Conjugated linoleic acid modulates phorbol ester–induced PPAR-δ and K-FABP mRNA expression in mouse skin

Conjugated linoleic acid (CLA) inhibits mouse skin carcinogenesis. Treatment of mouse skin with the phorbol ester tetradecanoylphorbol-13-acetate (TPA) significantly increased peroxisome proliferator–activated receptor δ (PPAR-δ) mRNA expression 6 hours after treatment. When mice were fed diet with 0.5% to 1.5% CLA, TPA-induced PPAR-δ mRNA expression decreased (P < .05). In contrast, 1.5% dietary CLA significantly increased TPA-modulated PPAR-δ mRNA expression compared with acetone-treated control (P < .05) when measured 18 hours after exposure. Keratinocyte fatty acid binding protein (K-FABP) mRNA was elevated in TPA-treated mouse epidermis compared with acetone treatment, and dietary CLA significantly decreased TPA-induced K-FABP mRNA expression (P < .05). Moreover, mRNA accumulation of PPAR-δ and K-FABP was higher in mouse skin papillomas than in normal mouse epidermis, regardless of whether mice were fed CLA or when skin was exposed to different PPAR ligand treatments during the promotion stage of mouse skin tumorigenesis. Because PPAR-δ and K-FABP are involved in skin tumor promotion, the fact that CLA regulates TPA-modulated PPAR-δ and K-FABP mRNA expression may begin to explain the mechanisms of CLA for inhibiting skin cancer.