Supplement boost turns mice into fat-burning machines

As animals get older – be they mice or humans – they generally become more sensitive to cold conditions. It’s one of the reasons we have a Winter Fuel Payment for pensioners – as we age, we become more vulnerable to tough environmental conditions. A new study from the University of Utah has found that, in elderly mice at least, tolerance of the cold can be boosted through a simple nutritional supplement – and it may have a surprising knock on effect to obesity treatments.

The supplement in question – L-carnitine – boosted levels of a newly discovered source of brown fat in mice. Brown fat generates body heat in cold conditions, as distinct from white fat that simply stores calories.

The researchers made this discovery in a roundabout way. Their interest was first piqued when they noticed that mousey levels of a waxy lipid called acylcarnitines rose in young mice undergoing a change of temperature. By contrast, elderly mice’s acylcarnitine levels barely moved, as they struggled to keep their core temperature at a safe level. Lead author Judith Simcox was surprised to see acylcarnitines in the bloodstream: “The dogma was that once cells generated them, they used them right away.”

Indeed, generally speaking, high levels of acylcarnitines are viewed as bad news – it’s an indicator of a metabolic disease in infants, and they build up in the bloodstream during exercise where they are seen as a sign of muscles under stress. But here, in these chilly mice, a buildup of acylcarnitines appeared to be a good thing, resulting in raised levels of brown fat, subsequently used to keep the mice at a livable temperature.

The researchers traced the progress of the lipid, and discovered that they originated in the liver before making their way into the bloodstream and ending up as a number of energy-intensive tissues including brown fat. After this it was broken down and metabolised, suggesting that the lipid had been called upon specifically to generate heat and warm their mousey bodies. Sure enough, if the researchers reduced the lipids, even young mice lost their ability to effectively regulate their temperature.

“This work is putting a new face on an old character,” says Simcox. “We’re changing how we think about cold-induced thermogenesis.”

But why might older mice be worse at generating acylcarnitines than younger mice? Is it just a part of ageing, or reflective of their changed lifestyle?

“The lipids that we found are made the mitochondria, and it’s possible that with ageing this reflects impaired mitochondrial function,” Claudio Villanueva, Utah’s assistant professor of biochemistry and the senior author of the paper, tells me. “We know that there are a number of age-related diseases like Parkinson’s that result from impaired mitochondrial function.”

The human touch

It’s always worth being cautious about parallels drawn between mice and men. If everything that worked on mice worked on humans, we’d have a far larger range of medicines to choose from.

I asked Villanueva exactly how comparable mice are to humans in terms of cold tolerance. “We know that infants have brown fat and are highly reliant [on it] to maintain body temperature,” he explained. “There’s also evidence that adults have brown fat as well, and the amount varies from person to person. Individuals that are lean have more brown fat, while obese individuals are less likely to have it.

“Small mammals like rodents seem to rely more on brown fat for thermogenesis. We know less about mechanisms that maintain body temperature in humans, but our studies in mice will give us clues about pathways we should be studying in humans.”

In fact, the chief conclusion of the research isn’t that we can heat elderly humans in the same way as rodents: it’s that the discovery could help tackle obesity by triggering the burning of fat. According to Villanueva, humans have around 50g of brown fats on average – enough to burn around 200 calories per day. If these could be boosted in the same way, the loss of weight could be dramatic.

“In these studies, we looked at five hours of cold exposure without food, and during this period mice lose weight,” Villanueva explains. “The acylcarnitines are a way for the body to direct energy towards tissues that burn energy, like brown fat, heart and muscle. Understanding how mammals rev up metabolism to sustain their core body temperature in the cold may provide clues about how we may be able to target these pathways in humans to have a similar effect.”

It’s possible that, evolutionarily speaking, older mice are worse at heating themselves up because at their age it isn’t a wise use of energy. If that’s the case, triggering the same response in humans to deliberately burn calories is an interesting example of turning the body’s own natural defences to our advantage. Further study will be required to know for sure.

Image: Yu-Chan Chen used under Creative Commons

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