Asthma drug’s hidden metabolite converts white fat to brown fat
A study at US-based Scripps Research has highlighted a metabolite in an existing asthma drug, which seems capable of turning “bad” body fat into a more favourable one. The discovery of this latest “fat switch” opens up new therapies for obesity, ones with minimal side effects.
White fat cells are known to store excess energy in pot bellies and love handles, while brown fat cells burn away that stored energy to produce heat, helping address metabolic imbalances that can lead to conditions like obesity and diabetes.
The study at Scripps Research, along with its drug development arm Calibr, was aimed at investigating existing drug compounds that promotes the formation of one type of fat over the other. The research team eventually singled out a drug called zafirlukast, used to treat asthma.
Cell culture experiments showed that zafirlukast could turn precursor fat cells into predominantly brown fat cells, and also convert white fat cells into brown. The trouble was, however, that zafirlukast is toxic when administered in high doses, and questions remained over how exactly it was having these effects.
“We needed to use additional tools to break down the chemicals in zafirlukast’s mechanism[to] find a metabolite that was providing the same functional effect that zafirlukast was, but without the side effects,” said Kristen Johnson, PhD, Director in Translational Drug Discovery Research at Calibr.
An advanced screening method called drug-initiated activity metabolomics enabled the team to sift through thousands of metabolites to zero in on one that triggered the formation of brown fat cells, and did so without causing any harm to the cell.
The metabolite, myristoylglycine, was the only one of the thousands screened that mimics the fat-browning capabilities without the drug’s toxic effects. The metabolite is only biosynthesised upon zafirlukast treatment – thus demonstrating how naturally-occurring metabolites may be used to treat disease
