Off-switch for overeating and obesity found in the brain

Littermates were injected with either a control virus (right) or a virus that knocked out O-GlcNAcTransferase (OGT) (left) in a subpopulation of cells in the hypothalamus in the brain. The OGT knockout made the mouse eat twice as much as its sibling. This photo was taken about five weeks after virus injection. (credit: Olof Lagerlof)

After tediously tracking calories and willfully shunning cravings, many a dieter has likely dreamt of a simple switch that, when thrown, could shut down hunger and melt away pounds—and scientists may have just found it.

When researchers knocked down a single enzyme in the brains of mice, the rodents seemed to lose the ability to tell when they were full. They ate more than twice their usual amount of food at meal times and tripled their body fat within three weeks. And—most strikingly—when the researchers reversed the experiment, the mice just as quickly stopped eating so much. Data on the enzymatic switch, published Thursday in Science, suggests a possible target for future drugs to treat obesity in humans.

The enzyme is O-GlcNAc transferase, or OGT, which is known to work in a chemical pathway controlled by nutrients and metabolic hormones, particularly insulin. That pathway has long been linked with obesity. But researchers knew almost nothing about how the pathway linked to the metabolic disorder or OGT’s specific role.