The loss of PPAR γ in immune cells abrogates the ability of abscisic acid to improve insulin sensitivity through a mechanism involving suppression of MCP-1 expression and macrophage infiltration into white adipose tissue

Guri, A.J., R. Hontecillas, G. Ferrer, O. Casagran, U. Wankhade, A.M. Noble and J. Bassaganya-Riera (2007) The loss of PPAR g in immune cells abrogates the ability of abscisic acid to improve insulin sensitivity through a mechanism involving suppression of MCP-1 expression and macrophage infiltration into white adipose tissue. FASEB Meetings, Washington, D.C.; (Abstract #934).

Abcisic acid (ABA) is a natural phytohormone and PPARgamma agonist that significantly improves insulin sensitivity in db/db mice. Though 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 remains 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. The F4/80hi ATMs were more abundant and expressed greater concentrations of chemokine receptor 2 (CCR2) and CCR5 when compared to F4/80lo ATMs. ABA significantly decreased CCR2+F4/80hi infiltration into WAT and suppressed monocyte chemoattractant protein-1 (MCP-1) expression in WAT and plasma. Furthermore, the deficiency of PPARgamma inimmune cells, including macrophages, impaired the ability of ABA to suppress infiltration of F4/80hi ATMs into WAT, repress WAT MCP-1 expression and 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 F4/80hi ATM infiltration through a PPAR gamma-dependent mechanism.