Co-expression of fat1 and fat2 in transgenic pigs promotes synthesis of polyunsaturated fatty acids.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are essential for the development and health of mammals， such as humans and livestock. n-3 PUFAs must be supplied by diet due to the absence of a key gene， namely， delta-15 desaturase (fat1)， which is responsible for synthesizing n-3 PUFAs from a major type of n-6 PUFAs， linoleic acid (LA). To increase the dietary intake of n-3 PUFAs for humans， fat1-expressing transgenic (TG) livestock have been produced to provide n-3 PUFA-rich meats for humans. However， these TG livestock synthesized n-3 PUFAs from diet-derived， instead of endogenously produced， n-6 PUFAs because they still lack the delta-12 desaturase (fat2) gene for catalyzing conversion of internal oleic acid (OA) to LA. To fill the gap in the de novo n-3 PUFA biosynthesis pathway and to increase n-3 PUFA content in livestock， TG pigs co-expressing fat1-fat2 were generated in the present work. The OA content decreased in fat1-fat2 TG pigs， suggesting that OA was converted to LA by fat2 transgene-encoded delta-12 desaturase. The n-3 PUFA level was elevated， and the n-6/n-3 PUFA ratio dropped in fat1-fat2 TG pigs， revealing that fat1 transgene promoted the synthesis of n-3 PUFAs from n-6 analogs. The expression levels of fatty acid elongase-5 (ELOVL5) and fatty acid elongase-2 (ELOVL2)， which are two key enzyme genes for PUFA synthesis， as well as their transcription factor peroxisome proliferator-activated receptor α， increased in fat1-fat2 TG pigs. Thus， the fat1 transgene enhanced n-3 PUFA synthesis by upregulating the expression of enzyme genes involved in the PUFA synthesis pathways. Overall， this study provided a new strategy to produce n-3 PUFA-rich meat for human consumption. The generated fat1-fat2 TG pigs can also serve as a large animal model for studying the roles of n-3 PUFAs in human development and health.