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

Nobuyuki Takahashi; Teruo Kawada; Tsuyoshi Goto; Chu-Sook Kim; Aki Taimatsu; Kahori Egawa; Takayuki Yamamoto; Mitsuo Jisaka; Koji Nishimura; Kazushige Yokota; Rina Yu; Tohru Fushiki

doi:10.1016/s0014-5793(03)00859-7

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

FEBS Lett. 2003 Aug 28;550(1-3):190-4. doi: 10.1016/s0014-5793(03)00859-7.

Authors

Nobuyuki Takahashi¹, Teruo Kawada, Tsuyoshi Goto, Chu-Sook Kim, Aki Taimatsu, Kahori Egawa, Takayuki Yamamoto, Mitsuo Jisaka, Koji Nishimura, Kazushige Yokota, Rina Yu, Tohru Fushiki

Affiliation

¹ Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.

PMID: 12935909
DOI: 10.1016/s0014-5793(03)00859-7

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3T3 Cells / drug effects
Abietanes*
Adipocytes / drug effects*
Adipocytes / metabolism
Animals
CD36 Antigens / drug effects
CD36 Antigens / genetics
CREB-Binding Protein
Cells, Cultured
Cyclooxygenase 2
Diterpenes / pharmacology*
Gene Expression Regulation / drug effects*
Inflammation / genetics
Isoenzymes / drug effects
Isoenzymes / genetics
Isoenzymes / metabolism
Ligands
Lipid Metabolism
Lipopolysaccharides / pharmacology
Luciferases / drug effects
Luciferases / genetics
Luciferases / metabolism
Macrophages, Peritoneal / drug effects*
Macrophages, Peritoneal / metabolism
Male
Mice
Mice, Inbred BALB C
Nuclear Proteins / drug effects
Nuclear Proteins / genetics
Phenanthrenes / pharmacology*
Prostaglandin-Endoperoxide Synthases / drug effects
Prostaglandin-Endoperoxide Synthases / genetics
Prostaglandin-Endoperoxide Synthases / metabolism
Receptors, Cytoplasmic and Nuclear / drug effects*
Receptors, Cytoplasmic and Nuclear / genetics
Receptors, Cytoplasmic and Nuclear / metabolism
Thiazoles / pharmacology
Thiazolidinediones*
Trans-Activators / drug effects
Trans-Activators / genetics
Transcription Factors / drug effects*
Transcription Factors / genetics
Transcription Factors / metabolism
Tumor Necrosis Factor-alpha / genetics
Tumor Necrosis Factor-alpha / metabolism

Substances

Abietanes
CD36 Antigens
Diterpenes
Isoenzymes
Ligands
Lipopolysaccharides
Nuclear Proteins
Phenanthrenes
Receptors, Cytoplasmic and Nuclear
Thiazoles
Thiazolidinediones
Trans-Activators
Transcription Factors
Tumor Necrosis Factor-alpha
2,4-thiazolidinedione
Luciferases
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases
CREB-Binding Protein
Crebbp protein, mouse
abietic acid