CNR researchers, in collaboration with scientists at the Dana-Farber Cancer Institute and Harvard Medical School, have identified a natural molecular pathway that enables cells to burn off calories as heat rather than store them as fat. This raises the possibility of a new approach to treating and preventing obesity, diabetes, and other obesity-linked metabolic disorders including cancer.
Daniel Nomura, professor of Nutritional Sciences, and Toxicology, and Bruce Spiegelman, professor of cell biology and medicine at Harvard Medical School, are co-corresponding authors on the study, which appears online ahead of print in the journal Cell.
The researchers discovered the mechanism in energy-burning brown and beige fat cells in mice. They identified an enzyme, PM20D1, which is secreted by the cells and triggers the production of compounds called N-acyl amino acids. These N-acyl amino acids “uncouple” fat burning from other metabolic processes, allowing for weight loss. Such “uncouplers” were known as synthetic chemicals but this is the first known natural small molecule with uncoupling activity.
When they injected the N-acyl amino acids into obese mice which ate a high-fat diet, the researchers noted significant weight loss after eight days of treatment. The weight loss was entirely in fatty tissue.
“These data certainly suggest that either PM20D1 or N-acyl amino acids themselves might be used therapeutically for the treatment of obesity and other obesity-associated disorders” such as diabetes and fatty liver disease,” said Spiegelman.