Subtract A Gene And Feasting Mice Add No Fat

Writing in the online editions of the Proceedings of the National Academy of Sciences (PNAS), James M. Ntambi, a professor of biochemistry and of nutritional sciences at the University of Wisconsin-Madison and colleagues report that mice lacking a gene known as SCD-1 can eat a rich high-fat diet and avoid the consequences of fat deposition and excess sugar in the blood, the hallmark of type II diabetes.

The new finding, says Ntambi, provides insight into the central genetic mechanisms that underpin diet and metabolism, and suggests it may one day be possible to devise drugs to effectively protect against obesity and diabetes. The gene SCD-1 produces an enzyme known as SCD that is required for the body to make the major fatty acids that reside in fat tissue.

Ntambi, who collaborated in the study with Alan Attie a professor of biochemistry at UW-Madison and Jeffrey M. Friedman, a Howard Hughes Medical Institute investigator at Rockefeller University, says the mice lacking the SCD-1 gene defied every attempt to make them fat.

"The idea was to make them fat," Ntambi says, "but the mice lacking the SCD-1 gene never got up there despite a diet that contained nearly 15 percent fat. What we found is that when you feed these animals a high-fat diet for several weeks, they fail to accumulate fat over time."

The effect, according to the PNAS report, seems to be systemic. In the mice lacking the SCD-1 gene, fat does not accumulate in the liver or other tissues where, under normal circumstances, it would gather and contribute to health problems typically associated with diet and obesity, says Ntambi.

Instead, the excess fat seems to be metabolized: "We have biochemical evidence that the mice burn the excess fat," says Ntambi. "The protection from obesity involves increased energy expenditure and increased oxygen consumption."

Attie says that while the surface effects of removing the SCD-1 gene are not entirely unique, it is notable that the model provides a glimpse of the metabolic mechanisms that underpin those effects: "The fact that you're increasing metabolic rate as a result (of knocking out the gene and its enzyme products) is really interesting."

He notes that while the mice are more insulin sensitive, further tests will be needed to see if they are indeed protected from diabetes. But the absence of the SCD-1 gene does keep glucose levels in the blood low. Diabetes is characterized by a deficiency of insulin and high levels of sugar in the blood.

"These animals are more insulin sensitive and don't become diabetic," Ntambi say