Two microRNAs have been identified as potential therapeutic targets for obesity. Researchers at Virginia Tech and the University of Texas Southwestern Medical Center at Dallas have shown that mice genetically engineered to lack microRNA-378 (miR-378) and miR-378* are remarkably resistant to obesity when fed a high-fat diet, and are metabolically more capable of converting food into energy than wild-type littermates.
The team’s studies, reported in PNAS, also showed that liver and skeletal muscle mitochondria from the engineered mice exhibited increased levels of oxidation, indicating that loss of the two microRNAs is linked with increased energy expenditure and resistance to obesity. “We did not know the function of this pair of microRNAs, but were intrigued because they arose from a gene connected with metabolism, and are expressed in a variety of tissues, such as muscle, fat, and liver,” explains senior author Eric N. Olson, Ph.D., professor and chairman of molecular biology at UT Southwestern.
“When we modified mice so that they were missing these microRNAs, it permitted their cells to burn more energy and have greater obesity resistance than those of their untreated littermates. This pair of microRNAs seems to function as key regulators of metabolism, suggesting that a drug designed to inhibit them would have a positive effect against obesity.”
The microRNA IP has been licensed by the UT Soutwestern Medical Center to Miragen Therapeutics, and is currently at the lead optimization stage. The partners have also established a multiyear Sponsored Research Agreement through which Miragen hold exclusive rights to license all future microRNA-related discoveries from Dr. Olson’s laboratory.