Growing Fat To Get Slim
While normal white fat stubbornly stores excess calories on hips, bellies and thighs, over the last few years a picture has emerged of a different kind of fat – one which, paradoxically, might help us to lose weight. This is brown fat, which challenges all our assumptions about the fat in our bodies: it burns calories rather than storing them.
It was only six years ago we discovered that brown fat exists and is active in adults. Since then, it has become the focus of attention as a potential tool to help combat obesity and its related diseases. And the idea that there might be a way to burn through calories without the need to exercise is a tempting prospect for many of us.
“We all know you only need a modest change in energy balance to put on weight – eating one or two extra biscuits a day is enough,” says Michael Symonds at the University of Nottingham, UK. “So if you could activate brown fat, or increase its activity, you could potentially reduce your body weight.”
Symonds is one of a number of researchers working to develop behavioural, surgical and pharmaceutical therapies that might harness the power of brown fat, and some of these could be as simple as taking a cold dip in the pool or eating spicy food.
What makes brown fat so interesting is its ability to burn food directly to produce heat, whereas energy extracted from food is usually stored first, then released during activity such as exercise. It can produce 300 times more heat per gram than any other tissue in the body. This is because brown fat cells have a disproportionately high number of mitochondria – the small energy producing structures in cells – which also gives the stuff its eponymous colour. These mitochondria are slightly different from those in other cells, too, because they contain a protein called thermogenin, or UCP1, which enables brown fat to turn energy to heat directly.
This furnace-like ability is vital for regulating temperature in some mammals and in babies, who are unable to shiver to keep warm. But until recently it was thought to become defunct after infancy in humans. Then in 2009, several studies showed that brown fat was present and functional in adults in the neck, shoulders and around the spinal cord.
This discovery changed the question from whether adults have brown fat, to whether we can make use of it to help with weight control. “It was a eureka moment,” says Symonds.
The amount of brown fat each of us has varies, though. Slimmer people tend to have more of it, which might help explain why some people seem to burn through everything they eat, while others pile on the pounds.
So the first step is to find out how much, if any, of this “good” fat you have. Because brown fat is activated when the body is exposed to the cold, Symonds and his team have helped pioneer the use of a thermal imaging camera to detect it.
When animals are cold, they initially regulate their temperature by shivering. But after repeated exposure, shivering decreases while energy expenditure stays the same. Studies in rodents have shown that this is down to brown fat activity. If the same is true in humans, then regular cold exposure could help you adapt to the cold and burn calories in the process.
Evidence for this comes from an intriguing study conducted by the US army in the 1960s, which subjected 10 almost nude men to temperatures of 11 °C , for 8 hours a day for a month. Electrodes on their skin showed that, like rats, shivering decreased after about two weeks, suggesting that their bodies had somehow adapted to the cold. The team concluded that another metabolic process was at work, although it remained a mystery.
Fifty years later, Anouk van der Lans at Maastricht University in the Netherlands and colleagues wondered whether brown fat was responsible. So in 2012 they recreated the study using PET scans and fat and muscle biopsies to measure brown fat activity, as well as monitoring shivering. After 10 days, brown fat activity had increased and the subjects were better at producing heat without shivering, so they shivered less. They also found the cold easier to tolerate.
Encouragingly, in this study, a temperature of about 16 °C was cold enough to switch on the tissue. “Nobody thinks that getting so cold that you’re uncomfortable is necessary,” says Aaron Cypess of the US National Institute of Diabetes and Digestive and Kidney Diseases, an author of one of the 2009 papers.
How many calories can you expect to shed? Estimates vary hugely. One trial of Japanese men found that spending 2 hours a day in a
17 °C room for six weeks boosted brown fat activity by 50 per cent, and got rid of 5 per cent of their body fat. At the start of the experiment the men burned 108 calories during 2 hours in the cold, but this rose to 289 calories after doing it every day for six weeks.
That doesn’t necessarily mean all those calories are burned by the brown fat itself – in studies that only involve short bursts of cold exposure, it could be down to other mechanisms like shivering. For example, one study of volunteers with an average of 50 grams of brown fat found they burned around 300 extra calories a day when exposed to moderate cold for 30 minutes – but brown fat only accounted for 20 calories of this.
Despite the mixed results, those figures are encouraging enough for some people to make cold exposure part of their daily routine. “The mechanism of how it happens is important to understand, but for practical reasons, the result is what people care about,” says Wayne Hayes, a NASA scientist who has created the Cold Shoulder, a waistcoat filled with ice packs designed to activate brown fat.
