Krude's group first identified the same gene variant in a small group of 15 obese children. They then extended the study to include 722 obese children and adolescents and uncovered the mutation in two people.
Although rats do not normally produce -MSH, previous studies indicated that the animals respond to the administered hormone by eating less. Krude's team now reports that the mutant version of the hormone failed to reduce food intake in animals, consistent with its link to increased obesity risk.
"The findings tell us that human body weight regulation is particularly dependent not only on α-MSH, but also on -MSH," Krude said.
"Our studies show that even subtle changes in POMC can lead to obesity, and that the potential role for -MSH had been unfairly neglected," O'Rahilly added. "The findings add weight to the notion that drugs that target the melanocortin system might be beneficial in the treatment of obesity."
After the discovery that α-MSH played a significant role in energy balance, there were many efforts to develop a drug that would mimic the hormone, Krude said. While studies confirmed that the drugs did reduce body weight and food intake in animals and people, they came with an unfortunate side effect, he said. They also induced sexual behavior.
"It became clear that drugs based on α-MSH could not be used on an everyday basis to treat disorders of body weight," Krude said. "It was a big disappointment. Now there is hope that -MSH might work better."