Porcine peroxisome proliferator-activated receptor [delta] mediates the lipolytic effects of dietary fish oil to reduce body fat deposition

Peroxisome proliferator-activated receptor [delta] promotes fatty acid catabolism and energy expenditure in skeletal muscle and adipose tissues. A ligand for PPAR[delta] is required to activate PPAR[delta] function. Polyunsaturated fatty acids are potential ligands for PPAR[delta] activation. The current experiment was designed to determine the potential for PUFA, particularly from dietary fish oil, to activate porcine PPAR[delta] in vivo. Transgenic mice were generated to over-express porcine PPAR5 in the adipose tissue. Mice were fed a high-saturated fat (13% beef tallow), or high-unsaturated fat (13% fish oil) diet, or a diet containing 4 rag/ kg of a PPAR[delta] ligand (L165041) for 4 mo. Compared with beef tallow feeding, fish oil feeding reduced fat mass and decreased (P < 0.05) plasma triacylglycerol and FFA concentrations in the transgenic mice. Adipose tissue expression of genes involved in adipogenesis (i.e., lipoprotein lipase and adipocyte fatty acid-binding protein) was decreased in transgenic mice fed fish oil or the PPAR[delta] ligand. In the same mice, expression of the lipolytic gene, hormone-sensitive lipase was increased (P < 0.05). Fish oil feeding also stimulated expression of genes participating in fatty acid oxidation in the liver of transgenic mice compared with wild-type mice. Overall, these results indicate that PUFA may serve as natural and effective regulators of lipid catabolism in vivo and many of these effects may be generated from activation of PPAR[delta]. Key words: adipose tissue, fish oil, lipid metabolism, peroxisome proliferator-activated receptor [delta], pig, polyunsaturated fatty acid doi: 10.2527/jas.2009-2597