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.

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
• Journal: The Journal of nutritional biochemistry (J Nutr Biochem) Vol. 19 Issue 4 Pg. 216-28 (Apr 2008) ISSN: 0955-2863 [Print] 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)