Abietic acid activates peroxisome proliferator-activated receptor-gamma (PPARgamma) in RAW264.7 macrophages and 3T3-L1 adipocytes to regulate gene expression involved in inflammation and lipid metabolism.
Abietic acid is one of the terpenoids, which are multifunctional natural compounds. It has been reported that abietic acid suppresses effects on inflammation. However, the mechanism underlying the anti-inflammatory effects remains unclear. The present work indicates that abietic acid suppresses the protein expression of tumor necrosis factor-alpha and cyclooxygenase 2, which are involved in inflammation, in lipopolysaccharide-stimulated macrophages. Moreover, this effect resembles that of thiazolidinedione, a synthetic peroxisome proliferator-activated receptor-gamma (PPARgamma) ligand. Indeed, abietic acid activates PPARgamma in luciferase reporter assays. The activity of abietic acid induces PPARgamma target gene expression in RAW264.7 macrophages and 3T3-L1 adipocytes. These data indicate that abietic acid is a PPARgamma ligand and that its anti-inflammatory effect is partly due to the activation of PPARgamma in stimulated macrophages. The present work suggests a novel possibility that abietic acid, a naturally occurring compound, can be used not only for anti-inflammation but also for regulating lipid metabolism and atherosclerosis.
Takahashi
Nobuyuki
N
Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
Kawada
Teruo
T
Goto
Tsuyoshi
T
Kim
Chu-Sook
CS
Taimatsu
Aki
A
Egawa
Kahori
K
Yamamoto
Takayuki
T
Jisaka
Mitsuo
M
Nishimura
Koji
K
Yokota
Kazushige
K
Yu
Rina
R
Fushiki
Tohru
T
D016475:3T3 Cells / Q000187:drug effects; D045784:Abietanes; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D018955:CD36 Antigens / Q000187:drug effects / Q000235:genetics; D050882:CREB-Binding Protein; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D004224:Diterpenes / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007249:Inflammation / Q000235:genetics; D007527:Isoenzymes / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D050356:Lipid Metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008156:Luciferases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009687:Nuclear Proteins / Q000187:drug effects / Q000235:genetics; D010616:Phenanthrenes / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D015534:Trans-Activators / Q000187:drug effects / Q000235:genetics; D014157:Transcription Factors / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D045784:Abietanes; D018955:CD36 Antigens; D004224:Diterpenes; D007527:Isoenzymes; D008024:Ligands; D008070:Lipopolysaccharides; D009687:Nuclear Proteins; D010616:Phenanthrenes; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D015534:Trans-Activators; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C089946:2,4-thiazolidinedione; D008156:Luciferases; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; C023710:abietic acid