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Babies' brown fat diminishes quickly in infancy.

Brown fat can help you lose weight, as it burns calories to produce heat

Brown fat, once thought to exist only in babies, might offer a solution to the obesity epidemic

Fat that makes you thin? That sounds like a contradiction, but it has become a hot topic among researchers racing to find a safe and effective solution to obesity and its associated metabolic diseases.

The spotlight is on brown fat, a type of "good fat" which until a few years ago was thought to exist only in babies and small animals. Found mainly in the neck, around the collarbone and upper half of the spine, brown fat is nature's way of helping infants keep warm while they haven't yet developed the ability to shiver to maintain their body temperature.

Unlike white fat - which infamously shows up as flabby bellies, love handles and plump thighs - brown fat burns, rather than stores, calories (in the process producing heat).

About 10 per cent of a newborn's total body fat is brown fat, but this quickly diminishes in infancy, according to Roger Wong Hoi-fung, an assistant professor at the University of Hong Kong's department of chemistry.

Dr Roger Wong Hoi-fung, assistant professor

In 2009, researchers at the Joslin Diabetes Centre in Boston, the US, showed for the first time that brown fat existed in adults - although in different amounts based on a variety of factors such as age, glucose levels and level of obesity.

Now, researchers, including Wong, are hoping to unlock the secrets behind brown fat. They're searching for ways to preserve, make more of, or activate brown fat, ultimately, to develop a tool to combat the epidemics of obesity and type 2 diabetes, fatty liver and other metabolic diseases.

A study co-developed by Wong and published last month in the journal is among the latest in a slew of brown fat research studies in recent years.

Wong, working with former colleagues at the University of California, Berkeley, discovered a new protein that is critical for the formation of brown fat, and which level increases during exposure to cold temperatures.

In tests on mice, extended exposure to chilly air (four degrees Celsius) also triggered the protein, called transcription factor Zfp516, to help white fat become more similar to brown fat in its ability to burn energy.

Brown fat cells and white fat cells under the microscope.

The researchers found that mice with boosted levels of the Zfp516 protein gained 30 per cent less weight than control mice when both groups were fed a high-fat diet for four weeks.

"If you can somehow increase levels of this protein through drugs, you could have more brown fat, and could possibly lose more weight even if eating the same amount of food," says principal investigator Hei Sook Sul, UC Berkeley professor of nutritional science and toxicology.

In another recent study that appeared in in November, a team of Chinese researchers led by Dr Guang Ning of the Shanghai Institute of Endocrine and Metabolic Disease found that the naturally occurring plant alkaloid berberine increased energy expenditures in mice by increasing brown fat activity.

Genetically obese mice injected daily with berberine - used in traditional Chinese medicine herbal concoctions to treat diarrhoea - for four weeks showed limited weight gain, improved cold tolerance and enhanced brown fat activity.

Based on this study, Wong hypothesises that berberine could activate the Zfp516 protein to "brown" white fat and is now working with his Hong Kong University colleagues to prove this. The drug, mirabegron - approved by the US Food and Drug Administration to treat overactive bladders - may boost brown fat's metabolic powers.

In a study funded by the US National Institutes of Health and published last month in , all 12 young, healthy male participants showed higher brown fat metabolic activity with a daily dose of 200 milligrams of the drug.

At its peak level in the blood, the drug increased the men's resting metabolic rate by 203 calories per day. While the dose was higher than the 50mg dose approved for overactive bladder, the treatment was well tolerated.

You could lose more weight even if eating the same amount of food
Hei Sook Sui, University of California, Berkeley

Brown fat is distinct from white fat because it contains energy-burning organelles called mitochondria, which contain iron and give brown fat its hue. Even in small amounts, brown fat can burn a large amount of calories.

Wong says although less than 5 per cent of fat in our bodies is brown fat, it burns up to 20 per cent of basal metabolic rate calories, which makes up about 70 per cent of total calorie expenditure in a day (the rest being from physical activity). White fat burns "almost negligible" calories, he says.

Younger people, as well as thin adults with normal blood glucose levels, were also more likely to have larger amounts of brown fat, according to the 2009 Joslin study.

Individuals over the age of 64 and with high BMI scores were six times less likely to have substantial amounts of brown fat, says Joslin's chief academic officer Ronald Kahn. In addition, women had detectable brown fat twice as often as men.

Hydrastis canadensis

But in general, adults have little brown fat because we lose it when we don't use it, says Wong. Sul notes that outdoor workers in northern Finland who are exposed to cold temperature have been found to have a significant amount of brown fat compared with indoor workers of the same age.

A study by endocrinologist Dr Paul Lee from Sydney's Garvan Institute of Medical Research, published last June in the journal , shows the plasticity of brown fat in humans.

For four months, five healthy men spent at least 10 hours each night in a temperature-regulated room at the US National Institutes of Health Clinical Centre in Washington. They lived normal lives in the day.

Each month, the temperature changed from 24 degrees, to 19, to 24, and finally to 27 degrees. It was found that during the 19 degree month, brown fat increased by about 30 to 40 per cent. At 24 degrees, brown fat levels returned to baseline. In the warm final month, the volume of brown fat fell to below the baseline.

Apart from cold exposure - which can be unbearable after a while - exercise is equally capable of stimulating the "browning" of white fat, found an earlier study by Lee.

He found that during both cold exposure and exercise, levels of the hormone irisin (produced by muscle) and FGF21 (produced by brown fat) rose. Specifically, an hour of moderate exercise resulted in rises in irisin equivalent to 10 to 15 minutes of shivering in the cold. In the lab, irisin and FGF21 turn human white fat cells into brown fat cells over six days.

Among the metabolic benefits of increased brown fat was heightened insulin sensitivity - suggesting that people with more brown fat require less insulin after a meal to bring their blood sugar levels down. Lee sees promise in brown fat for people with diabetes, whose bodies have to work hard to bring sugar levels down after a meal.

The alkaloid berberine, found in Coptis japonica could be the key to converting brown fat to white.

One challenge facing researchers trying to harness the powers of brown fat is finding a better way to detect and measure brown fat activity in humans. Radiation-based imaging exposes people to small but cumulatively harmful risks, while magnetic resonance imaging is expensive.

Joslin's Kahn reckons there is a good possibility that brown fat may be present in significant amounts in more of the population, but it is not easily picked up by imaging.

But how much energy brown fat burns is an open question. In preliminary experiments by Joslin scientists, normal-weight people who sat in a 15-degree room for two hours wearing summer clothing chewed up 100 to 250 extra calories per day. An extra 250 calories burned daily for two weeks amounts to losing a pound of fat.

For now, your best bet to boosting brown fat could be braving the cold. Try going without extra layers on one of these chilly Hong Kong days. At 15 to 16 degrees, Wong estimates you could burn an extra 600 calories a day.

 

This article appeared in the South China Morning Post print edition as: Slim hopes
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