A mutation in a gene with a critical role in the brain could explain why some people are "couch potatoes" according to researchers.
Scientists in China and Scotland have made what is being called a “key discovery”, which centres on the system that regulates physical activity levels.
The teams are hopeful that the study could help "millions of patients".
Based on the findings published in the ‘PLOS Genetics’ journal, pills could be developed in the future which would motivate those who are less inclined to exercise.
While the experiments were conducted on mice, 400 overweight Chinese patients were also screened for metabolic syndrome, with scientists finding that two of them had mutations in the gene.
To make their discovery, scientists compared normal mice with those that had a mutation in a gene called SLC35D3, and found that it produces a protein which plays a key signalling role in the brain's dopamine system, affecting the regulation of physical activity.
Mice with this gene had far fewer of this type of dopamine receptor on the surfaces of their brain cells. It was instead stuck within in the cell, leaving the signal process unable to function.
But when the affected mice were treated with a drug that activates dopamine receptors, the problem was reversed and the mice became more active and lost weight.
Study leader Professor Wei Li, of the Institute of Genetics and Developmental Biology (IGDB) in Beijing, said he was excited about the findings.
“We discovered that mice with this gene mutation were typical couch potatoes,” he said.
“They walked only about a third as much as a normal mouse, and when they did move they walked more slowly.
“The mice became fat and they also developed other symptoms similar to a condition in people called metabolic syndrome - a medical term for those with a combination of risk factors related to diabetes, high blood pressure and obesity,” he explained.
He added that the discovery could signal a change in attitudes towards obesity.
"A long-standing prescription in combating obesity is to mind your mouth and move your legs. However, genetics contributes to the reluctance to move in some obese people. Medical treatments will in the future be tailored to fit a person's individual genetic make-up."
Co-author of the research paper Professor John Speakman, who works between the University of Aberdeen and the IGDB, said: "Although only about one in 200 people may have these 'rare' mutations, there are a very large number of people worldwide that have metabolic syndrome.
"Consequently, the population of sufferers that may benefit from being treated with dopamine receptor drugs runs into many millions of patients."
Additional reporting by PA