What is the connection between the protein that regulates the development of an embryo in cows and sheep and the prevention of chronic inflammatory diseases in humans?
To answer that question, let’s go back to 2003, when Fuller Bazer, distinguished professor of animal science at Texas A&M University and Michael Roberts, curator’s professor of animal science at the University of Missouri were awarded the prestigious Wolf Prize for their discoveries of interferon tau (IFNT) and other pregnancy-associated proteins during their 17-year collaboration while at the University of Florida.
As Bazer explained, it was a well-known fact that communication between the embryo and mother was critical for successful pregnancies in mammals, but no one knew the ‘pregnancy signal’. “The details of how the process worked or what molecules were responsible for regulating embryo development and fetal growth in domestic animals hadn’t been discovered,” said Bazer. “Once we identified the protein secreted by the embryo into the uterus as IFNT, we were able to make sure that the corpus luteum on the ovary stayed functional in producing the progesterone needed to maintain a pregnancy in livestock.”
Having discovered the new IFNT protein, Bazer proceeded to learn about the properties of interferons. “For example, interferon alpha was being used to treat people with diseases such as hepatitis, but those people suffered many undesirable side effects,” Bazer explained. “That was due to the cytoxicity of that interferon. Being treated with interferon alpha daily is like having the flu every day for many months; first you get fever, loss of appetite and GI problems which can ultimately lead to anorexia, dementia and so forth.”
“I knew from our experiments that the sheep conceptus (embryos and their membranes) produce very high amounts of IFNT and that it was not having cytoxic effects on the cells in the uterus. It wasn’t making the sheep sick, which was highly significant,” he continued. Cytoxicity is due to inflammatory effects and since the uterus did not show evidence for inflammation, I reasoned that IFNT must either not affect inflammation or even be anti-inflammatory.”
Bazer and his team at Texas A&M began testing his hypothesis.
“We checked cytoxicity in the blood cells of cats infected with feline immunodeficiency virus and confirmed that IFNT was significantly less cytotoxic than interferon alpha,” Bazer continued. “Then we tested it further by treating animal models for inflammatory diseases like diabetes, multiple sclerosis and other diseases caused by an inflammatory state. We were able to confirm that IFNT, administered orally, actually slowed the progression of those diseases.”
But how IFNT reduced inflammation and halted the adverse effects of these diseases remained unknown.
Bazer and his multi-disciplinary team combined their expertise in biology, nutrition, physiology and pharmacology to focus on the link between inflammation, obesity and the anti-inflammatory properties of IFNT and apply them to the challenge of reducing obesity and the risk for obesity-induced inflammation and metabolic syndrome.
Why? Because obesity is a worldwide epidemic resulting from a chronic imbalance between food energy intake and whole-body energy expenditure, as well as inflammation and oxidative stress. Obesity contributes to adverse health outcomes known collectively as metabolic syndrome that includes insulin resistance, type 2 diabetes mellitus, obstructive sleep apnea, osteoarthritis, stroke, hypertension, cardiovascular disease, atherosclerosis, and certain types of cancer, such as colon and breast cancers.
What if Bazer’s team can come up with an oral medication using INFT that reduces obesity and all the diseases it can cause?
Bazer described the process: “We use the Zucker Diabetic Fatty (ZDF) Rat for studies of effects of IFNT on obesity and time of onset of type 2 diabetes. These rats are bred to get fat and develop type 2 diabetes and we wanted to know if IFNT could reduce the amount of white (bad) fat and increase the amount of brown (good) fat in the ZDF rats.
The results were exciting; the IFNT-treated ZDF rats exhibited a 40 percent decrease in white fat and a 46 percent increase in beneficial brown fat, which corresponded to an increase in whole-body energy expenditure, improved metabolic status and reduced oxidative stress. In other words, the IFNT corrected the imbalance that causes obesity and obesity-related diseases.
Similar positive results occurred when the team used non-obese diabetic mice. Orally ingested IFNT was found to delay the onset of diabetes, and prolong sensitivity to insulin in the mice models of diabetes.
Fuller Bazer is one of the university’s treasures. Despite his passion for research, especially in his chosen field of reproductive biology, since joining the faculty in 1992 as Professor and O.D. Butler Chair in the Department of Animal Science, he has answered the call to serve in many high-level administrative positions, including Associate Vice Chancellor for Agriculture and Life Sciences, Executive Associate Dean of the College of Agriculture and Life Sciences, Associate Director of the Texas Agricultural Experiment Station (2001-2004), Associate Vice President for Research (2005-2008) and Interim Head of Veterinary Pathobiology (2009-2010).
He has also been the recipient of numerous highly regarded awards, including the aforementioned Wolf Prize for Agriculture in 2003, the Alexander von Humboldt Research Award in Agriculture, the Society for the Study of Reproductive Biology Carl Hartman Award and The Association of Former Students Distinguished Achievement Award in Research.
Now, finally able to work full-time on his research, Bazer still has some questions he needs answered and some important contributions to make. He and his research team are dedicated to finding practical applications for the interferon tau protein he discovered years ago – like developing an oral medication to prevent obesity and obesity-related diseases in humans. It’s only a matter of time.
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For more information regarding news from the Department of Animal Science, College of Agriculture and Life Sciences, Texas A&M University, please contact Courtney Coufal at cacoufal@tamu.edu or (979) 845-1542.