If you melted down the average UK adult, you’d find around 22 kilograms (48.5 pounds) of creamy yellow fat – equivalent to around 88 blocks of lard, enough to fill two-thirds of a small suitcase or cast into 446 dinner candles. Melted, it would easily be enough to paint a large bedroom in a translucent, waxy sheen.
It’s a queasy thought. For centuries, we’ve regarded body fat as an inert, lard-like substance. We carry it everywhere, and frequently despise it – yet this pale, oily tissue is undergoing a radical reassessment. Far from an inert nuisance, it is an organ – one that is alive and surprisingly communicative, has its own memory and is capable of influencing everything from appetite and metabolism to fertility, mood and immunity.
Fat, it turns out, isn’t one thing. It comes in white, brown, beige and even pink forms – each with distinct functions and found in different locations – and contains a mix of immune cells, nerves and blood vessels that contribute to its powers.
“You wouldn’t get pushback today if you claimed fat was an organ, in the same way your lungs or liver or spleen are organs,” says Paul Cohen at The Rockefeller University in New York, who researches metabolic disease and cancer related to obesity. This shift in thinking is reshaping our view of body fat and our understanding of obesity. It challenges how we think about trying to get rid of fat, and is even prompting some scientists to explore how to reprogram it instead – not just to tackle obesity, but to improve our broader health.
Until relatively recently, body fat – also known as adipose tissue – was largely seen as a passive storage depot for excess calories, a layer of insulation against the cold and simple padding. These functions are clearly important: the evolution of body fat may have aided humans in moving out of Africa and surviving in colder climates. Even today, carrying a bit of excess weight reduces the likelihood of older people dying if they fall ill.
“I think the first thing that people fail to appreciate is what a valuable evolutionary step it was to be able to store fuel,” says Randy Seeley, who researches energy balance and metabolism at the University of Michigan. “If you’re not able to do that, you’re a filter feeder: you have to swim in your food.”
But while many organisms possess some form of body fat, in mammals, it has evolved into something much more complex than just a kind of meaty bubble wrap, says Seeley. “It also now becomes integrated into the overall regulation of blood glucose, body temperature and other physiological functions, including bone health.”
Controlling hunger
The first clues that we were underestimating our body fat came in the 1990s with the discovery of leptin. This hormone, secreted by fat cells, acts on the brain to suppress appetite and boost energy expenditure. On the flip side, when people quickly lose fat, leptin levels drop, which the brain interprets as a sign that energy stores might be running low. It responds by ramping up hunger signals and reducing energy expenditure to help you regain that lost fat.
The discovery of leptin cracked open a hidden communications network between fat and the rest of the body. Since then, we have discovered that fat cells release many more hormones and other signalling molecules, some of which communicate with tissues nearby, while some travel much further afield. Together, they are known as adipokines.
What’s more, this communication isn’t only chemical – it’s also electrical. We now have evidence for networks of nerve fibres extending deep inside adipose tissues, forming a direct, two-way line of communication between the brain and our fat.
“The nerve supply in adipose tissue enables a bidirectional and fast communication route with the brain,” says Kristy Townsend, a neuroscientist at The Ohio State University who studies fat. As well as sending messages about energy and metabolism, nerves allow fat to quickly communicate its health status, for instance, whether it is injured or inflamed.
Fat and immune health
Immune cells may also join these conversations, relaying information about inflammation or injury and releasing molecules that help nerves survive and grow. “If you look at the tissue in between all the adipocytes, there’s pretty much every immune cell you can imagine – so fat is also an immune organ,” says Townsend.
In short, fat doesn’t just store energy; it speaks. And together, these adipokines, immune cells and nerve fibres form the vocabulary of an unexpectedly sophisticated organ.
The far-reaching impacts of fat are only now coming to light. Its best-documented role is in energy balance (see “Your unappreciated organ”, below), telling the brain when reserves are full or depleted. But fat’s communication with the brain also seems to extend to our moods. While mood disorders such as depression or anxiety are complex, and stigma or poor body image may also contribute to this, evidence is increasingly linking obesity – particularly metabolically unhealthy obesity – to these conditions.
While the mechanisms are still under investigation, the leading idea is that inflammation within adipose tissue triggers brain inflammation, which in turn alters the balance of neurotransmitters and triggers behavioural changes. Altered levels of leptin may also influence brain reward circuits and mood regulation.
And our fat plays a crucial role in fertility, too. Without a minimum level of body fat, for example, menstruation won’t start or will stop, which makes sense, because entering pregnancy without sufficient energy to sustain a developing fetus could be catastrophic for both mother and child.
“People forget that fat is metabolically really important. Without fat, we have issues with hormonal control, infection [and] immunity,” says Louise Thomas, a professor of metabolic imaging at the University of Westminster in London.
When fat turns bad
So if fat is such a crucial factor in our health, why does it get such a bad rap? The first issue is its location. White fat makes up more than 95 per cent of our total stores and is found both under the skin (subcutaneous fat) and wrapped around internal organs (visceral fat). “Our organs are often sitting in a sea of fat,” says Thomas.
