Hopes for chemicals that turn 'bad' fat 'good'

Behind the Headlines

Tuesday December 9 2014

A safe and effective weight loss pill is likely to prove extremely popular

There is currently no drug that can replicate exercise's benefits

"Scientists discovered how to trigger a molecule which can turn 'bad' white fat cells into 'good' energy-burning brown fat cells," The Daily Telegraph reports, saying that it could "replace the treadmill". But this proof of concept lab research didn't involve any humans.

White fat is what most people think of when they are talking about fat – it stores energy, adds bulk to the body, and too much can lead to obesity.

Brown fat helps to keep body temperature stable by burning energy, and this uses up calories. Brown fat is mostly found in newborns, but researchers think if they could convert white fat cells into brown fat cells in adults, this could lead to weight loss.

In this study, researchers have identified a number of potentially promising chemicals that could be used to create a drug that can turn white fat into brown fat.

A pill that allows us to eat what we want and not gain weight might become a reality at some point in the future, but this is unlikely to be an option in the short term.

Researchers have only done tests on cells in the lab so far. They do not yet know whether the chemicals will be effective and safe in humans.

Even if an obesity-busting pill becomes a reality, it is unlikely to replace all of the benefits of keeping active and eating a healthy balanced diet – so do still ask Father Christmas for that treadmill.


Where did the story come from?

The study was carried out by researchers from the drug company Roche, Harvard University and Massachusetts General Hospital in the US.

The research was funded by F. Hoffmann-La Roche, the US Institutes of Health and Harvard University, and was published in the peer-reviewed journal, Nature Cell Biology.

Both The Daily Telegraph's and the Mail Online's reporting of the study was broadly accurate. But claims made in the headlines that the pill could replace exercise, which is reported in a quote from one researcher, are probably overly optimistic.

Even if a drug was successful in leading to weight loss without the need for exercise, exercise brings additional health benefits.

These include enhanced cardiovascular health and a reduction in the risk of some cancers, bone fractures and dementia, as well as an improvement in symptoms of mild depression.

To be fair to the Mail Online, their article does say the research team pointed this out, but not until the end of the story.


What kind of research was this?

This was laboratory research looking for chemicals that can convert fat-storing cells (white fat cells) into energy-burning cells (brown fat cells).

Mammals have two types of fat – white and brown fat. White fat stores excess energy and helps regulate feelings of fullness. Brown fat keeps body temperature stable by burning fat to produce heat.

In humans, brown fat cells are mostly found in newborn infants to help keep them warm before they are able to shiver.

As we grow, most brown fat cells are replaced by white as we have less need for them, but studies have found the more brown fat we have the less likely we are to be overweight.

Animal studies have suggested white fat cells can be prompted to change into brown fat cells by exposing them to certain conditions (such as cold) or certain molecules.

The researchers say if they could find a way to convert white fat cells to brown fat cells in humans, it could be a promising way to combat obesity.

In particular, the researchers wanted to develop a way to rapidly assess a wide range of chemicals for this fat cell-converting ability, and test any chemicals they identified as showing potential.

This is a common way to start looking for chemicals that could be developed into useful drugs. It is a very early stage of drug development, and many of the chemicals identified will never make it to the pharmacy shelf.

And those that do can take a long time to get there. If the process of creating a successful drug was similar to an X-Factor-style reality talent show, the work being done in this study would be akin to the first round of public auditions.


What did the research involve?

The researchers started with human stem cells in the lab and treated the cells with chemicals that induce them to develop into white fat cells.

Brown fat cells produce a special protein called UCP1, which white fat cells do not. The researchers used this protein as a "marker" for identifying cells that had started to behave like brown fat cells.

They tested 867 different chemicals to see if they could cause the cells to "switch" to being like brown fat cells. They also looked at whether these chemicals caused the cells to look more like brown fat cells under the microscope.

White fat cells have one or a few large drops of fat inside them, while brown fat cells contain many small droplets of fat. Brown fat cells also possess more of the energy-producing "powerhouses" of the cells called mitochondria.

The researchers also looked at whether the switched cells were producing more mitochondria and were more metabolically active, and what happened if the chemicals were removed from the cells.

They tested whether the chemicals identified could cause cells collected directly from human fatty tissue and white fat tissue from mice to turn into brown fat cells.

They also looked at whether the genes that were active in the switched cells were more like white fat cells or brown fat cells.

The researchers also carried out other experiments to look at how the chemicals they identified had their effect. This could also help them to identify other ways to get white fat cells to switch.


What were the basic results?

The researchers identified 83 chemicals that caused white fat cells to become brown fat cells, producing the brown cell-specific protein UCP1 in the laboratory. These switched cells also looked like brown fat cells under the microscope.

Three of these chemicals showed the greatest ability to get white fat cells to switch to UCP1-producing brown fat cells.

The switched cells were also producing more mitochondria and were more metabolically active, burning more fats to make heat.

Two of these chemicals inhibited proteins called JAK and SYK. One was a drug called tofacitinib, which is currently used to treat rheumatoid arthritis.

Even after these inhibitors were removed from the switched cells, they were still behaving like brown fat cells 28 days later.

The researchers carried out further tests on these compounds and found they could cause cells collected directly from human fatty tissue to turn into brown fat cells.

They could also cause white fat cells from under the skin of mice to convert into brown fat cells in the lab, but not fat cells from the abdomen.

Finally, they found although the switched cells were acting more like brown cells, they still had patterns of gene activity that were more like white fat cells. This suggested the cells had not entirely converted to brown fat cells.


How did the researchers interpret the results?

The researchers concluded they have developed a way to identify chemicals that can get fat-storing white fat cells to switch to behaving like energy-burning brown fat cells.

Using this system, they identified two inhibitors of the JAK protein, which can cause white fat cells to take on brown fat cell-like characteristics and metabolism in the lab.

They say a role for the JAK pathway in controlling fat cells was not previously known about, and this knowledge could help identify chemicals that could be used to treat obesity.



This laboratory research has identified chemicals that can make fat-storing white fat cells behave more like energy-burning brown fat cells in the lab.

They hope these or other chemicals identified using their new method could eventually help combat obesity.

A pill that allows us to eat what we want and not gain weight is a holy grail for many. While it might become a reality at some point in the future, this is unlikely to happen any time soon.

As the authors themselves note, they have only done tests on cells in the lab so far. They do not yet know whether the chemicals will have the same effect within the body or, more importantly, whether they would be safe to use.

The researchers are right in sounding a note of caution. The chemicals they have identified as working best so far inhibit a protein called JAK, which plays an important role in the immune system.

This could make using JAK inhibitors to treat obesity more difficult, as it could mean side effects for the immune system.

This research is at a very early stage, and the pill will certainly not be in the stores in time for Christmas, so you are still going have to hit the gym if you want to get rid of any excess calories you consume over the festive period.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

Obesity pill to 'replace treadmill' being developed by Harvard University. The Daily Telegraph, December 8 2014

The obesity pill that could replace exercise by turning 'bad' fat to 'good'. Mail Online, December 8 2014

Links to the science

Moisan A, Lee Y, Zhang JD, et al. White-to-brown metabolic conversion of human adipocytes by JAK inhibition. Nature Cell Biology. Published online December 8 2014


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