PMID- 18356826
OWN - NLM
STAT- MEDLINE
DCOM- 20080908
LR  - 20131121
IS  - 1930-7381 (Print)
IS  - 1930-7381 (Linking)
VI  - 16
IP  - 6
DP  - 2008 Jun
TI  - Effect of peroxisome proliferator-activated receptor-alpha ligands in the 
      interaction between adipocytes and macrophages in obese adipose tissue.
PG  - 1199-207
LID - 10.1038/oby.2008.62 [doi]
AB  - OBJECTIVE: This study was designed to examine the effect of peroxisome 
      proliferator-activated receptor-alpha (PPAR-alpha) ligands on the inflammatory 
      changes induced by the interaction between adipocytes and macrophages in obese 
      adipose tissue. METHODS AND PROCEDURES: PPAR-alpha ligands (Wy-14,643 and 
      fenofibrate) were added to 3T3-L1 adipocytes, RAW264 macrophages, or co-culture 
      of 3T3-L1 adipocytes and RAW264 macrophages in vitro, and monocyte 
      chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) 
      mRNA expression and secretion were examined. PPAR-alpha ligands were administered 
      to genetically obese ob/ob mice for 2 weeks. Moreover, the effect of PPAR-alpha 
      ligands was also evaluated in the adipose tissue explants and peritoneal 
      macrophages obtained from PPAR-alpha-deficient mice. RESULTS: In the co-culture 
      of 3T3-L1 adipocytes and RAW264 macrophages, PPAR-alpha ligands reduced MCP-1 and 
      TNF-alpha mRNA expression and secretion in vitro relative to vehicle-treated 
      group. The anti-inflammatory effect of Wy-14,643 was observed in adipocytes 
      treated with macrophage-conditioned media or mouse recombinant TNF-alpha and in 
      macrophages treated with adipocyte-conditioned media or palmitate. Systemic 
      administration of PPAR-alpha ligands inhibited the inflammatory changes in 
      adipose tissue from ob/ob mice. Wy-14,643 also exerted an anti-inflammatory 
      effect in the adipose tissue explants but not in peritoneal macrophages obtained 
      from PPAR-alpha-deficient mice. DISCUSSION: This study provides evidence for the 
      anti-inflammatory effect of PPAR-alpha ligands in the interaction between 
      adipocytes and macrophages in obese adipose tissue, thereby improving the 
      dysregulation of adipocytokine production and obesity-related metabolic syndrome.
FAU - Toyoda, Takuya
AU  - Toyoda T
AD  - Department of Molecular Medicine and Metabolism, Medical Research Institute, 
      Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
FAU - Kamei, Yasutomi
AU  - Kamei Y
FAU - Kato, Hirotsugu
AU  - Kato H
FAU - Sugita, Satoshi
AU  - Sugita S
FAU - Takeya, Motohiro
AU  - Takeya M
FAU - Suganami, Takayoshi
AU  - Suganami T
FAU - Ogawa, Yoshihiro
AU  - Ogawa Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080320
PL  - United States
TA  - Obesity (Silver Spring)
JT  - Obesity (Silver Spring, Md.)
JID - 101264860
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Ligands)
RN  - 0 (PPAR alpha)
RN  - 0 (Pyrimidines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 86C4MRT55A (pirinixic acid)
RN  - U202363UOS (Fenofibrate)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/*drug effects/metabolism/pathology
MH  - Animals
MH  - Anti-Inflammatory Agents/pharmacology
MH  - Cell Communication/*drug effects
MH  - Cell Line
MH  - Chemokine CCL2/metabolism
MH  - Coculture Techniques
MH  - Disease Models, Animal
MH  - Fenofibrate/*pharmacology
MH  - Ligands
MH  - Macrophages/*drug effects/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Obese
MH  - Obesity/*metabolism/pathology
MH  - PPAR alpha/genetics/*metabolism
MH  - Peritoneal Cavity/pathology
MH  - Pyrimidines/*pharmacology
MH  - RNA, Messenger/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2008/03/22 09:00
MHDA- 2008/09/09 09:00
CRDT- 2008/03/22 09:00
PHST- 2008/03/22 09:00 [pubmed]
PHST- 2008/09/09 09:00 [medline]
PHST- 2008/03/22 09:00 [entrez]
AID - oby200862 [pii]
AID - 10.1038/oby.2008.62 [doi]
PST - ppublish
SO  - Obesity (Silver Spring). 2008 Jun;16(6):1199-207. doi: 10.1038/oby.2008.62. Epub 
      2008 Mar 20.