Bored at work? Fat chance

Text: Cecilia Odlind, first published in Swedish in Medicinsk Vetenskap, No 4/2019.

Fat cells are annoying, says Kirsty Spalding. The largest cells in the body are difficult to work with.

“They are bulging like balloons, making them prone to break easily. The more overweight a person is, the bigger and bulgier the fat cells are. When they burst, they leak oily fat everywhere. They also float, which means you can’t handle them like you would other cells, and novel methods have to be developed in order to  study them,” says Kirsty Spalding.  

As obesity rates across the world continue to rise, researchers have understood that fat cells not only store and release energy, but that they are also involved in several other bodily processes.

“They affect everything from reproduction to temperature regulation and the immune system. They are also involved in diseases such as cancer. I believe that fat cells assume these roles especially when they become stressed, when they become too big. As such, we are likely to see fat cells featuring a lot in human health as we become increasingly obese,” she says.

The number of fat cells vary

Kirsty Spalding began her research career in neuroscience. Fat cells caught her attention when she worked as a postdoc and realised that it was not known whether adult humans made new fat cells over their lifetime, or not.

“Unanswered questions drew me into the field of fat research.”

What we did know, however, was that when people gain and lose weight, the number of fat cells remains constant, but fat cell size changes. At the same time, it was discovered that progenitor cells isolated from fat tissue could give rise to new fat cells, which indicated that fat tissue had the intrinsic capacity to regenerate itself. Thanks to years of studies, Kirsty Spalding was able to demonstrate that around ten per cent of fat cells are newly formed every year. But we also lose about the same number. And whilst studies show that in some fat depots it is possible to increase the number of fat cells with weight gain, no studies have shown that it is possible to lose fat cells with weight loss.

“The interesting question is therefore why the body keeps making the same amount of fat cells even when the person has lost a lot of weight. What regulates the number of fat cells and what keeps the number stable at a certain level? This is crucial information for us to be able to understand and potentially reduce obesity,” she says.

The number of fat cells do however vary between individuals: On average, obese people have more fat cells than lean people. And the difference can originate early in life.

“Why do some people have more fat cells than others? How much comes down to genetics and how much is environment? At the moment, we don’t know,” says Kirsty Spalding.       

Fat cells like fat

Fat cells like to be a certain size. When fat cells lose fat and become smaller, the signal to the brain telling us to stop eating decreases. The greater the amount of fat cells calling out for fat, the harder it is to resist eating. Researchers believe that this might be an explanation for why people who have been fat or overweight since childhood (which means that they have more fat cells) have a harder time losing weight or staying at the lower weight. This can be interpreted as a fairly disheartening message.

“Yes, this discovery received a great deal of media attention and I received loads of emails from private individuals who were saddened and wondering if there wasn’t anything they could do. But it is not the number of fat cells that impacts your health, but rather their size. So there are still good reasons for keeping your weight down,” says Kirsty Spalding.

The latest study conducted by Kirsty Spalding’s research group, in collaboration with Professor Peter Arner, also garnered a great deal of attention. It provided an explanation for a well-known problem: Reduced lipid metabolism in our adipose tissue makes it easier to gain weight as we get older, even if we do not eat more or move less than previously.

“The change happens gradually throughout our lives,” she says.

Another important question on Kirsty Spalding’s mind is whether all fat cells are the same. It has been known for some time that there is a difference between brown fat and white fat. Brown fat’s primary function is to release energy in the form of heat, rather than storing energy. This type of fat is very common in animals who go into hibernation. Among humans, it was believed that it was most common in newborns. But over the past few years, we have learned that there is quite a lot of brown fat in adults as well. Thin and young people have significantly more brown fat than those who are fat and old.

“It has also been observed that white fat cells can transform into brown ones, becoming what are known as brite or beige cells. This has created expectations among those researching obesity, hoping to one day be able to redirect white energy-storing fat cells into becoming brown energy-burning fat cells.

Kirsty Spalding’s research group has studied this phenomena in human fat cells for some time in their laboratory, and yes, they can be transformed.

“But can all white fat cells be transformed? And most importantly, is it clinically relevant? We still don’t know.”

In order to approach this issue, the researchers have performed single cell sequencing on fat cells, something no one has done until now. The method, developed in part with the assistance of researchers at Karolinska Institutet, analyses the RNA in individual cells to answer the question of which genes are expressed in a specific cell. This, in turn, reveals the cell’s function.

“We see that there seems to be fat cells with different profiles. Whether there are enough differences between them to start categorising them as different types of cells is still being investigated,” she says.

One aspect that Kirsty Spalding enjoys about working with something as unexplored as human adipose tissue is that every result generates new knowledge. This means that the research is not dependent on hypotheses. 

“Everything we do provides answers to unanswered questions, which propels us forward. It really is a luxury to spend your time thirsting for knowledge, getting to ask questions and solve problems,” she says.

Solved criminal cases

Kirsty Spalding’s ability to solve problems has not only helped her in her research, she has also assisted in many criminal cases using a method she developed during her time as a postdoc in Professor Jonas Frisén’s research group around fifteen years ago. For example, she examined the teeth of a four-year-old who went missing in northern Canada in 1965. By conforming that the age of the teeth was consistent with the boy’s age when he disappeared, and by then using other forms of analyses, it was possible to confirm that the cranium they found many years later belonged to the boy.

“He most likely drowned. Whilst a sad story, it was rewarding to be able to close a cold case and return the remais of the child to the family for burial”, she says.

This carbon-dating method, which can be used to determine a cell’s age, utilises the fact that carbon-14 levels increased sharply between 1955 and 1963 due to the world’s superpowers conducting nuclear weapons tests. Since then, carbon-14 levels have been dropping. By measuring the amount of carbon-14 in a population of cells, it is possible to determine the average age of a population of cells.

A few years ago, Kirsty Spalding’s name was once again brought up in crime journalism circles as she was consulted in the case from the Netflix documentary Making a Murderer. The idea was for her analysis method to be used to determine the age of a bloodstain central to the case.

“I was ready to conduct the analysis.”

But the whole affair was put on ice as the defence took a new turn and it turned out that the age of the bloodstain was no longer of significant importance.

Lived alone in a cave

Questions are one of Kirsty Spalding main motivating factors. The interest in figuring things out is a fun and indispensable part of research, she says. 

“But to conduct research also means a lot of hard work and a great deal of uncertainty. Being a researcher is not a profession suited to those who do not love their job,” she says.

When Kirsty Spalding was 19, she lived alone in a remote cave located along the west coast of her native country of Australia for three months.

“I had a surfboard and a guitar, but I had to learn how to build fires, bake bread and catch fish. It was just me and nature. Life was boiled down to its most basic components. When things become difficult, I often mentally return to that place and feel a great sense of calm.”