Antitumor drug turns white fat into brown

Researchers at the Gladstone Institute, working under the leadership of Dr. Sheng Ding, have found that the anti-tumor drug bexarotene, approved by the US Food and Drug Administration (FDA), turns white fat into brown.

Brown fat differs from the more common white fat, whose main function is to store energy. Brown fat, on the contrary, helps the body burn energy with the release of heat. Newborns usually have a small amount of brown fat, but as they get older, it almost completely disappears. For adults whose body retains brown fat, a smaller body weight is characteristic, and an increase in the amount of brown fat in the body by only 50 g can provide a reduction in body weight by 5-10 kg per year.

As part of their study, the authors used a cellular reprogramming method to transform muscle progenitor cells and white fat cells into brown fat cells.

In search of a drug that ensures the conversion of cells in the right direction, they tested 20,000 chemical compounds. The most promising candidate turned out to be the antitumor drug bexarotene (Bex), which was quite unexpected, since the participation of the target protein of this drug in the formation of brown fat was not previously known.

Bexarotene selectively activates a key regulatory protein known as the retinoid X receptor (RXR) and regulates the functioning of a complex of other cellular proteins. Activation of RXR triggers a cascade of changes in muscle progenitor cells and white fat cells, eventually leading to their transformation into cells similar to brown fat cells. In particular, the activation of RXR under the action of bexarotene activates genes necessary for the formation of brown fat and suppresses the activity of genes associated with white fat and muscle cells.

To test the ability of bexarotene to change body weight, the researchers kept mice on a high-calorie diet for 4 weeks, with half of the animals receiving bexarotene. As a result, the mice receiving the drug had more brown and less white fat in their bodies, while they burned more energy and gained less weight than the control group animals.

The researchers believe that their proposed approach can be used to combat obesity and type 2 diabetes. However, bexarotene is not very specific and can cause adverse side effects, so the next stage of work will be the creation of a safer drug with a more targeted effect, selectively influencing the activity of genes involved in the formation of brown fat.

Article by Baoming Nie et al. Brown Adipogenic Reprogramming Induced by a Small Molecule is published in the journal Cell Reports.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on Gladstone Institutes: Scientists Discover Drug that Increases "Good" Fat Mass and Function.

23.01.2017