New findings establish a connection between microRNAs and cellular metabolism, suggesting that a drug designed to inhibit these tiny molecules -- once considered to be "junk" DNA -- would have a positive effect against obesity.
Tiny strands of RNA affect how our cells burn fat and sugar — a finding that gives biologists a place to start in the quest for therapies to treat obesity and related health problems, said scientists at Virginia Tech and the University of Texas Southwestern Medical Center at Dallas.
Mice on high fat diets are resistant to obesity when two mini-molecules called microRNAS are missing from their genetic makeup, according to a study this week in the Proceedings of the National Academy of Science
The discovery suggests that treatments targeting these two specific microRNAs may help stem the worldwide obesity epidemic. More than 40 million children under 5 were overweight in 2010, according to the World Health Organization, and an estimated 500 million adults were considered obese in 2008.
In the United States in 2009-2010, more than 78 million adults and about 12.5 million children and adolescents were obese, increasing their risk for type 2 diabetes, heart disease, stroke, liver disease, and some cancers, according to the National Institutes of Health.
"Scientists know the best health solution for obesity involves eating less and exercising more," said Matthew W. Hulver, Ph.D., an associate professor with the Department of Human Nutrition, Foods, and Exercise in the College of Agriculture and Life Sciences at Virginia Tech. "But in cases when people can't or won't exercise, if we can identify what is contributing to the regulation of our metabolic circuits, we can target it with a drug or pharmacologic solution."
Once considered to be little more than scrap DNA, scientists now know microRNAs have an important role in regulating how genes shape human health and behavior. They have been linked to heart disease, diabetes, hepatitis C, leukemia, lymphoma, and breast cancer.
Although microRNAs previously have been linked to obesity, the new findings are the first to establish a connection between microRNAs and cellular metabolism.
MicroRNA biologists at UT Southwestern Medical Center modified mice to be genetically unable to produce microRNA-378 and its cousin miR-378*, resulting in relatively trim animals with metabolisms that quickly convert cellular food into energy.
"We did not know the function of this pair of microRNAs, but were intrigued because they arose from a gene connected with metabolism, and they are expressed in a variety of tissues, such as muscle, fat, and liver," said Eric N. Olson, Ph.D., a professor and the chairman of molecular biology at UT Southwestern and senior author of the study. "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 litter mates. 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."