Solving the obesity epidemic continues to stump scientists. One-third of Americans are overweight or obese, and while physicians can work to encourage patients to improve diets and physical activity, treating those who are morbidly obese is a much more difficult task.

Keeping a healthy weight and fighting off obesity comes down to maintaining energy homeostasis — or the balance between calorie intake and calorie burning. In addition to the types of foods you eat and how much you exercise, this energy balance is influenced by numerous genes, proteins, and enzymes in the body. Now, new research suggests that maintaining energy balance may have a lot to do with a specific enzyme known as O-GIcNAc transferase (OGT), which is involved in the regulation of insulin and metabolism. Published in Science, the study found that knocking out OGT in neurons in mice's brains had a huge impact on their diets and energy balance: It made them overeat significantly and gain three times as much fat tissue.

In the study, the researchers gathered mice and injected them with either a control virus or a virus that impaired the OGT function in neurons located in the hypothalamus of the brain — specifically the paraventricular nucleus (PVN). The mice that were given the OGT-inhibiting virus increased their daily food intake significantly, eating twice as much as control mice. Their fat tissue also rose sharply. Only when the researchers controlled the amount of food the mice ate, giving them as much as the control mice, did they stick to a normal weight.

“Overeating and obesity are rapidly becoming worldwide problems,” the authors wrote in the study. “Normally, mice do not overeat — they balance their caloric intake with their caloric needs.” After the researchers deleted the enzyme OGT from neurons in the mouse hypothalamus, “the animals began to overeat and rapidly gain weight,” they continued. “The animals ate more at meal times, rather than eating more often. Thus, OGT seems to regulate satiety and helps to couple caloric intake to caloric need.”

On the other hand, the research also showed that stimulating the OGT-expressing neurons in the PVN would have the opposite effect of decreasing food intake.

Currently, there are some anti-obesity drugs that work to target certain pathways in the brain involved with appetite, impulse control, and satiety. In 2015, researchers toyed with certain genes in mice that contributed to obesity. When they removed the genes, the mice converted fat cells into heat more quickly, paving the way for a new type of drug that could fight obesity. Likewise, the latest research may shed light on yet another potential form of obesity treatment, one where scientists could develop a drug to stimulate OGT expression.

Source: Lagerlöf O, Hong I, Aponte Y, Blackshaw S, Hart G.W., Huganir R.L. The nutrient sensor OGT in PVN neurons regulates feeding. Science. 2016.