“Obesity cure possible after discovery of fat ‘switch’,” is the somewhat premature headline in The Daily Telegraph.
Researchers have identified a “biological switch” that controls when fat cells convert fat into energy for the body. But the headline fails to make it clear that this discovery was in mice, not humans.
Current thinking is that fat cells start off as “beige”, where they’re essentially in a neutral state. They can then be converted into either white or brown fat cells.
White fat cells store energy and can contribute towards obesity. Brown fat cells are primed to burn energy by warming the body.
It’s possible for white fat cells to be converted into brown fat cells – by fasting, for example – in a process known as browning. In some cases, brown fat cells can switch back to being white fat cells again.
This study looked at this process in mice and found a mechanism that controls this switch. It involved an area of the brain called the hypothalamus and a protein called TCPTP, which acts on insulin receptors.
Researchers found the switch was stuck in obese mice and they were in energy-storing mode all the time, promoting weight gain.
But we don’t yet know if the switch would be the same in humans, and to what extent it contributes to obesity.
Interfering with neural pathways in the brain could have unintended consequences, so any drugs developed to target the process would need thorough testing to make sure they’re safe.
Where did the story come from?
The study was carried out by researchers from Monash University in Australia, and the Department of Neuronal Control of Metabolism in Cologne, University Hospital Cologne, the University of Cologne, and the National Center for Diabetes Research, all in Germany.
The research was funded by the NHMRC of Australia, the Diabetes Australia Research Trust, and the National Imaging Facility.
It was published in the peer-reviewed journal Cell Metabolism.
The UK media coverage of this research was generally accurate, although The Guardian failed to mention anywhere in their article the research was conducted in mice.
Any talk of a cure for obesity being found, as suggested by The Daily Telegraph, is premature.
The study’s results can’t be directly linked to human biology. There’s no way of knowing yet if fat control mechanisms in human brains work in the same way.
What kind of research was this?
This experimental research was carried out in mice to understand the mechanism behind the storage or expenditure of energy in normal and obese mice, as well as during feeding or fasting stages.
This kind of research is very useful for showing how biological mechanisms might potentially work in humans.
But the research is at a very early stage, and there’s a long way to go before therapies or treatments might be available for humans.
What did the research involve?
The researchers looked at brain scans, blood tests and metabolic measurements in mice to examine how the mechanisms in a part of the brain called the hypothalamus work in response to feeding and fasting, and see how these might potentially work in humans.
The hypothalamus is responsible for regulating a number of essential biological processes, including appetite, and regulating body temperature.
The specific area in the hypothalamus the researchers were interested in was the insulin receptor TCPTP.
The researchers looked at the mice’s ability to use energy just after a meal and store energy in between meals by preventing or allowing the action of insulin.
Insulin levels rise after eating as blood glucose levels rise, causing the brain to send signals to start “browning” fat so energy is expended. When insulin levels lower, energy starts to be conserved again.
The researchers looked at beige fat cells and their ability to switch between white fat cell-like states (energy storage) and brown-like states (energy expended).
They also looked at the mechanism that controls these beige fat cells, how this mechanism changes according to eating or fasting patterns (and therefore insulin levels), and whether there are any differences in this mechanism in obese mice.
What were the basic results?
The researchers found beige fat cells’ ability to switch between energy storage versus expenditure was important in a feeding versus fasting context.
They found this was co-ordinated by the hypothalamus and the action of TCPTP on insulin receptors in this area of the brain.
Hypothalamic TCPTP was increased during the fasting phase, which prevented insulin signalling, resulting in less browning of the white fat cells and therefore less energy expenditure.
Hypothalamic TCPTP decreased during the feeding phase, increasing insulin signalling and resulting in more browning of the white fat cells and more energy expended.
The ability to suppress the hypothalamic TCPTP as a result of feeding didn’t work as effectively in obese mice.
Removing hypothalamic TCPTP in obese mice restored browning of the beige fat cells after feeding, increasing energy expenditure once more to promote weight loss.
Mice without hypothalamic TCPTP didn’t become obese when overfed.
How did the researchers interpret the results?
The researchers concluded: “Our studies indicate that the energy expenditure specifically associated with feeding in chow-fed lean mice is reduced in diet-induced obesity.
“The promotion of feeding-induced energy expenditure may provide an approach by which to combat obesity.”
This early-stage research suggests there is potentially a mechanism by which energy expenditure and storage is controlled in normal-weight mice versus obese mice.
Removing a protein called hypothalamic TCPTP, which acts as the “switch” for fat storage, promoted weight loss in obese mice.
This might give us some insight into how weight loss could be promoted in obese humans by turning this switch off.
But at this stage, this is just a hypothesis – we can’t assume the same is true for humans. Many therapies and procedures that appear promising at the outset aren’t always successful in humans.
Given the major disease burden caused by obesity, finding ways to reduce its prevalence is a crucial area of research.