Industry-Sponsored Research Week

Merck-sponsored research at U of Utah finds new target to treat pre-diabetes


By David Schwartz
Published: July 9th, 2019

A category of fatty lipids called ceramides are so important to metabolic health that they may well be “the next cholesterol,” says University of Utah professor Scott Summers, PhD. Summers led a just-published study in Science suggesting that targeting ceramides could reverse insulin resistance and fatty liver — both major risk factors for diabetes and heart disease.

Collaborating with scientists at Merck Research Laboratories, which is sponsoring the research, Summers and his colleagues developed a technique for lowering the amount of ceramides in the body by switching off an enzyme called dihydroceramide desaturase 1 (DES1).

In a mouse model, the chemical change prevented pre-diabetes among those given a high-fat diet, and it reversed it in obese mice. Summers is now working with co-author David Kelley, MD, a former Merck scientist, to develop drugs that can achieve the same chemical shift.

Previous research in Summers’ lab had shown that reducing ceramides could prevent metabolic disorders, but targeting the lipids directly caused dangerous side effects. So they tried deactivating DES1 in genetically engineered mice using two techniques: either turning off the gene that makes the enzyme, effectively removing it from the body, or deleting the enzyme only in liver or fat cells.

Both techniques worked, despite the fact that the mice didn’t lose weight during the two-month study period. Still, their livers cleared out excess fat and the mice responded to insulin and glucose just as healthy, skinny animals would.

“Their weight didn’t change but the way they handled nutrients did,” Summers said in the statement. “The mice were fat but they were happy and healthy.”

Researchers theorize that ceramides stiffen the cell membrane and promote fat storage, which helps prevent cells from rupturing. In the skin, ceramides help maintain a barrier against pathogens, but their downside is that obesity keeps ceramide levels high, which can cause insulin resistance and fatty liver disease.

Summers’ team is now working on determining the long-term effect of lowering ceramides in mice. The potential effect in humans is still unknown.

Source:  Fierce Biotech

Posted under: University-Industry Engagement Week

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