Cypess and others believe that brown fat could make a contribution to weight loss strategies with regular cold exposure. But what if you don’t like the cold? There could be a tastier alternative.
BEIGE IS THE NEW WHITE
Capsaicin, a compound in chillies, seems to stimulate brown fat in a similar way. Mice fed capsaicin as part of a high-fat diet, for example, have increased metabolic activity and don’t put on weight. This fits with a small study in which 10 men who took capsaicin pills daily had greater brown fat activity in the cold and burned more calories after six weeks.
“Capsaicin is promising as it is natural, and relatively safe and inexpensive,” says Cypess. “But we are awaiting the definitive experiment showing that a dose of capsaicin directly leads to activation of brown fat.”
In the meantime, brown fat could have other benefits aside from calorie burning. It releases hormones that help regulate the metabolism of glucose and fatty acids, so might be useful to help treat diabetes and fatty liver disease. Humans and other animals with high brown fat levels have been shown to have better blood sugar and insulin regulation.
But there is a hitch: we have paltry amounts of brown fat and obese people have especially low levels. Stores also deplete as we age.
For that reason, arguably the biggest recent breakthrough in the field has been the identification of a third kind of fat, called beige fat. First described by Bruce Spiegelman at Harvard Medical School in 2012, beige fat has a different origin to classical brown fat, but it contains the same all-important protein, UCP1, which burns calories to generate heat. And while brown fat forms in tight pockets, beige fat is dispersed in white fat cells. Even better, it might be possible to transform white fat into the calorie-burning beige variety (see “Flavours of fat”).
“With most experiments on brown fat you don’t induce much new tissue, you just activate it,” says Ronald Kahn at the Joslin Diabetes Center in Boston. “With beige fat you get both an increase in the activity, and in the amount. So this is where people believe there are big therapeutic opportunities.”
While most research has so far been in rodents, there is tentative evidence that humans too can turn white fat to beige. One way could be to throw off the duvet. Men who slept in 19 °C bedrooms with only bed sheets had 42 per cent more brown fat after four weeks, found Francesco Celi at Virginia Commonwealth University and colleagues. Glucose uptake increased in white fat, suggesting a rise in beige fat cells nestled within it. The men’s insulin resistance, which is a key issue in diabetes, also improved.
Exercise might also help convert cells. Celi has found hints that a hormone called irisin, produced when muscles contract, stimulates white fat to produce beige fat cells, although the findings are still being debated.
THIRD PILLAR OF WEIGHT LOSS
This highlights a big problem with thinking that boosting brown fat with cold exposure is an easy option: to some people, feeling cold is about as unappealing as slogging it out in the gym or living off salad. And our natural response to cold is often to eat more.
So a better tactic might be to find easier ways to simulate these effects. One hope is mirabegron, a drug developed as a treatment for an overactive bladder that also stimulates receptors on the surface of brown fat cells. In January, a team led by Cypess found an increase in brown fat activity in 12 volunteers after they were given a dose of mirabegron. Their resting metabolic rate increased by 203 calories a day. And it works on brown and white fat. “Mirabegron causes white fat stores to break down, likely to be consumed as fuel by brown fat and other organs,” says Cypess.
Another approach might be to convert white fat to brown in the lab and then reinsert it into the body. In 2010, Yu-Hua Tseng at Harvard’s Joslin Diabetes Center took fat precursor cells from muscle and white fat tissue in mice and exposed them to proteins that influence development into brown fat cells. When they then injected them back into the mice, the treated cells developed into brown fat. Tseng’s team has now identified the same mechanism in human fat cells.
A drug that mimics the effects of cold may not be far away either. A team at the University of California has discovered that in cold conditions the body sends signals to immune molecules called macrophages, which trigger browning of white fat to generate heat. Injecting mice with a dose
of these signalling molecules activated the same immune response without the need to get cold, and the mice started burning 10 per cent more energy.
Combining such approaches with cold exposure could increase brown fat’s impact. It’s likely that brown fat will become the third pillar of weight loss advice, says Cypess. “When you go to your physician, they’ll advise you on eating right, exercising and keeping your brown fat healthy,” he says. “And my hope is that if a person is uninterested in cold exposure they will be able to take a drug.”
Until then, brown fat might not be the magic bullet so many hope. But it could be extremely effective for weight loss if used in combination with reducing calorie intake, says Kahn. Even a conservative estimate of burning an extra 100 calories a day would equate to losing around half a kilogram a month.
And with developments in thermal technology to monitor brown fat, Symonds is optimistic that screening for it could become routine. “It could provide an index of your metabolic health and tell you whether you are at risk of weight gain,” he says.
Source: New Scientist (by Chloe Lambert)
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