Activation of PPAR γ and δ by CLA mediates protection against colitis

J. Bassaganya-Riera, K. Reynolds, S. Martino-Catt, Y. Cui, L. Hennighausen, F.J. Gonzalez, and R. Hontecillas (2004) Activation of PPAR g and d by CLA mediates protection against colitis. FASEB Meetings, Washington, D.C.; (Late Breaking Abstract #LB108).

We found that a polyunsaturated fatty acid (i.e., conjugated linoleic acid, CLA) was protective against dextran sodium sulfate (DSS)-induced colitis. This protective effect correlated with increased expression of both PPAR γ and δ, but not PPAR α, and it was specific for CLA but not for other polyunsaturated fatty acids (i.e., linoleic acid, LA). The objective of this study was to determine whether PPAR γ and δ contribute to protection from colitis. C57BL/6 mice received CLA or LA orally for 7 weeks and were subsequently challenged with 2.5 % DSS in drinking water for 7 days. Evaluation of PPAR γ and δ mRNA expression and transcriptional activation at the colon was performed by quantitative real-time RT-PCR, and determination of NF-κB activation by an ELISA-based method. CLA upregulated PPAR γ and δ expression, transcriptionally modulated PPAR γ and δ responsive gene clusters (UCP1, UCP3, PGC-1α, CD36, and TNF-α), and suppressed NF-κB p65 activation. Clinically, CLA ameliorated weight loss, colitis and disease activity. We conclude that both increased expression and activation of PPAR γ and δ by CLA contributed to protection from colitis.