| Abstract | 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. |
| Authors | Amir J Guri, Raquel Hontecillas, Gerardo Ferrer, Oriol Casagran, Umesh Wankhade, Alexis M Noble, Decio L Eizirik, Fernanda Ortis, Miriam Cnop, Dongmin Liu, Hongwei Si, Josep Bassaganya-Riera
(Affiliation: Laboratory of Nutritional Immunology and Molecular Nutrition, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.)
|
| Journal | The Journal of nutritional biochemistry
(J Nutr Biochem)
Vol. 19
Issue 4
Pg. 216-28
(Apr 2008)
ISSN: 0955-2863 United States |
| PMID | 17618105
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Blood Glucose
- Chemokine CCL2
- PPAR gamma
- Triglycerides
- Abscisic Acid
|
| Topics |
- Abscisic Acid
(pharmacology)
- Adipose Tissue, White
(cytology, immunology, metabolism)
- Animals
- Blood Glucose
(metabolism)
- Body Weight
- Chemokine CCL2
(genetics, metabolism)
- Inflammation
(immunology, metabolism)
- Insulin Resistance
- Liver
(metabolism)
- Macrophages
(cytology, immunology, metabolism)
- Mice
- Mice, Inbred Strains
- Obesity
(metabolism)
- PPAR gamma
(deficiency, metabolism)
- Phenotype
- Triglycerides
(blood)
|
