Activation of PPAR γ and α by punicic acid ameliorates glucose tolerance and suppresses obesity-related inflammation.

Objective: Peroxisome proliferator-activated receptor γ (PPAR γ) is the molecular target for thiazolidinediones (TZDs), a class of synthetic antidiabetic agents. However, the naturally occurring agonists of PPARs remain largely unknown. Punicic acid (PUA) is a conjugated linolenic acid isomer found in pomegrante. The objective of this study was to test the hypothesis that PUA activates PPAR γ and thereby ameliorates glucose homeostasis and obesity-related inflammation.Methods: The ability of PUA to modulate PPAR reporter activity was determined in 3T3-L1 pre-adipocytes. A cell-free assay was used to measure PUA's binding to the ligand-binding domain (LBD) of human PPAR γ. The preventive actions of PUA were investigated using genetically obese db/db mice and a model of diet-induced obesity in PPAR γ-expressing and tissue-specific PPAR γ null mice. Expression of PPAR α, γ, PPAR-responsive genes and TNF-α was measured in tissues controlling glucose homeostasis.Results: PUA caused a dose-dependent increase PP...