RRC ID 64908
Author Sakamoto Y, Kanatsu J, Toh M, Naka A, Kondo K, Iida K.
Title The Dietary Isoflavone Daidzein Reduces Expression of Pro-Inflammatory Genes through PPARα/γ and JNK Pathways in Adipocyte and Macrophage Co-Cultures.
Journal PLoS One
Abstract Obesity-induced inflammation caused by adipocyte-macrophage interactions plays a critical role in developing insulin resistance, and peroxisome proliferator-activated receptors (PPARs) regulate inflammatory gene expression in these cells. Recently, the soy isoflavone daidzein was reported to act as a PPAR activator. We examined whether daidzein affected adipocyte-macrophage crosstalk via the regulation of PPARs. Co-cultures of 3T3-L1 adipocytes and RAW264 macrophages, or palmitate-stimulated RAW264 macrophages were treated with daidzein in the presence or absence of specific inhibitors for PPARs: GW6471 (a PPARα antagonist), and GW9662 (a PPARγ antagonist). Inflammatory gene expression was then determined. Daidzein significantly decreased chemokine (C-C motif) ligand 2 (Ccl2, known in humans as monocyte chemo-attractant protein 1 (MCP1)) and interleukin 6 (Il6) mRNA levels induced by co-culture. In 3T3-L1 adipocytes, daidzein inversed the attenuation of adiponectin gene expression by co-culture, and these effects were inhibited by the PPAR-γ specific inhibitor. Daidzein also decreased Ccl2 and Il6 mRNA levels in RAW264 macrophages stimulated with palmitate or conditioned medium (CM) from hypertrophied 3T3-L1 adipocytes. This inhibitory effect on Il6 expression was abrogated by a PPAR-α inhibitor. Additionally, we examined the activation of nuclear factor-kappa B (NF-κB) and c-Jun N-terminal kinase (JNK) pathways and found that daidzein significantly inhibited palmitate-induced phosphorylation of JNK. Our data suggest that daidzein regulates pro-inflammatory gene expression by activating PPAR-α and -γ and inhibiting the JNK pathway in adipocyte and macrophage co-cultures. These effects might be favorable in improving adipose inflammation, thus, treatment of daidzein may be a therapeutic strategy for chronic inflammation in obese adipose tissue.
Volume 11(2)
Pages e0149676
Published 2016-1-1
DOI 10.1371/journal.pone.0149676
PII PONE-D-15-44009
PMID 26901838
PMC PMC4763373
MeSH 3T3-L1 Cells Adipocytes / drug effects* Adipocytes / metabolism* Animals Cell Line, Tumor Coculture Techniques Gene Expression Regulation / drug effects* Humans Inflammation Mediators / metabolism Isoflavones / pharmacology* JNK Mitogen-Activated Protein Kinases / metabolism* Macrophages / drug effects* Macrophages / metabolism* Mice PPAR alpha / metabolism* PPAR gamma / metabolism* Phosphorylation Signal Transduction / drug effects*
IF 2.74
Human and Animal Cells 293T(RCB2202)