That internal sea can turn toxic. Excess visceral fat is linked to a higher risk of type 2 diabetes, high blood pressure, heart attacks and certain cancers. Growing evidence also suggests it may affect brain function and contribute to conditions such as Alzheimer’s disease.
What triggers this shift from cooperative organ to rogue state is a major focus of research. While white fat cells in both subcutaneous and visceral deposits can expand and contract depending on the body’s storage needs, those surrounding internal organs appear especially vulnerable to the harmful effects of excess fat.
In obesity, these fat cells enlarge and are prone to dying once they reach a critical size. Part of the problem is that their blood supply can’t keep up with their growth. Stressed and suffocating, they release inflammatory molecules as distress signals, attracting immune cells to clear dead or dying cells.
Fat cells, shown in blue, may release distress signals that exacerbate inflammation
Steve Gschmeissner/Science Photo Library
These immune cells intensify the inflammation, with effects reaching far beyond the fat itself. The chemical signals interfere with insulin – the hormone that regulates blood sugar – raising the risk of type 2 diabetes. They are also linked to cognitive changes seen in obesity such as memory and attention problems, and may create conditions that foster tumour growth. Obesity is a risk factor for many kinds of cancer, and often people who are obese tend to have worse outcomes.
Dying or overstuffed fat cells also release fatty acids, or lipids, into their surroundings – and in excess, these can be toxic to surrounding cells. Over time, this lipotoxic stress can damage the network of nerves threaded through fat, a condition known as adipose neuropathy. Obesity, type 2 diabetes and ageing are all linked to this loss of peripheral nerves, which further disrupts metabolism by impairing communication between the brain and fat.
Protecting bone health
Misfiring fat signals can also play havoc with our bones. Most of the time, oestrogen produced by adipose tissue can help protect against excessive bone resorption – where old bone tissue is broken down faster, then new bone can replace it. However, growing evidence suggests that excess fat, particularly visceral fat and fat accumulation within bone marrow, can impair bone quality and increase fracture risk. This is partly because inflammatory cytokines released by adipose tissue can stimulate osteoclasts, the cells responsible for bone resorption, which, in turn, promotes bone loss.
Despite the downsides of dysfunctional fat, adipose itself isn’t the enemy – we need it. And efforts to get rid of it can backfire. Studies of liposuction, a cosmetic procedure that removes targeted fat, suggest that the extracted fat may simply reappear elsewhere. “You may want to remove fat from some locations, but you may like even less where you get it afterwards,” says Seeley, who has been involved in some of this research. “If you remove subcutaneous fat, you’re probably going to end up with more visceral fat in the long run, and that probably leaves you in a worse place than where you were before.”
Not everyone with obesity is unhealthy, either. Between 10 and 30 per cent of people classified as obese based on body mass index seem to escape the usual health effects, such as insulin resistance, high blood pressure and unhealthy cholesterol levels – at least in the short term. This so-called metabolically healthy obesity has intrigued researchers like Matthias Blüher at the University of Leipzig in Germany.
About 15 years ago, Blüher and his colleagues began comparing fat tissue from people with obesity who developed insulin resistance – often a precursor to the development of type 2 diabetes – and those who didn’t. They found that where excess fat sits and how it behaves are both crucial: people with more visceral and liver fat tended to be metabolically less healthy, while those whose adipose tissue contained smaller fat cells, fewer immune cells and a healthier secretion pattern of adipokines appeared to be more protected.
Different types of fat
More recently, the researchers have taken this investigation down to the cellular level, analysing which genes are active in different fat deposits across dozens of people with healthy and unhealthy obesity. Their results, published earlier this year, reinforce that not all visceral fat is equal. “Even within the visceral cavity, it makes a difference where the fat is located,” says Blüher. The highest risk is associated with fat that sits outside of the intestine, although, for now, they aren’t sure why this is the case.
Visceral fat is linked to an increased risk of conditions like type 2 diabetes and high blood pressure
GUSTOIMAGES/Science Photo Library
The fat also looks different in people with healthy obesity: their fat cells are more metabolically flexible – able to switch efficiently between storing and burning energy – pump out fewer inflammatory signals and host fewer immune cells. Their visceral fat also contains mesothelial cells, which can transform into other cell types, perhaps enabling their fat to expand more smoothly without triggering excessive inflammation. Why some people have more of these metabolically healthy cells is probably down to genetics, although lifestyle factors such as diet and exercise may play a role.
Either way, Blüher thinks that these insights could help doctors identify which people with obesity are at the highest risk of complications, and then tailor treatment accordingly.
Reprogramming fat for health
His longer-term dream is to find a way to restore fat’s healthy function – perhaps even transform “unhealthy” obesity into a permanently more benign form. Encouragingly, this may not require dramatic weight loss. Many of the benefits of modern weight-loss drugs and bariatric surgery seem to stem not from the amount of weight lost, but from improving fat distribution and function, says Blüher. “In bariatric surgery, even if people don’t lose a lot of weight, the health benefits start almost immediately.”
Achieving this would be revolutionary, not least because it would prompt a rethink of what a healthy body shape looks like.
