhibitors; D008055:Lipids; D061965:Matrix Metalloproteinase Inhibitors; D047493:PPAR alpha; D010936:Plant Extracts; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9