Study of asthma drug uncovers metabolite that switches bad fat to good
The authors have pinpointed a metabolite that turns a bad type of fat into a more favorable one, which raises hoped of new therapies for obesity with minimal side effects.
Carried out at Scripps Research, the new study centers on the difference between white fat and brown fat in the human body, and the metabolic processes that promotes one type over the other. White fat cells store excess energy in pot bellies and love handle
s, while brown fat cells burns away that stored energy to produce heat, helping address metabolic imbalances that can lead to conditions like obesity and diabetes.
We are seeing scientists make promising inroads into potential therapies that promote the formation of brown fat over white fat, or even convert one into the other like a “fat switch.” For the Scripps Research team, this pursuit led them to examine a catalog of existing drug compounds already tested for human safety. Advanced screening methods led them to one with some exciting potential, an FDA-approved asthma drug called zafirlukast.
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,” says Kristen Johnson co-senior author of the study. “Framed another way, could we find a metabolite that was providing the same functional effect that zafirlukast was, but without the side effects?”
Another advanced screening method called drug-initiated activity metabolomics provided the scientists with some answers. It enabled them 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.