COUP-TFII plays key role in control of obesity, diabetes risk
By Ruth SoRelle, M.P.H.
For decades, Ming-Jer Tsai, Ph.D., and Sophia Tsai, Ph.D, have teased out the secrets of COUP-TFII (Chick Ovalbumin Upstream Promoter Transcription Factor II), a protein that plays a key role in development and organ formation. However, the factor had a secret that they only recently unraveled.
COUP-TFII plays a key role in the control of obesity and development of diabetes, said the two researchers from Baylor College of Medicine. A report on their work appeared in a recent issue of the journal Cell Metabolism.
Leaner mice
Only when the Tsais, professors of molecular and cellular biology at BCM, bred mice that had only one copy of the gene carrying the DNA code for the factor did they find that the animals had smaller fat cells and increased energy metabolism as well as enhanced response to insulin.
"If a mouse loses one copy of the gene, the animal becomes lean," said Ming-Jer Tsai. "It is more sensitive to the effects of insulin and resistant to obesity from a high fat diet."
The animals not only have less fat, they also have more muscle and burn more energy, he said.
Potential drug target
Their studies raise the likely possibility that one can use COUP-TFII as a potential target for diabetes and obesity drug treatment. In fact, identifying a drug that could reduce the effect of COUP-TFII activity has become a future focus for their research, said Sophia Tsai.
"We don't need to inhibit it totally," she said. "Partial inhibition will do the trick as when you lose one copy of the gene, your fat cells are already much smaller and the animal is lean."
Drs. Luoping Li and Xin Xie, postdoctoral associates in Dr. Tsai's laboratory were major contributors to the work. Others who took part include Jun Qin, George S. Jeha, Pradip K. Saha, Jun Yan, Claire Menoza Haueter and Lawrence Chan, all of BCM.
Funding for this research came from the National Institutes of Health and the Baylor Diabetes and Endocrinology Research Center funded by the National Institute of Diabetes and Digestive and Kidney Diseases at BCM.
