MicroRNAs jumpstart production of obesity-fighting brown fat

CAMBRIDGE, Mass. – With each passing day, America is getting fatter.  Unfortunately, we’re gaining the wrong type of fat: potentially harmful white fat, which stores energy as lipids around our midsections, rather than helpful brown fat, which burns those lipids and generates heat in response to a cold environment.

Because brown fat gobbles up lipids as fuel, scientists are seeking to fight obesity by increasing the small brown fat pockets deposited in the neck, along the shoulders, and down the spine in adult humans. Studies in mice and humans have shown that an increase of brown fat in the body is associated with increased resistance to obesity and its related diseases, including diabetes and cardiovascular disease. The problem, however, has been finding a viable approach to stimulating brown fat production that doesn’t merely involve prolonged exposure to cold environments.

In a paper published July 10 on the Nature Cell Biology website, Whitehead Institute scientists report finding the first microRNAs (miRs) that regulate the development of brown fat. miRs are tiny bits of RNA that fine-tune gene expression. In this case, the identified cluster of miRs—known as miR-193b-365— enhances brown fat formation in vitro by reducing the expression of certain genes in muscle/brown fat precursor cells.

“It’s remarkable that a 21-nucleotide RNA can divert a cell from becoming a muscle cell and turn it into a brown fat cell,” says Whitehead Founding Member Harvey Lodish. “And we’re beginning to understand in some detail how this happens.”

In their paper, co-authors Lei Sun and Huangming Xie describe for the first time the cellular network that determines whether a precursor cell becomes a muscle cell or brown fat cell and miR-193b-365’s role in this network.

“Before, we knew a single molecule, called Prdm16, that was involved in this determination process, but we now understand a network of this process,” says Xie, who is a former graduate student in the Lodish lab. “This network is not complete, but it’s one important step further.”

By understanding the network’s complexity better, Sun says he hopes to find a treatment that bypasses miRs completely, as the tiny RNAs are notoriously difficult to work with in a clinical setting. 

“Which miR targets mediate brown fat development?” asks Sun, who is a postdoctoral researcher in the Lodish lab. “If you can identify the miRs’ targets, then in the future, you could directly manipulate those targets with drugs and reduce obesity.”

This research was supported by the National Institutes of Health (NIH) and the Singapore-MIT Alliance (SMA).

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Harvey Lodish’s primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a professor of biology and a professor of bioengineering at Massachusetts Institute of Technology.

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Sun, L. et al. “miR-193b-365 is essential for brown fat differentiation." Nature Cell Biology, online July 10, 2011.