Possible Breakthrough in the Battle of the Bulge

An epidemic of obesity plagues us to an ever greater degree, despite huge efforts to combat it. Researchers at The Johns Hopkins School of Medicine reported last Spring in Science magazine, on an important discovery in mice that may be a breakthrough in this battle. The team of researchers led by Franicis Kuhajda found that inhibitors of an enzyme called fatty acid synthase (FAS), reduced food intake dramatically in mice. FAS builds fatty acids from small molecular pieces called malonyl. The mice treated with the blockers of this enzyme stopped eating, but their metabolism and activity did not decrease as would be expected if they had simply not been fed. The treated mice lost 45% more weight than the mice who were starved. So the enzyme blockers, called cerulin and C75, do not work by blocking fat production in fat cells per se, but instead by signaling the brain. Cerulin is toxic, but C75, a drug they synthesized by design, caused no untoward effects in any of the mice over the 2 week trials. Editorials about these findings in the medical literature urge caution. The last breakthrough in research on obesity found Leptin deficiency as the cause of obesity in genetically obese mice but proved to be a disappointment. There are very few obese humans who have a defect in Leptin production. But these studies do help to convince doctors that obesity is not caused by overeating and under-exercising. Those simplistic ideas have informed the traditional approach - blame the victim. If instead, we look in the right places, we may be close to an effective treatment of obesity.


Loftus TM,...,Kuhajda FP.Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors.Science 2000 288:2379-81.