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The popular new types of weight-loss drugs not only result in loss of body fat, but also muscle. But now a team of researchers are developing a drug that spares the muscles by targeting fat-cell burn. 

Excess fat around the waist, on the thighs and buttocks and around internal organs is what people affected by clinical obesity are trying to shed. In many cases, the drugs taken for obesity cause people not only to lose fat but also muscle. 

This is why a team of researchers who call themselves Incipiam, in collaboration with researchers from Rigshospitalet and the University of Copenhagen, Denmark’s largest hospital, and funded by the Lundbeck Foundation, have set about developing a new type of medicine that spares more muscle.

As project lead on the Incipiam team, Tora Henriksen, cell biologist and postdoctoral researcher at Rigshospitalet, is heading up this drug development project.

“The new types of weight-loss drugs are primarily directed towards appetite regulation in the brain. Instead, we want to target the fat cells and boost fat metabolism at cellular level,” she explains.

Targeting a fat cell receptor

The key to weight loss without massive muscle loss is a specific receptor on fat cells. A receptor is a molecule on or inside the cell that is triggered by signalling substances to initiate various intracellular processes. 

In this case, the receptor controls energy conversion within the cell. 

“We want to identify a substance that increases the rate of fat metabolism by binding to this receptor in the fat cells,” Henriksen explains. 

The receptor is present on all fat cells; both the ‘ordinary’ white ones, but also the brown fat cells we have fewer of. 

For some years, brown fat has received a lot of attention from researchers, and it was the resulting studies of this fat that identified and investigated this particular receptor. 

The special characteristic of brown fat is that it is activated by cold, ensuring that extra energy is burned to heat up the cells. 

Brown fat is common in hibernating animals and in newborns, and for many years was not believed to exist in the body of adult humans. The discovery that everyone actually does have brown fat kick-started Henriksen’s interest in fat cells.

“We can see a correlation with healthiness in people who have a lot of brown fat. It appears that brown fat protects against metabolic disorders, cardiovascular disease and type 2 diabetes. And that’s the protective effect we are also hoping to achieve,” she explains. 

Some scientists are researching gene regulation with the aim of reprogramming white fat cells to burn fat more like brown fat cells. 

In this particular project, however, the researchers are taking a different approach by targeting fat cell energy conversion.

“People affected by obesity have so many white fat cells that if we can get those cells to burn more fat, we’ll be giving their weight loss a real boost,” says Henriksen. 

Testing cells in a ‘fat bank’

The team has already homed in on specific chemical substances to be tested by an external laboratory specialised in developing the medicinal ingredients, and the lab will also be identifying several candidates for the research team to test on live mice as well as on cultured fat cells from humans and mice. 

Some of the experiments will be conducted in collaboration with the Centre for Physical Activity Research at Rigshospitalet, which has a ‘fat bank’ of adipose tissue samples supplied by surgeons from operations on more than a hundred patients. Experiments on mice and mouse tissue will be performed in collaboration with the University of Copenhagen. 

As a potential Frontier Grant-holder, Henriksen received feedback from the Lundbeck Foundation’s experts during the assessment process.

“It's been amazing. Usually, you write your application and cross your fingers. But on this programme, we get feedback along the way, which is invaluable. It’s been a really great process. I was given other angles and suggestions for doing things, which seemed obvious afterwards, but which I would never have come up with myself.”

The aim is for the project to result in a weight-loss pill. Initially, it will be aimed at people affected by obesity and diabetes because in some cases they benefit less from the new types of weight loss medication than people affected by obesity alone. 

And there is a need for many different types of weight loss therapies, believes Henriksen, who explains that:

“Obesity is caused by various factors, which is why a larger palette of treatment options are needed.”

If they make it all the way to the pharmacy shelves with a new ‘slimming pill’, demand will be virtually guaranteed.

A forecast from the Danish Institute of Public Health in February 2024 predicts that demand for drugs to treat obesity is already on a steep rise. The prediction is that the proportion of adults in Denmark with obesity is set to increase from one in five in 2021 to around one in three by 2040.

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