Endogenous synthesis of n−3 PUFAs can reduce lipid synthesis in Fad3 transgenic cattle

n−3 polyunsaturated fatty acids (PUFAs) play important roles in the health, development and growth of mammals. However, most mammals, including humans, cannot synthesize n−6 and n−3 PUFAs and can only obtain them from the diet. The fatty acid desaturase 3 (Fad3) gene from flax encodes a fatty acid desaturase that convert n−6 PUFAs to n−3 PUFAs through desaturation at ∆15. The use of transgenic technology to produce Fad3 transgenic cattle may be an effective way for humans to obtain n−3 PUFAs. This study utilized fibroblasts derived from FAD3-transgenic and wild-type (control, CON) Luxi Yellow cattle as a model system. We systematically compared differences between the two cell groups regarding endogenous gene expression, metabolite abundance, fatty acid desaturation capacity, and lipid anabolism/catabolism pathways, aiming to elucidate how endogenous n−3 PUFAs synthesized via FAD3 regulate lipid metabolism. In Fad3 transgenic cattle, the expression of stearoyl-CoA desaturase 5 (Scd5) gene was up-regulated which promote fatty acid desaturation. Endogenously PUFAs down-regulate the expression of lipid synthesis-related genes and the activity of acetyl-CoA carboxylase (ACC), up-regulate the expression of carnitine palmitoyltransferase 1 (CPT1) enzyme, reduce lipid synthesis, increase the β-oxidation of fatty acids, and thus reduce fat deposition. In summary, the Fad3 transgenic cattle are expected to improve the nutritional value of beef, and can be used as a livestock animal model to study the beneficial effects of n−3 PUFAs.