Abundant expression of uncoupling protein-2 in the small intestine: up-regulation by dietary fish oil and fibrates

Mitochondrial uncoupling protein-2 (UCP-2) is widely expressed in various mammalian tissues, although its physiological functions are not well understood. We examined the effects of dietary fish oil on UCP-2 expression in the rat small intestine, in which UCP-2 mRNA levels are higher than in other organs. Feeding with fish oil (20%) up-regulated UCP-2 mRNA within 6 days in the small intestine as well as the liver, compared to feeding with soybean oil. This was mimicked by feeding with agonists for peroxisome proliferator-activated receptor α (PPARα) such as fenofibrate and bezafibrate, but not the PPARγ agonist troglitazone. The bezafibrate-induced increase in UCP-2 expression was found within 2 days in the small intestine, but only after 6 days in the liver. The up-regulation of UCP-2 was also found in cultured intestinal epithelial cells (IEC-6) treated for 24 h with various long-chain fatty acids and PPARα agonists. These results indicated that intestinal UCP-2 is up-regulated through direct activation of PPARα by dietary fatty acids.