University of Wisconsin researchers have found promising results for obesity and diabetes in a study that knocks out a gene in mice.
In a recent publication in the Proceedings of the Academy of Sciences, UW professors have shown that by removing the Stearoyl-CoA desaturase (SCD-1) gene in mice, the mice can eat a high-fat diet without gaining weight. The removal of this gene also keeps glucose levels in the body low and increases insulin sensitivity. This discovery gives high hopes to Type II diabetics.
James Ntambi, professor of biochemistry and nutritional sciences at UW, is one of the authors of the research paper that was published Aug. 20. He has been studying this type of research for about 15 years.
“There are very important implications in the research we are doing, and there is much hope in the direction of health problems related with obesity and diabetes,” Ntambi said.
The SCD-1 gene was first discovered and cloned in 1988 by Ntambi and colleagues at the Johns Hopkins University Medical School.
Recently, the SCD-1 equivalent gene in humans was discovered, and scientists can now perform the same type of tests on human tissue culture as they do in mice.
“We have been developing ways to work with human fatty tissue and determining whether the same process of removing the SCD-1 gene works as well,” Ntambi said, “So far the results are just like the rodents.”
Because of the recent news and excitement over the SCD-1 gene, the gene may become a bit of a hot spot for researchers, especially now that it is extending into human study, said research collaborator Alan Attie, professor of biochemistry at UW-Madison and co-author of the recent research publication.
The SCD-1 gene produces an enzyme that is involved in the mechanisms of weight loss. This enzyme acts as a switch: with high levels of the enzyme, more fat is deposited, and with low levels of the enzyme, more fat is burned.
In the experiments, researchers divided mice into two separate groups — a group with the SCD-1 gene removed and a control group — and fed them a diet of about 15 percent fat. The diet of a mouse is typically 5 percent fat.
Researchers said the 15 percent fat intake of mice is comparable to a 45 percent fat intake in humans.
This is an excessive amount of fat to give to rodents, and Ntambi said the results were unexpected.
“The mice lacking the SCD-1 gene did not accumulate fat; instead, their metabolic rate increased. This was illustrated in the increased oxygen consumption and reduced body fat mass,” Ntambi said. “It produced the same effects as if the mice were exercising.”
After the mice eat, glucose levels are high in both groups of mice, but levels lower significantly after a short amount of time. The control group had higher glucose levels that stayed high for a longer amount of time.
These findings indicate good news for diabetics, whose glucose levels are too high.
“This research sounds great in terms of what it can do for people affected by diabetes,” said UW-Madison junior Gordon Scott. “This research really strengthens the reputation of our university.”
Before the clinical benefits to humans can be found, some side effects need to be examined.
“We have found that an enzyme produced by the SCD-1 produces oils for skin and eyes,” Ntambi said. “So removing this enzyme causes dryness in the skin and eyes of the mice.”
Researchers hope breeding a mouse without the SCD-1 gene with a mouse that has the SCD-1 gene will create a heterozygote with half the amount of the enzyme and no side effects.
“We are still in the early experimental stage,” Attie said. “Early tests can take two to four years, and drug development can take a very long time to go through various testing stages for safety, efficacy, and questioning whether the drug is really better than anything else on the market.”
But the lab is hopeful of what is to come.
“Every drug has to start somewhere,” Ntambi said.
