Experts at Aberdeen University, working with other researchers in a joint project in China, compared normal mice with those that had a mutation in a gene called SLC35D3.
They found that the mutation affected dopamine feel-good signals in the brain, which in turn affected the regulation of their physical activity levels.
The Chinese mice walked about one-third less than normal mice, became fat, and developed other symptoms similar to a condition in people called metabolic syndrome - a medical term for a combination of diabetes, high blood pressure and obesity.
However, when the affected mice were treated with a drug that activates dopamine receptors, they became more active and lost weight. It raises the prospect of pills tailored to couch potatoes to cure them.
Professor John Speakman, who is involved in the research, said: "There are a large number of people worldwide that have metabolic syndrome."