As we age, we become more sensitive to the cold.
As we age, our ability to keep warm as temperatures drop is compromised, leaving older individuals at risk of hyperthermia.
Recently, a study using aging mice – conducted at the University of Utah Health in Salt Lake City – investigated whether or not there was something that could be done to reduce this risk. Led by senior author Claudio Villanueva, Ph.D., an assistant professor of biochemistry, the team focused particularly on fats.
White fat accumulates when we take on too many calories, which puts us at risk of metabolic disease. Brown fat, however, is different; it is rich in mitochondria, and, as temperatures turn frosty, brown fat is activated to generate heat.
In human adults, there is little brown fat to be found. However, in newborns and other animals that need to brave the cold (such as mice), it is much more abundant.
Boosting older animals’ response to cold
Prof. Villanueva’s team were particularly interested in changes in acylcarnitines levels in the blood. Their study showed that this waxy lipid rose rapidly in response to lower temperatures, but in older mice, acylcarnitines remained relatively low – a possible sign that they had less control over their core temperature. These observations were not entirely expected.
“It was surprising to see acylcarnitines in the bloodstream. The dogma was that once cells generated them, they used them right away.”
Lead author Judith Simcox, Ph.D.
To investigate this further, the researchers gave older mice a single dose of the common nutritional supplement L-carnitine, which is known to increase levels of acylcarnitines.
The increased levels of circulating acylcarnitines improved the older mice’s ability to adapt to the cold.
These intriguing results are published this week in the journal Cell Metabolism.
Tracing acylcarnitines
Previously, when scientists saw circulating acylcarnitines, it was considered a sign of problems. For instance, in infants, higher levels of acylcarnitines indicated metabolic disease. Similarly, levels have been shown to escalate in the blood during exercise, signifying a muscle under duress.
The fact that the researchers measured an increase in this lipid as the temperatue dropped inferred that it may also be part of a healthy response. Dr. Simcox followed the trail of acylcarnitines and found that they were emanating from the liver. This is the first time that the liver has been implicated in cold adaptation.
From the liver, the lipids journeyed through the bloodstream and ended up in “energy-intensive tissues,” including brown fat. Upon arrival, brown fat broke down and metabolized the acylcarnitines, indicating that they are being used to generate heat.
To further investigate this relationship, the researchers artificially reduced the amount of circulating acylcarnitines. Once levels had been lowered, even younger mice struggled to warm up in cold temperatures.
Brown fat and obesity
If L-carnitine – a readily available and cost-effective supplement – could be useful for helping older adults to stave off hyperthermia, this would be a considerable breakthrough. Of course, there will need to be further testing.
The fact that humans have considerably less brown fat than mice is likely to be an important factor. However, it is not just older adults that might benefit from this new line of inquiry.
“This work is putting a new face on an old character,” says Dr. Simcox. “We’re changing how we think about cold-induced thermogenesis.”
Recently, there has been a lot of interest in brown fat and how it could potentially be used to combat obesity. Because it burns calories, it is thought that it might be able to burn excess fat.
As Prof. Villanueva explains, “The idea is to increase fuel utilization to drive the energy-demanding process of adapting to the cold. If we can find a way to tell the body to expend more energy than it is taking in, the calories lost can lead to weight loss.”
Until now, finding a way to activate brown fat has been a stumbling block. Now, with the knowledge that acylcarnitines might act as a switch, this avenue of investigation is likely to pick up pace.
