Experimental drug suppresses obesity development by terminating fat-producing stem cells

Working on the origins of metabolic disease from the left are UTHealth researchers Qingchun Tong, Ph.D., Alexes Daquinag, Ph.D., and Mikhail Kolonin, Ph.D.

The drug prototype named D-WAT hones in on the unhealthy or white fat that rings the waists of many Americans and prevents its accumulation, the scientists report. It appears that this molecule also changes the remaining white fat for the better.

  Working on the origins of metabolic disease from the left are UTHealth researchers Qingchun Tong, Ph.D., Alexes Daquinag, Ph.D., and Mikhail Kolonin, Ph.D.

There are two main types of fat. The body uses brown fat to stay warm and metabolically active; whereas, white fat builds up in the body and may cause health issues.

“We’re trying to strike the right balance between the white fat and brown fat,” said Mikhail Kolonin, Ph.D., the study’s senior author and holder of the Harry E. Bovay, Jr. Distinguished University Chair in Metabolic Disease Research at the UTHealth Medical School. “You need both.”

To strike that balance, Kolonin and colleagues developed D-WAT, which targets stem cells that give rise to white fat cells (adipocytes). This compound consists of a component that can find white fat stem cells and a component that destroys them.

In the preclinical study, the researchers demonstrated they could suppress the growth of white fat by reducing the number of white fat stem cells. In addition, they observed the appearance of brown adipocytes in white fat tissue.

“We were surprised to learn that the remaining white fat became more brown,” said Alexes Daquinag, Ph.D., lead author and senior research scientist at the UTHealth Medical School.  “We discovered that in response to treatment, a distinct population of stem cells became activated and gave rise to brown adipocytes. As a result of that, mice became more active and burned more calories.”

Another benefit of the drug, according to Kolonin, is that it appears to be long lasting. While there are other drugs that convert white fat into brown fat tissue, their effects are temporary, Kolonin said.

“Our study potentially provides an approach for the sustained activation of brown fat; although, additional tests are needed in advance of clinical trials.” said Kolonin, who directs the Center for Metabolic and Degenerative Diseases at the UTHealth Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases. The D-WAT technology and associated patents are licensed to Astrotide Inc.

More than 78 million adults in the United States are obese, resulting in increased risk of heart disease, stroke, Type 2 diabetes and other conditions, according to the Centers for Disease Control and Prevention.

Not limited to obesity prevention, the compound may also be helpful in the treatment of cancer, Kolonin said. “In previous studies in our laboratory, we found that the white adipose stem cells help the growth of tumors.  And it stands to reason that destroying the white adipose stem cells may actually prevent the growth of cancer,” Kolonin said.

Other UTHealth researchers involved in the study include graduate research assistant Chieh Tseng, postdoctoral research fellow Ahmad Salameh, Ph.D., senior research assistant Ali Dadbin, instructor Yuanzhong Xu, Ph.D., and associate professor and Becker Family Foundation Professor in Diabetes Research Qingchun Tong, Ph.D.

Kolonin and Tong are on the faculty of The University of Texas Graduate School of Biomedical Sciences at Houston, which is operated jointly by UTHealth and The University of Texas MD Anderson Cancer Center. Tseng is enrolled in the school.

The study titled “Depletion of white adipocyte progenitors induces beige adipocyte differentiation and suppresses obesity development” received support from the American Heart Association and the Cancer Prevention & Research Institute of Texas.

Rob Cahill
Media Hotline: 713-500-3030

Categories Obesity