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Apr 24, 2013

miRNA: The Key to Losing Those Love Handles?

  • Can white fat cells be converted into brown fat cells to melt away excess pounds? Researchers now say they’ve come a step closer to this dream: They decoded a “toggle switch” in mice which can significantly stimulate fat burning.

    All fat is not alike. Love handles in particular contain troublesome white fat cells, which store excess food. Brown fat cells are the exact opposite: They burn excess energy as the desirable “heaters” of the body. Scientists at the University of Bonn working with Alexander Pfeifer, Ph.D., director of the Institute for Pharmacology and Toxicology, have spent years using animal models to explore how white fat can be converted into brown fat. “In this way, excess pounds may be able to simply be melted away and obesity combated,” says Prof. Pfeifer.

    The researchers have now decoded a microRNA switch in mice that is important for brown fat cells. The researchers specifically studied microRNA 155. This gene regulator inhibits the transcription factor CCAAT/enhancer-binding protein β, which controls brown fat cell function.

    Surprisingly, Prof. Pfeifer and his team found that this transcription factor also regulates the levels of microRNA 155, establishing a tight feed-back loop that works like a toggle switch: When the microRNA is highly expressed, brown fat cell differentiation is blocked; conversely, if the transcription factor wins the upper hand, brown fat is produced at an increased level, and this in turn boosts fat burning in the body.

    The researchers at Bonn University and their colleagues from Germany’s Federal Institute of Drugs and Medical Devices and from the University of Regensburg worked with so-called transgenic and knockout mice in which the gene for microRNA 155 was either increased or silenced. “The mechanism was already set in motion when the microRNA 155 was only halved in the mice,” reports lead author Yong Chen, graduate student of the NRW International Graduate School Biotech-Pharma. The mice then had significantly more brown fat cells available than did the control group, and had even converted white fat cells into brown fat cells.

    The microRNA functions as an antagonist to the brown fat cells. “As long as enough microRNA 155 is present, the production of brown fat cells is blocked,” says Chen. Only if it falls below a certain proportion does this brake let up; the blueprint for brown fat can be read and implemented by the cell—the desired fat burners can develop. The team says these findings help scientists better understand the causes of lipid metabolism diseases.

    The researchers see in their results a potential starting point for drugs to combat obesity. They have clues to the fact that the results, if anything, can be transferred from mice to humans. Thus, for example, researchers in Leipzig found increased levels of microRNA 155 in significantly overweight patients. This corresponds to findings from animal models: A lot of microRNA 155 is associated with reduced fat burning. “However, we are still in the basic research stage,” says Prof. Pfeifer. The path to suitable drugs is still a long one, he says.

    The results appear in Nature Communications in a paper titled “miR-155 regulates differentiation of brown and beige adipocytes via a bistable circuit”.


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