Researchers at Columbia University Irving Medical Center have identified thousands of molecules—produced by the genome’s “junk” DNA—that are found only in human fat cells and play an important role in how we store and use fat. The finding, published in Science Translational Medicine, could lead to better treatments for obesity and other metabolic disorders.

Knowing that humans and mice share many of the same genes, previous studies of fat regulation have relied on studies of mice. But few discoveries made in mice have been successfully translated into therapies for human metabolic disorders.

That may be because humans and mice are not as genetically similar as we thought. Although the two species share 92% of their protein-making genes, the vast majority of the genome does not code for proteins. Researchers in the past had mostly dismissed this portion of the genome as “junk” DNA with no discernible purpose.

“But more and more evidence suggests that it’s not junk at all, and parts of it are very different between humans and mice,” says Muredach Reilly, MBBCh, MSCE, director of the Irving Institute for Clinical and Translational Research at Columbia University Irving Medical Center and Florence and Herbert Irving Endowed Professor of Medicine at Columbia University Vagelos College of Physicians and Surgeons. “It raises the question: Are these parts of the genome, not found in mice, doing something in people?”

Hundreds of lincRNA molecules found in human fat cells do not exist in mice

To see if “junk” DNA plays a different role in human fat cells than in mice fat cells, Reilly’s team focused on a large portion of the genome that creates molecules called long intergenic non-coding RNAs, or lincRNAs, which evolved rapidly and are very different between mice and humans. LincRNAs were only discovered within the past decade, but it’s now known there are likely tens of thousands of them in humans.

Using unusually thorough techniques to detect RNA molecules, Reilly’s team analyzed fat tissue from 25 healthy, lean participants. Their analysis identified more than 4,000 different lincRNAs, of which 85% are not found in mice. Of these, 1,001 molecules were shared among all of the participants.

Not all lincRNAs have a function, but the researchers found signs that many of the lincRNAs unique to humans had features that suggest they also may contribute to fat regulation. The researchers took a close look at the most abundant one—linc-ADAL, which is not found in mice and had never been studied before—and found that it plays a significant role in how fat cells develop and how they store fat.

The team also discovered subsets of lincRNAs that were expressed differently in males and females and others that were expressed differently in people who had undergone bariatric surgery. These characteristics suggest potential roles for these lincRNAs in observed sex differences in fat storage as well as in obesity and its complications.