24 February 2014
ByAppeared in BioNews 743
Researchers compared mice that had a mutation in the SLC35D3 gene with normal mice, which did not have the mutation.
Although the genetically mutated mice ate the same amount of food as normal mice, they were less active and gained significantly more weight.
'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'.
The researchers then went on to show that the SLC35D3 protein is involved in normal dopamine signalling in the brain.
Dopamine is a neurotransmitter that allows electrical signals to pass between brain cells and regulates many processes, including physical activity levels.
However, in mice with the SLC35D3 mutation, the dopamine receptor accumulated within brain cells instead of being transported to the cell surface where it normally functions.
Injecting mutant mice with a drug to stimulate dopamine receptors could reverse this, and caused them to become more active and lose significantly more weight than normal mice: 13 percent compared to seven percent.
Researchers hope that this finding could lead to a treatment for obesity-related metabolic syndrome.
Yet, when the researchers screened 363 overweight or obese Chinese patients with metabolic syndrome, they only found SLC35D3 mutations in two patients.
Co-author Professor John Speakman, from the University of Aberdeen, explained: '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'.
However, it remains unclear whether these rare SLC35D3 mutations have the same effect in humans as seen in mice. It is also still unknown whether a similar dopamine enhancer will lead to weight loss in metabolic syndrome patients.