PMID- 26901838
OWN - NLM
STAT- MEDLINE
DCOM- 20160726
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 2
DP  - 2016
TI  - The Dietary Isoflavone Daidzein Reduces Expression of Pro-Inflammatory Genes 
      through PPARalpha/gamma and JNK Pathways in Adipocyte and Macrophage Co-Cultures.
PG  - e0149676
LID - 10.1371/journal.pone.0149676 [doi]
LID - e0149676
AB  - 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 
      PPARalpha antagonist), and GW9662 (a PPARgamma 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-gamma 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-alpha inhibitor. 
      Additionally, we examined the activation of nuclear factor-kappa B (NF-kappaB) 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-alpha and -gamma 
      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.
FAU - Sakamoto, Yuri
AU  - Sakamoto Y
AD  - Department of Nutrition and Food Science, Graduate School of Humanities and 
      Sciences, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo, Japan.
FAU - Kanatsu, Junko
AU  - Kanatsu J
AD  - Department of Nutrition and Food Science, Graduate School of Humanities and 
      Sciences, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo, Japan.
FAU - Toh, Mariko
AU  - Toh M
AD  - Department of Nutrition and Food Science, Graduate School of Humanities and 
      Sciences, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo, Japan.
FAU - Naka, Ayano
AU  - Naka A
AD  - Laboratory of Applied Nutrition, Faculty of Human Life and Environmental 
      Sciences, Ochanomizu University, Tokyo, Japan.
FAU - Kondo, Kazuo
AU  - Kondo K
AD  - Endowed Research Department "Food for Health", Ochanomizu University, Tokyo, 
      Japan.
FAU - Iida, Kaoruko
AU  - Iida K
AD  - Department of Nutrition and Food Science, Graduate School of Humanities and 
      Sciences, Ochanomizu University, Otsuka, Bunkyo-ku, Tokyo, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160222
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Inflammation Mediators)
RN  - 0 (Isoflavones)
RN  - 0 (PPAR alpha)
RN  - 0 (PPAR gamma)
RN  - 6287WC5J2L (daidzein)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/*drug effects/*metabolism
MH  - Animals
MH  - Cell Line, Tumor
MH  - Coculture Techniques
MH  - Gene Expression Regulation/*drug effects
MH  - Humans
MH  - Inflammation Mediators/metabolism
MH  - Isoflavones/*pharmacology
MH  - JNK Mitogen-Activated Protein Kinases/*metabolism
MH  - Macrophages/*drug effects/*metabolism
MH  - Mice
MH  - PPAR alpha/*metabolism
MH  - PPAR gamma/*metabolism
MH  - Phosphorylation
MH  - Signal Transduction/*drug effects
PMC - PMC4763373
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2016/02/24 06:00
MHDA- 2016/07/28 06:00
PMCR- 2016/02/22
CRDT- 2016/02/23 06:00
PHST- 2015/10/06 00:00 [received]
PHST- 2016/02/02 00:00 [accepted]
PHST- 2016/02/23 06:00 [entrez]
PHST- 2016/02/24 06:00 [pubmed]
PHST- 2016/07/28 06:00 [medline]
PHST- 2016/02/22 00:00 [pmc-release]
AID - PONE-D-15-44009 [pii]
AID - 10.1371/journal.pone.0149676 [doi]
PST - epublish
SO  - PLoS One. 2016 Feb 22;11(2):e0149676. doi: 10.1371/journal.pone.0149676. 
      eCollection 2016.