Fat chance? An enzyme called SCD1 may be a promising drug target.

New Weapon in Fat Offensive?

There may be new hope for people who tried everything--from high, fat-low carb regimes to the low-fat grapefruit plans--but cannot lose weight. Researchers working with mice have shown that reducing the activity of an enzyme involved in making fat can prevent animals from gaining weight even on a high fat diet.

An enzyme called Stearoyl-CoA desaturase-1 (SCD1) plays an important role in fat production by helping to convert saturated fatty acids into monounsaturated fatty acids, the building blocks of triglycerides. Triglycerides are fatty substances in the blood that store energy, and high triglyceride levels are known to increase chances of heart disease. To shut down fat production, scientists have experimented with eliminating SCD1 entirely in mice by knocking out the gene that encodes it, and that does work--but also causes hair loss.

Biologist Bei Zhang and her team of scientists at Merck Research Laboratories in Rahway, New Jersey, wanted to see what would happen if they slowed down SCD1 activity in mice. Zhang put mice on a diet made up of 60% fat, and injected them twice a week with a molecule that binds to SCD1 messenger RNA and keep it from processing fat. Over 10 weeks, injected mice ate the same amount of food as untreated mice, yet they lost weight and became leaner.

Zhang found that SCD1 activity was reduced by 60-90%. Fatty acids in the blood, liver and fat-storing tissues were also significantly reduced. Further, the mice were more physically active and resting energy expenditure rose by 12%, indicating that overall metabolism had increased. Since the mice didn't experience any hair loss and no adverse side effects were observed, the work suggests that SCD1 could be a good drug target for controlling obesity in people, the team reports in the 10 March online advance publication of the Journal of Clinical Investigation.

It's important to keep the finding in perspective, cautions Roger Unger of the University of Texas Southwestern Medical Center in Dallas. The team demonstrated that reducing SCD1 activity can prevent obesity--but they haven't show yet that it will help the already obese to lose weight, he says.

Related Sites
Flier's Web site
Unger's Web site