| Title | Activation of PPAR {gamma} and {alpha} by Punicic Acid Ameliorates Glucose Tolerance and Suppresses Obesity-Related Inflammation. | | Author(s) | Hontecillas R, O'Shea M, Einerhand A, Diguardo M, Bassaganya-Riera J | | Institution | Laboratory of Nutritional Immunology & Molecular Nutrition, Virginia Bioinformatics Institute, Virginia Tech, 1 Washington Street, Blacksburg, VA 24061. jbassaga@vt.edu. | | Source | J Am Coll Nutr 2009 Apr; 28(2):184-95. | | 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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 19828904 |
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