Activation of PPARγ and δ by dietary punicic acid ameliorates intestinal inflammation in mice

• Published in: British journal of nutrition Vol. 106; no. 6; pp. 878 - 886
• Main Authors: Bassaganya-Riera, Josep, DiGuardo, Margaret, Climent, Montse, Vives, Cristina, Carbo, Adria, Jouni, Zeina E., Einerhand, Alexandra W. C., O'Shea, Marianne, Hontecillas, Raquel
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 28.09.2011; CABI Pub
• Subjects: Animal Feed; Animals; anti-inflammatory activity; Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; colitis; dextran; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Gene Deletion; genes; immunomodulation; Inflammation; Inflammatory Bowel Diseases - drug therapy; Interleukin-10 - genetics; Intestinal Mucosa - microbiology; Intestines - metabolism; Linolenic Acids - pharmacology; macrophages; Mice; Mice, Inbred C57BL; Mice, Transgenic; mucosa; Nutritional Immunology; PPAR delta - metabolism; PPAR gamma - metabolism; protective effect; sodium sulfate; T-Lymphocytes - cytology; T-Lymphocytes, Regulatory - cytology; tumor necrosis factor-alpha; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Inflammatory bowel disease; PPAR; Punicic acid; Digestive system; Rodentia; Gut; Activation; Inflammation; Inflammatory disease; Crohn disease; Vertebrata; Mammalia; Mouse; Animal; Digestive diseases; Intestinal disease; Peroxisome proliferator activated receptor; Ulcerative colitis
• ISSN: 0007-1145; 1475-2662
• DOI: 10.1017/S0007114511001188

The goal of the present study was to elucidate the mechanisms of immunoregulation by which dietary punicic acid (PUA) prevents or ameliorates experimental inflammatory bowel disease (IBD). The expression of PPARγ and δ, their responsive genes and pro-inflammatory cytokines was assayed in the colonic mucosa. Immune cell-specific PPARγ null, PPARδ knockout and wild-type mice were treated with PUA and challenged with 2·5 % dextran sodium sulphate (DSS). The prophylactic efficacy of PUA was examined in an IL-10− / −  model of IBD. The effect of PUA on the regulatory T-cell (Treg) compartment was also examined in mice with experimental IBD. PUA ameliorated spontaneous pan-enteritis in IL-10− / −  mice and DSS colitis, up-regulated Foxp3 expression in Treg and suppressed TNF-α, but the loss of functional PPARγ or δ impaired these anti-inflammatory effects. At the cellular level, the macrophage-specific deletion of PPARγ caused a complete abrogation of the protective effect of PUA, whereas the deletion of PPARδ or intestinal epithelial cell-specific PPARγ decreased its anti-inflammatory efficacy. We provide in vivo molecular evidence demonstrating that PUA ameliorates experimental IBD by regulating macrophage and T-cell function through PPARγ- and δ-dependent mechanisms.