Our bodies contain two types of fat: white fat and brown fat. While white fat stores calories, brown fat burns energy and could help us lose weight. Now, scientists at the 国际米兰对阵科莫 have found a way of making the white fat 鈥榖rowner鈥 and increasing the efficiency of brown fat.

There have been a lot of studies that have found molecules that promote brown fat development, but simply increasing the amount of brown fat will not work to treat disease

Toni Vidal-Puig

While their study was carried out in mice, they hope that this finding will translate into humans and provide a potential new drug to help fight obesity.

Obesity is a condition in which individuals accumulate more and more fat until their fat stops functioning. This can lead to diseases such as diabetes. However, not all fat tissue is bad: the fat that accumulates in obesity is known as 鈥榳hite fat鈥, but a second form of fat known as 鈥榖rown fat鈥 could be used to treat obesity.

Both brown and white fat are made up of fat cells known as adipocytes, but in brown fat, these cells are rich in mitochondria 鈥 the 鈥榖atteries鈥 that power our bodies 鈥 which give the tissue its brown colour. Brown fat also contains more blood vessels to allow the body to provide it with oxygen and nutrients.

While white fat stories energy, brown fat burns it in a process known as 鈥榯hermogenesis鈥. When fully activated, just 100g of brown fat can burn 3,400 calories a day 鈥 significantly higher than most people鈥檚 daily food intake and more than enough to fight obesity.

We all have some brown fat 鈥 or brown adipose tissue, as it is also known 鈥 in our bodies, but it is found most abundantly in newborns and in hibernating animals (where the heat produced by brown fat enables them to survive even in freezing temperatures). As we age, the amount of brown fat in our bodies decreases.

Just having more brown fat alone is not enough - the tissue also needs to be activated. Currently, the only ways to activate brown fat are to put people in the cold to mimic hibernation, which is both impractical and unpleasant, or to treat them with drugs known as adrenergic agonists, but these can cause heart attacks. It is also necessary to increase the number of blood vessels in the tissue to carry nutrients to the fat cells and the number of nerve cells to allow the brain to 鈥榮witch on鈥 the tissue.

In 2012, a team led by Professor Toni Vidal-Puig from the Wellcome Trust-MRC Institute of Metabolic Science, 国际米兰对阵科莫, identified a molecule known as BMP8b that regulates the activation of brown fat in both the brain and the body鈥檚 tissues. They showed that deleting the gene in mice that produces this protein stopped brown fat from functioning.

Now, in a study published today in the journal Nature Communications, an international team of researchers led by听Drs听Vanessa听Pellegrinelli听and听Vivian Peirce, and听Professor听Vidal-Puig has shown that increasing how much BMP8b mice can produce increases the function of their brown fat. This implies that BMP8b, which is found in the blood, could potentially be used as a drug to increase the amount of brown fat amount in humans as well as making it more active. Further research will be necessary to demonstrate if this is the case.

To carry out their research, the team used mice that had been bred to produce higher levels of the protein in adipose tissue. As anticipated, they found that increasing BMP8b levels changed some of the white fat into brown fat, a process known as beiging and thus increased the amount of energy burnt by the tissue.

They showed that higher levels of BMP8b make the tissue more sensitive to adrenergic signals from nerves 鈥 the same pathway target by adrenergic agonist drugs. This may allow lower doses听of these drugs to be used to activate brown fat in people, hence reducing their risk of heart attack.

Unexpectedly, but importantly, the team also found that the molecule increased the amount of blood vessels and nerves in brown fat.

鈥淭here have been a lot of studies that have found molecules that promote brown fat development, but听simply increasing the amount of brown fat will not work to treat disease 鈥 it has to be able to get enough nutrients and be turned on,鈥 says Professor Vidal-Puig, lead author of the study.

Co-author Dr Sam Virtue, also听from the Institute of Metabolic Science, adds: 鈥淚t鈥檚 like taking a one litre engine out of a car and sticking in a two litre engine in its place. In theory the car can go quicker, but if you only have a tiny fuel pipe to the engine and don鈥檛 connect the accelerator pedal it won鈥檛 do much good. BMP8b increases the engine size, and fits a new fuel line and connects up the accelerator!鈥

The research was funded by the British Heart Foundation, Medical Research Council, European Research Council, WHRI-Academy and Wellcome.

Read more on The Conversation website:

Reference
Pellegrinelli, V et al. Nature Communications; 26 Nov 2018; DOI: 10.1038/s41467-018-07453-x



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