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J Am Coll Nutr. 2009 Apr;28(2):184-95.

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

Author information

1
Laboratory of Nutritional Immunology & Molecular Nutrition, Virginia Bioinformatics Institute, Virginia Tech, 1 Washington Street, Blacksburg, VA 24061, USA.

Abstract

OBJECTIVE:

Peroxisome proliferator-activated receptor gamma (PPAR gamma) 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 gamma 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 gamma. The preventive actions of PUA were investigated using genetically obese db/db mice and a model of diet-induced obesity in PPAR gamma-expressing and tissue-specific PPAR gamma null mice. Expression of PPAR alpha, gamma, PPAR-responsive genes and TNF-alpha was measured in tissues controlling glucose homeostasis.

RESULTS:

PUA caused a dose-dependent increase PPAR alpha and gamma reporter activity in 3T3-L1 cells and bound although weakly to the LBD of human PPAR gamma. Dietary PUA decreased fasting plasma glucose concentrations, improved the glucose-normalizing ability, suppressed NF-kappaB activation, TNF-alpha expression and upregulated PPAR alpha- and gamma-responsive genes in skeletal muscle and adipose tissue. Loss of PPAR gamma impaired the ability of dietary PUA to improve glucose homeostasis and suppress inflammation.

CONCLUSIONS:

Our studies demonstrate that PUA binds and robustly activates PPAR gamma, increases PPAR gamma-responsive gene expression and the loss of PPAR gamma in immune cells impairs its ability to ameliorate diabetes and inflammation.

PMID:
19828904
[Indexed for MEDLINE]

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