Researchers are exploring the potential benefits of brown adipose tissue – brown fat – in combating obesity. Brown fat generates heat and can improve insulin sensitivity and lipid clearance. New research on mice suggests that briefly exposing people to cold may stimulate their brown fat. However, the practicality and health implications of increasing brown fat remain uncertain. Although standing naked in the cold for 15 minutes may theoretically help, the metabolic demands of brown fat could be a double-edged sword. Building brown fat might be a metabolic challenge not to be taken lightly.
Some researchers think that building a different kind of fat might be just what the doctor ordered to help ward off obesity. It all comes down to how the body controls its temperature.
In mild weather, your liver largely maintains the body at 37°C. But if it is cold enough that your organs cannot keep up, a backup system kicks into gear – the body burns brown fat, or brown adipose tissue, a bank of bite-sized lipid packets that can be torched to elevate body temperature very quickly.
Higher levels of brown fat have been associated with increased sensitivity to insulin and enhanced lipid clearance, both of which are dampened in obesity. The hope is that purposefully building brown fat could help to improve people’s health outcomes.
Research on mice, published in Biochimie, suggests that people may be able to recruit brown adipose tissue by brief exposure to cold – but the benefits are uncertain.
What is brown fat? Do I want more of it?
White fat is used to store energy, but brown fat is fundamentally a heat-generating organ. It is the cellular break-glass-in-case-of-emergency of temperature regulation that is triggered right before you start to shiver, according to the Cleveland Clinic.
Brown fat takes its colour and name from an unusually high density of mitochondria – the power plants inside cells that convert sugar and fat into usable energy. But unlike other tissues, the mitochondria in brown fat use a special protein called thermogenin to make heat their final product rather than cellular energy.
For decades, scientists believed that people only had significant deposits of brown adipose tissue in infancy. Newborns cannot shiver – they have not developed the muscle tone yet – and lose significant heat through their enormous heads, so the 5% of their body weight dedicated to brown fat is essential to their survival.
But in the past 20 years, researchers have confirmed that most adults also sport brown fat, largely in their upper chest and in the neck surrounding the spinal column.
Barbara Cannon and Jan Nedergaard, both professors emeriti at the University of Stockholm’s Department of Molecular Biosciences and co-authors of the Biochimie article, have spent a combined century studying “brown adipose tissue, how it works, how the mitochondria work and what kind of significance it has for both animal and human health,” Nedergaard says.
Metabolically, brown fat is expensive, requiring lots of cellular energy to maintain. When animals spend time in the cold, their body seems to increase the investment in brown fat as an insurance policy against future cold exposure.
Previous studies suggest that brown fat improves insulin sensitivity and lipid clearance, and some scientists think that brown adipose tissue could help to prevent obesity, essentially by increasing the energy the body expends at rest.
“There is a lot of hype around it at the moment – that brown fat could be a means of resolving obesity problems,” Cannon says. “I think we are a little sceptical about this, to be straightforward. Is it realistic to be able to increase human brown fat to the extent that would be needed?”
Cannon and Nedergaard set out to determine what it would take for people to build brown adipose tissue. “If I want to have more brown fat, how much time should I then spend in the cold?” Nedergaard says.
Chilly labs and toasty mice
Since brown fat is a temperature-regulating organ, Nedergaard and Cannon needed to push someone outside their thermal comfort zone to study its formation and function. Scientifically, that optimal comfort zone is called thermoneutrality – the ambient temperature at which an organism is not expanding energy to maintain body temperature.
The thinking is that dipping below the thermoneutral point triggers the formation of brown fat. Convincing people to sign on to spend time in the cold can be quite difficult, so metabolic researchers often turn to mouse models.
But Nedergaard and Cannon contend that many metabolic research projects have had an important oversight – researchers have been unwittingly chilling their mice. Lab animals are normally housed at 18–20°C, and that may be a very comfortable temperature for a clothed human, but room temperature for people is very taxing for mice. A mouse at 18°C is expending energy similar to what a person without a jacket would expend in the winter, Cannon explains.
For this experiment, the researchers first had to warm up some mice. The team allowed 52 mice to hang out at their actual thermoneutral point – a balmy 30°C – for 6 weeks. Then they brought them on little excursions to lab temperature – the equivalent of a cold shock for them – every day for a month to see how it affected brown fat formation.
A molecular mystery
The researchers were surprised to find that even brief jaunts into the “cold” were enough to alter brown fat composition.
“We would think that growing the brown adipose tissue by just giving it a short time every day would be nearly impossible,” Nedergaard says. That is because brown fat is only stimulated to grow during cold exposure – once the animal warms back up to its thermoneutral point, that brown fat should begin to be dismantled.
With the experimental mice spending much more time in thermoneutrality than the cold, you would expect brown fat tissue to “just be level over time. And yet it isn’t,” Cannon says.
“A short, short time in the cold has a disproportionately large effect,” Nedergaard says. Just 15 minutes a day significantly increased protein density in the mice’s largest store of brown fat tissue between their shoulder blades. Thirty minutes a day was enough to increase UCP1 – a protein linked to non-shivering thermogenesis, or heat generation – 10-fold.
These effects were larger than expected for such brief cold exposure but are not enough to really change a person’s metabolism. Achieving a greater effect required a substantial jump in cold exposure. “Only the mice constantly at 18°C” – the mice that lived in the cold around the clock – “had significantly lower weight”, the authors wrote.
Somehow, the mice metabolically learned that they would need that brown adipose tissue tomorrow, she explains. Cannon and Nedergaard cannot explain how the mice could conserve brown fat, but it sure makes good sense – the mice would save themselves the cellular expense of rebuilding and demolishing it every day.
What does this mean for people?
Cannon and Nedergaard say that this should not be read as a mandate to crank down the office thermostat.
If you are trying to emulate their experimental mice, the equivalent cold exposure for you would not be standing outside in the (temperate or polar) winter for 15 minutes. It would be standing outside with no coat – or naked, for maximum effect – for 15 minutes. And that is a lot to ask.
Even if people could build reservoirs of brown fat big enough to really affect their metabolism, this would create a metabolic monster, Nedergaard emphasises. Brown adipose tissue is energy-hungry. Once you developed significant enough stores of brown fat to combat obesity, your whole body would have to go into overdrive to support it.
“You would have to eat twice as much every day, your heart would have to work twice as hard all the time, your lungs also, and so on,” Nedergaard says. “Keeping up this higher metabolism strongly affects practically all parameters in the body.”