And if fat could be reprogrammed to behave more healthily – or the cellular memories of its bloated heyday erased (see “The yo-yo effect”, below) – many more of us might live longer, healthier lives without obsessing over size.
Whether obesity begins in the adipose tissue or the brain is still debated, but it is clear that when communication between the two falters, the whole system drifts off-kilter.
Seeley likens the situation to an orchestra: “All of these organ systems – your liver, pancreas, adipose tissue, muscle and gastrointestinal tract – are all talking to your brain, and your brain is talking to all of them. If your symphony conductor isn’t doing a good job, then even if all your instruments are OK, it won’t sound great.”
In other words, fat isn’t necessarily the problem; it’s an instrument playing slightly out of tune in a misdirected symphony. Many of us have been conditioned to try to shrink, remove or hide our body fat. But the real task is to understand it – to coax this creamy, talkative organ back into harmony with the rest of the orchestra. Because when it plays well, it helps keep the whole body in tune.
Not all fat is created equal. Most of what we carry is white fat, which is predominantly made up of white adipocytes – large, round cells, each containing a single droplet of fat that takes up most of their volume.
White fat is the body’s primary energy store – stashing excess calories away as triglycerides and releasing them as fatty acids for fuel – but it also plays an important signalling role and provides insulation and cushioning, protecting internal organs from mechanical shock.
Tucked around our neck and shoulders and in a few other places are smaller, darker deposits of brown fat, packed with cellular energy factories called mitochondria that burn through fatty acids to generate heat. When activated, brown fat can burn through hundreds of times more heat per gram than any other tissue in the body.
Both kinds of fat may have shaped the course of human history, says Aaron Cypess at the US National Institutes of Health, who studies brown fat. “White adipose tissue is one of the main contributors to the establishment of civilisation, because if you don’t have to spend all your time eating, you’re freed up to do something else,” says Cypess. “Brown fat helped in a different way, because it allows us to stay warm. We can therefore adapt to many different environments.”
Fat comes in other hues, too. Beige fat cells, sprinkled through white fat, can adopt brown-like characteristics following exercise or prolonged exposure to cold, shifting from quiet storehouses into tiny furnaces that burn energy instead. During pregnancy and lactation, meanwhile, white fat cells in the breasts transform into pink fat, supporting milk production.
Saverio Cinti at Marche Polytechnic University in Ancona, Italy, who has dissected the entire “adipose organ”, all the interconnected lobes and pads of fat, in mice and humans, argues that this rainbow-hued network of lobes and pads – which connect at the base of the neck and pelvis – forms a single, integrated system.
“The old concept of adipose tissue as a connective tissue is absolutely obsolete,” he says. “No one questions that the stomach is an organ: it’s a well-defined, anatomically dissectible structure, made of different tissues cooperating for digestion.”
The adipose organ is similar, he says: “It is a unified structure, composed of two tissue types – white and brown adipose – that cooperate to manage the body’s energy, balancing storage and heat production according to the organism’s needs.”
Losing weight is hard – but keeping it off is even harder. Even with blockbuster GLP-1 drugs like Wegovy, Ozempic and Mounjaro, the pounds often creep back on once treatment stops, hinting that fat may have a stubborn memory of its own.
This makes evolutionary sense. “In an environment where there’s not enough food, it probably helps the body to remain hungry if you lose fat,” says Ferdinand von Meyenn, at ETH Zurich in Switzerland.
Until very recently, obesity and the health complications that often accompany it were rare, so there hasn’t been strong evolutionary pressure to develop a counter-strategy to protect against the negative consequences of excessive food availability.
Von Meyenn and his colleagues have been investigating the molecular basis for the problematic “yo-yo” effect often seen with dieting. They suspect that chemical, or “epigenetic”, markers on the genes of fat cells may hold the key.
Some of these insights came from studying fat samples taken from people undergoing bariatric surgery for weight loss. When they compared these samples with those from lean individuals, they found differences in the activity of various genes, which persisted even after people lost substantial amounts of weight.
Further experiments on mice that gained and then shed weight revealed a similar pattern. Next, von Meyenn and his colleagues looked at their epigenomes – the chemical markers that sit on genes and influence how they are switched on or off. Here, too, they found that obesity left a distinct and lasting influence.
Mice with these epigenetic patterns also gained weight more quickly when re-exposed to a high-fat diet, and when their fat cells were grown outside the body, they appeared primed to store more fat and glucose in their fat cells.
Von Meyenn warns that these epigenetic changes haven’t definitively been proven to cause the yo-yo effect. Even if they do, it is possible that other organs, including the brain, might similarly store memories of obesity.
It is also unclear how long fat cells might retain such memories.
Experiments so far suggest that these epigenetic changes last for up to six months, but nobody has looked beyond this yet. “We also see that the longer animals remain obese, the more pronounced the effects on the epigenome are,” says von Meyenn.
If epigenetic memory is part of the problem, he thinks that finding a way to erase these marks might eventually help prevent weight regain: “It probably wouldn’t prevent people from becoming obese again if they really wanted to, but it might take away the urge to overeat that many people experience.”
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