How brown adipose tissue can be activated
A team of ETH-Zurich researchers headed by Markus Stoffel has discovered a signaling molecule that activates brown adipocytes and increases their formation. This knowledge could help overweight people to burn their excess white fat.
Infants have a very special kind of cell in their delightful baby fat: brown adipocytes. These form contiguous tissue on the neck, along the breastbone and between the shoulders. Around five per cent of their body weight is brown adipose tissue – and with good reason: it burns vast quantities of calories and fat to maintain the infant’s heat balance, keeps its little body warm and protects it from hypothermia.
For a long time, researchers assumed that only babies have brown fat. Then, with the aid of imaging processes, scientists found that adults also have it – and in similar places than newborns. They alos made another startling observation: in overweight people, brown adipocytes have mostly disappeared. Precisely because this tissue also burns a lot of “white” fat, however, it would help overweight people to slim down. After all, following exposure to the cold (or during a diet), brown adipocytes produce a particularly high amount of heat – which causes fat deposits to diminuish. But what regulates and activates the desirable formation of brown adipocytes?
MicroRNA regulates body heating
ETH-Zurich professor Markus Stoffel’s research group, which specialises in microRNA, has now found an answer to these questions. Micro RNA-133, a short piece of ribonucleic acid, is a key regulator for the formation and activation of brown adipocytes during cold exposure. miRNA-133 binds to a messenger RNA that carries the code for the formation of the protein “Prdm16”. Without this transcription factor, neither can precursor cells transform into brown adipocytes nor existing ones become activated: “Prdm16” is the switch that turns up the body heating.
Under the influence of the cold, however, another signal chain is set in motion. Adrenaline is released, which triggers an increase in the formation of “Prdm16” through cellular messenger substances and the breakdown of miRNA-133. Without its opposite number, the protein has a free rein and the body can generate new brown adipocytes and burn a fat stored in white fat cells.
Blocking miRNA encourages cell differentiation
The researchers shed light on the role of miRNA-133 by blocking this RNA sequence with a complementary RNA molecule, an anti-mir, which docks on miRNA-133 and triggers its breakdown in the cell. This intervention promoted the differentiation of precursor cells into brown adipocytes and existing ones were activated – much like after exposure to the cold. If the researchers added extra synthetic miRNA-133 molecules to the cells, however, the opposite happened.
“Potentially, our discovery is medically relevant,” says Professor Stoffel. By stimulating the brown adipocytes, the body consumes more energy and burns fat unceremoniously. Theoretically, at least, this could be an approach to treat overweight people.
Treatment for excess weight?
He can envisage a course of therapy where overweight people are given an anti-mir against miRNA-133 to activate brown adipocytes and kick-start its metabolism. However, the method could have a drawback: miRNA-133 also regulates muscle growth. If it is gone, the muscles could get bigger. Stoffel says that blocking miRNA-133 could thus cause an abnormal enlargement of the heart if it is not applied specifically in brown adipose tissue.
miRNA is already being tested and partly used medicinally. An antimir against Hepatitis C is in phase two of a clinical trial, the ETH-Zurich professor stresses, which just goes to show that miRNA treatments are no longer merely a pipe dream. In order for them to be used as a therapeutic agent, however, anti-mirs need to be altered chemically to render them stable. “Otherwise, the body breaks down these RNA molecules very quickly.” And this would make them unsuitable for therapeutics.
Trajkovski M, Ahmed K, Esau CC, Stoffel M. MyomiR-133 regulates brown fat differentiation through Prdm16. Nature Cell Biology, 2012, Published online 11th November. DOI: 10.1038/ncb2612