Neural Mechanisms Responsible for Cold-Induced Food Seeking Identified

Mammals automatically burn more energy to maintain normal body temperature when exposed to cold. This cold-activated increase in energy expenditure triggers an increase in appetite and feeding. In a new study, a team from Scripps Research identified the xiphoid nucleus of the midline thalamus as responsible for controlling this behavior in mice. 

“This is a fundamental adaptive mechanism in mammals and targeting it with future treatments might allow the enhancement of the metabolic benefits of cold or other forms of fat burning,” explained Li Ye, senior author of the study published in Nature.

Using whole-brain clearing and light sheet microscopy, the researchers compared the activity of neurons across the brain during cold versus warm conditions. They found that while most of the neuronal activity across the brain was much lower in the cold condition, portions of the thalamus showed higher activation.

Eventually, the team zeroed in on the xiphoid nucleus of the midline thalamus, showing that activity in these neurons spiked under cold conditions just before the mice stirred from their cold-induced torpor to look for food. When less food was available at the onset of the cold condition, the activity increase in the xiphoid nucleus was even greater—suggesting that these neurons respond to a cold-induced energy deficit rather than cold itself.

When the researchers artificially activated these neurons, the mice increased their food-seeking, but not other activities. Similarly, when the team inhibited the activity of these neurons, the mice decreased their food-seeking. These effects appeared only under the cold condition, implying that cold temperatures provide a separate signal that must also be present for appetite changes to occur.

In a last set of experiments, the team showed that these xiphoid nucleus neurons project to a brain region called the nucleus accumbens—an area long known for its role in integrating reward and aversion signals to guide behavior, including feeding behavior.

Ultimately, these results may have clinical relevance, Ye says, for they suggest the possibility of blocking the usual cold-induced appetite increase, allowing relatively simple cold exposure regimens to drive weight loss much more efficiently.

“One of our key goals now is to figure out how to decouple the appetite increase from the energy-expenditure increase,” he says. “We also want to find out if this cold-induced appetite-increase mechanism is part of a broader mechanism the body uses to compensate for extra energy expenditure, for example after exercise.”