PMID- 17618105
OWN - NLM
STAT- MEDLINE
DCOM- 20080507
LR  - 20131121
IS  - 0955-2863 (Print)
IS  - 0955-2863 (Linking)
VI  - 19
IP  - 4
DP  - 2008 Apr
TI  - Loss of PPAR gamma in immune cells impairs the ability of abscisic acid to 
      improve insulin sensitivity by suppressing monocyte chemoattractant protein-1 
      expression and macrophage infiltration into white adipose tissue.
PG  - 216-28
AB  - Abscisic acid (ABA) is a natural phytohormone and peroxisome 
      proliferator-activated receptor gamma (PPARgamma) agonist that significantly 
      improves insulin sensitivity in db/db mice. Although it has become clear that 
      obesity is associated with macrophage infiltration into white adipose tissue 
      (WAT), the phenotype of adipose tissue macrophages (ATMs) and the mechanisms by 
      which insulin-sensitizing compounds modulate their infiltration remain unknown. 
      We used a loss-of-function approach to investigate whether ABA ameliorates 
      insulin resistance through a mechanism dependent on immune cell PPARgamma. We 
      characterized two phenotypically distinct ATM subsets in db/db mice based on 
      their surface expression of F4/80. F4/80(hi) ATMs were more abundant and 
      expressed greater concentrations of chemokine receptor (CCR) 2 and CCR5 when 
      compared to F4/80(lo) ATMs. ABA significantly decreased CCR2(+) F4/80(hi) 
      infiltration into WAT and suppressed monocyte chemoattractant protein-1 (MCP-1) 
      expression in WAT and plasma. Furthermore, the deficiency of PPARgamma in immune 
      cells, including macrophages, impaired the ability of ABA to suppress the 
      infiltration of F4/80(hi) ATMs into WAT, to repress WAT MCP-1 expression and to 
      improve glucose tolerance. We provide molecular evidence in vivo demonstrating 
      that ABA improves insulin sensitivity and obesity-related inflammation by 
      inhibiting MCP-1 expression and F4/80(hi) ATM infiltration through a 
      PPARgamma-dependent mechanism.
FAU - Guri, Amir J
AU  - Guri AJ
AD  - Laboratory of Nutritional Immunology and Molecular Nutrition, Virginia 
      Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
FAU - Hontecillas, Raquel
AU  - Hontecillas R
FAU - Ferrer, Gerardo
AU  - Ferrer G
FAU - Casagran, Oriol
AU  - Casagran O
FAU - Wankhade, Umesh
AU  - Wankhade U
FAU - Noble, Alexis M
AU  - Noble AM
FAU - Eizirik, Decio L
AU  - Eizirik DL
FAU - Ortis, Fernanda
AU  - Ortis F
FAU - Cnop, Miriam
AU  - Cnop M
FAU - Liu, Dongmin
AU  - Liu D
FAU - Si, Hongwei
AU  - Si H
FAU - Bassaganya-Riera, Josep
AU  - Bassaganya-Riera J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070706
PL  - United States
TA  - J Nutr Biochem
JT  - The Journal of nutritional biochemistry
JID - 9010081
RN  - 0 (Blood Glucose)
RN  - 0 (Chemokine CCL2)
RN  - 0 (PPAR gamma)
RN  - 0 (Triglycerides)
RN  - 72S9A8J5GW (Abscisic Acid)
SB  - IM
MH  - Abscisic Acid/*pharmacology
MH  - Adipose Tissue, White/cytology/*immunology/metabolism
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Body Weight
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Inflammation/immunology/*metabolism
MH  - *Insulin Resistance
MH  - Liver/metabolism
MH  - Macrophages/cytology/*immunology/metabolism
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Obesity/metabolism
MH  - PPAR gamma/deficiency/*metabolism
MH  - Phenotype
MH  - Triglycerides/blood
EDAT- 2007/07/10 09:00
MHDA- 2008/05/08 09:00
CRDT- 2007/07/10 09:00
PHST- 2006/11/17 00:00 [received]
PHST- 2007/02/06 00:00 [revised]
PHST- 2007/02/14 00:00 [accepted]
PHST- 2007/07/10 09:00 [pubmed]
PHST- 2008/05/08 09:00 [medline]
PHST- 2007/07/10 09:00 [entrez]
AID - S0955-2863(07)00080-0 [pii]
AID - 10.1016/j.jnutbio.2007.02.010 [doi]
PST - ppublish
SO  - J Nutr Biochem. 2008 Apr;19(4):216-28. doi: 10.1016/j.jnutbio.2007.02.010. Epub 
      2007 Jul 6.