Mammals burn more energy to maintain their body temperature when exposed to cold temperatures, and this increase in energy expenditure triggers an increased appetite, but the specific mechanism controlling this response was not fully understood. This new study’s first author, Ye Lab postdoctoral research associate Neeraj Lal, Ph.D., describes the identification of a cluster of neurons that work like a switch for this cold-activated food-seeking 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,” says study senior author Li Ye, PhD, associate professor and the Abide-Vividion Chair in Chemistry and Chemical Biology at Scripps Research.
With the onset of cold temperatures, according to the researchers, the mice were observed to increase their food-seeking only after a delay of about 6 hours, suggesting the behavioral change may not be simply a direct result of cold sensing.
The researchers used whole-brain clearing and light sheet microscopy to compare the activity of neurons across the brain in cold and warm temperatures. This revealed that while most of the neuronal activity across the brain was much lower in the cold, portions of the thalamus showed higher activation.
The investigations zeroed in on the xiphoid nucleus of the midline thalamus, revealing that activity in these neurons spiked in cold conditions just before the animals stirred from their cold-induced lethargy to look for food. However, when food was less available the activity increased in the xiphoid nucleus was even greater suggesting that the neurons respond to a cold-induced energy deficit rather than the cold temperature itself.
When these neurons were artificially activated the mice increased their food-seeking but not other activities, and similarly, when they were inhibited the animals decreased food-seeking. The effects appeared only under cold conditions, suggesting that cold provides a separate signal that must also be present for appetite changes to occur.
Lastly, the researchers showed that xiphoid nucleus neurons project to the nucleus accumbens brain region which is known for its role in integrating reward/aversion signals to guide behavior, which includes feeding behaviors.
“One of our key goals now is to figure out how to decouple the appetite increase from the energy-expenditure increase,” says Ye. “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.”
