Researchers report they have created pigs that produce omega-3 fatty acids, which are known to improve heart function and help reduce the risks for heart disease, representing the first cloned transgenic livestock in the world that can make the beneficial compound. The research could be a boost to both farmers and health-conscious consumers seeking an alternative and safer source of omega-3 fatty acids. Currently, the only way for humans to realize the benefits of omega-3 fatty acids is by taking dietary supplements or by eating certain types of fish that may also contain high levels of mercury.
The results, which are being published by Nature Biotechnology, are the work of a team assembled by Yifan Dai, M.D., Ph.D., of the University of Pittsburgh School of Medicine that includes researchers from Randy Prather, Ph.D.'s group at the University of Missouri-Columbia (MU) National Swine Resource and Research Center, the laboratory of Jing X. Kang, M.D., Ph.D., at Massachusetts General Hospital (MGH), and the laboratories of Dr. Dai and Rhobert Evans, Ph.D., at the University of Pittsburgh.
To stimulate production of omega-3 fatty acids in pigs, a team led by Dr. Dai transferred a gene known as fat-1 to pig primary fetal fibroblasts, the cells that give rise to connective tissue. Dr. Prather's group then created the transgenic pigs from these cells using a method called nuclear transfer cloning. The transgenic pig tissues were then analyzed for omega-3 fatty acids in Dr. Kang's lab at MGH and by Drs. Dai and Evans at Pitt. The fat-1 gene is responsible for creating an enzyme that converts less desirable, but more abundant, omega-6 fatty acids in the animals to omega-3 fatty acids. The results could lead to a better understanding of cardiovascular function not only in pigs, but in humans as well.
"Pigs and humans have a similar physiology," said Dr. Prather, distinguished professor of reproductive biology in MU's College of Agriculture, Food and Natural Resources and a corresponding author with Dr. Dai. "We could use these animals as a model to see what happens to heart health if we increase the omega-3 levels in the body. It could allow us to see how that helps cardiovascular function. If these animals are put into the food chain, there could be other potential benefits. First, the pigs could have better cardiovascular function and therefore live longer, which would limit livestock loss for farmers. Second, they could be healthier animals for human consumption."
"While fish, especially salmon and tuna, is one of the best food sources of omega-3 fatty acids, we have been warned to limit consumption because of high mercury levels. These animals could represent an alternative source as well as be an ideal model for studying cardiovascular disease and autoimmune disorders," said Dr. Dai, an associate professor of surgery at the University of Pittsburgh School of Medicine's Thomas E. Starzl Transplantation Institute.
"Livestock with a health ratio of omega-3 to omega-6 fatty acids may be a promising way to re-balance the modern diet without relying solely on diminishing fish supplies or supplements," Dr. Kang said.
The transgenic pigs were created using technology developed by Dr. Kang of MGH, an associate professor of medicine at Harvard Medical School and co-lead author of the current report with MU's Liangxue Lai, Ph.D. Dr. Kang's group created the first omega-3 rich mammals (mice) and published that work in Nature in 2004. Because of this earlier study, Dr. Dai initiated the collaboration with the aim of creating cloned transgenic pigs capable of making omega-3 fatty acids.
The production of these pigs will now provide researchers with opportunities to conduct studies not previously possible. For example, researchers in MU's College of Veterinary Medicine department of biomedical sciences now plan to study the omega-3 pigs. Harold Laughlin, Ph.D., department chair, uses pigs to study the cardiovascular benefits of exercise because a pig's cardiovascular system is similar to a human's. Now he plans to incorporate these unique pigs into his research to determine how higher omega-3 levels and exercise could affect the cardiovascular system.
In addition to Drs. Prather and Lai at MU, Dr. Kang at MGH and Drs. Dai and Evans at Pitt, other authors include Rongfeng Li, Ph.D., Hwan Yul Yong, Ph.D., Yanhong Ho, Ph.D., David M. Wax, Clifton N. Murphy, Ph.D., D.V.M., August Rieke, M.S., Melissa Samuel, Michael L. Lihville, D.V.M., and Scott W. Korte, D.V.M., all of MU; Jingdong Wang of MGH and Harvard Medical School; and William T. Witt, M.S., and Thomas E. Starzl, M.D., Ph.D., of the University of Pittsburgh.
Their research was supported by the National Institutes of Health, the American Cancer Society and an unrestricted gift to the Thomas E. Starzl Transplantation Institute at the University of Pittsburgh from the Robert E. Eberly Program for Transplant Innovation.
The findings will appear in the April 6 issue of Nature Biotechnology.
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