Researchers have found the genetic switch off of brown fat, without which they hope to stimulate combustion

Brown fat. Mice, rats and babies need it to stay warm. And Maastricht’s research already showed that adults also have brown fat. Brown fat, which is located in the neck between the shoulder blades in humans, has the special property that it can convert calories into heat, unlike white body fat, which mainly functions as storage. The big question: can you stimulate combustion? And one step further: can you use brown fat against obesity?

Much research focuses on activating this special fat. What causes the thermostat to turn on when you get cold? But a Danish-German research group has now found, more or less by chance, the switch-off switch for brown fat: a gene that generates the protein that stops energy combustion in brown fat. They’re publishing about it this week Nature Metabolism.

The trail ran via a gene with a protein that was already known, AC3. The group investigated the effect of AC3 and accidentally found a shortened variant: AC3-AT. “And what was surprising: it does not stimulate combustion, but actually turns it off,” says Jan-Wilhelm Kornfeld, who, as a professor at the Southern Danish University, studies how genes influence the functioning of fat cells with funds from pharmaceutical company Novo Nordisk. “What you then want to know is whether you can eliminate that off switch, in order to keep the brown fat active.”

professorJan-Wilhelm Kornfeld There are probably more buttons like this

In mice where the gene was disabled, the researchers saw that the brown fat became hyperactive. These mice gained less weight and had healthier blood sugar balance than mice with the AC3-AT gene, where the off button still functioned.

Although you probably can’t speak of ‘the’ off button. “We found a long list of new genes, which we want to investigate one by one,” says Kornfeld. “We know what they look like, but not what they do. There are probably more buttons like this.”

The researchers do not know whether human brown fat becomes just as active when you disconnect the off button. Although humans have a similar gene, it is unclear how many people have this protective fat and to what extent it contributes to metabolism. According to Kornfeld, 5 to 10 percent of adults have brown fat and burn 200 to 400 calories per day.

Complex control system

Brown fat appeals to the imagination in a world where many people consume more calories than they burn. Kornfeld: “The pharmaceutical industry is now mainly looking at ways to limit food intake. The knob we can still turn is that of outgoing energy. The activity of brown fat is more similar to that of muscle than white fat. Why do those cells look alike, and can you convert white into brown fat? We want to understand that better.”

If Kornfeld wants to convey something, it is how complicated genes work. “Biological systems have their own way of regulating themselves. Apparently there are limitations built in, because being constantly on is disadvantageous.” He emphasizes: this is all still fundamental research, there are no medicines that do something with brown fat yet.

This study is a step in better understanding the complex regulatory system of brown fat, says emeritus professor Wouter van Marken Lichtenbelt, the discoverer of active brown fat in adults. “The simple story is: when you come into the cold, your sympathetic nervous system switches on, which has extensions in the brown fat cells and which responds by generating heat. More complicated is that regulatory proteins determine how this happens. This study shows that there is also a ‘back loop’, a retroactive mechanism. Ultimately, you naturally want to know how you can apply this and develop medicines that intervene in this.”

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Van Marken Lichtenbelt wrote a book about body temperature with an entire chapter about brown fat. He does not see it happening that obesity can be tackled through brown fat. “But active brown fat can have beneficial health effects. The mice without an off switch in this study also showed that they had better blood values.”

The control system may be complex, but anyone can put brown fat to work, says Van Marken Lichtenbelt. “Going into the cold, looking for more variation in temperature – that makes your body active.” Kornfeld sees many people swimming in the winter in Scandinavian countries. He doesn’t know whether they swim because they can withstand the cold or the other way around. “But there are studies that show that winter swimmers have a higher temperature in the neck.” The stove burns where the brown fat is.

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